Topic: Imaging

Abstract

Impact of heart rate on coronary computed tomographic angiography interpretability with a third-generation dual-source scanner.

Miller RJH, Eisenberg E, Friedman J, Cheng V, ... Thomson L, Berman DS
Background
Guidelines suggest coronary computed tomography angiography (CCTA) should be performed with a heart rate (HR) below 60. Third-generation dual-source CT (DSCT) scanners, with improved temporal resolution, and end-systolic acquisition may facilitate imaging at higher HRs. We determined the influence of HR and end-systolic acquisition on image interpretability and quality with a third-generation DSCT.
Methods
Patients who underwent CCTA between July 2017 and December 2018 were retrospectively identified. All images were acquired using a SOMATOM Force scanner (Siemens Healthcare). The primary outcome was the presence of any uninterpretable coronary segment. The association between HR and CCTA with uninterpretable segments was assessed with multivariable logistic regression, correcting for demographics and imaging variables.
Results
In total, 2620 patients were included, mean age 61.4 ± 12.9 years and 61.2% male, with uninterpretable segments present in 229 (8.7%) scans. In multivariable analysis, HR 80-89 was associated with an increased likelihood of having a scan with uninterpretable segments (adjusted odds ratio [OR] 4.53, p < 0.001). However, no significant association was present with end-systolic acquisition (HR 80-89, adjusted OR 2.32, p = 0.125). HR ≥ 90 was associated with a decreased likelihood of good or excellent image quality (adjusted OR 0.26, 95% CI 0.11-0.63, p = 0.003).
Conclusions
With third-generation dual-source CT scanners, patients with HR 60-80 can be imaged without impacting image interpretability. End-systolic image acquisition facilitates imaging at HRs > 80 without increasing non-diagnostic scans. Routine use of systolic gating could omit the need for strict HR control and pre-test beta blockade currently required for CCTA.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Nov 2019; 295:42-47
Miller RJH, Eisenberg E, Friedman J, Cheng V, ... Thomson L, Berman DS
Int J Cardiol: 14 Nov 2019; 295:42-47 | PMID: 31427117
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Abstract

Prognostic value of cardiac metaiodobenzylguanidine imaging and QRS duration in implantable cardioverter defibrillator patients with and without heart failure.

Kawasaki M, Yamada T, Morita T, Furukawa Y, ... Sakata Y, Fukunami M
Background
Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recent studies showed that the highest rate of ventricular tachyarrhythmias (VTs) is seen in HF patients with an intermediate decrease in MIBG uptake, rather than in those with the lowest values. However, prolonged QRS duration (QRSd) has been shown to be associated with VTs in HF patients. This study assessed the prognostic value of the combination of an intermediate decrease in MIBG uptake and prolonged QRSd for predicting VTs in patients with implantable cardioverter defibrillators (ICDs) in relation to the presence of heart failure (HF).
Methods and results
A total of 196 outpatients with ICDs (age: 64 ± 14 years, male: 81%, left ventricular ejection fraction [LVEF]: 49% ± 16%) were prospectively enrolled; 135 had HF (NYHA class: 2.0 ± 0.6). At entry, cardiac MIBG imaging was performed, and QRSd was measured on standard 12‑lead electrocardiography. An intermediate decrease in the heart-to-mediastinum ratio on the delayed planar image (ID-H/M) was defined as 1.40-1.89. During the 3.3 ± 2.2-year follow-up, 59 patients had appropriate ICD discharges (ATx) for VTs. On multivariate Cox analysis, ID-H/M and prolonged QRSd (≥147 ms) were significantly and independently associated with ATx. In both patients with and without HF, ATx were significantly more frequent in patients with ID-H/M and/or prolonged QRSd than in those with neither (with HF: 40% vs. 14%, p = 0.020; without HF: 43% vs. 10%, p = 0.0028).
Conclusions
The combination of ID-H/M and prolonged QRSd provided more prognostic information for predicting VTs in ICD patients, with and without HF.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:164-171
Kawasaki M, Yamada T, Morita T, Furukawa Y, ... Sakata Y, Fukunami M
Int J Cardiol: 30 Nov 2019; 296:164-171 | PMID: 31371118
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Abstract

Loss of Rubicon ameliorates doxorubicin-induced cardiotoxicity through enhancement of mitochondrial quality.

Liu X, Zhang S, An L, Wu J, ... He L, Zhu H
Background
The therapeutic potential of doxorubicin (DOX) is limited by cardiotoxicity. Rubicon is an inhibitory interacting partner of autophagy protein UVRAG. Currently, the role of Rubicon in DOX-induced cardiotoxicity is unknown. In this study, we test the hypothesis that loss of Rubicon attenuates DOX-induced cardiotoxicity.
Methods
A mouse model of acute DOX-induced cardiotoxicity was established by a single intraperitoneal injection of DOX at a dose of 20 mg/kg. Rubicon expression was detected by Western blot. Cardiac damage was determined by measuring activities of lactate dehydrogenase and myocardial muscle creatine kinase in the serum, cytoplasmic vacuolization, collagen deposition, ROS levels, ATP content and mitochondrial damage in the heart. Cardiac morphometry and function were assessed by echocardiography. Markers for autophagy, mitophagy and mitochondrial dynamics were evaluated by Western blot and real time reverse transcription polymerase chain reaction.
Results
Rubicon expression was reduced in the heart 16 h after DOX treatment. DOX induced accumulation of cytoplasmic vacuolization and collagen, increased serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, enhanced ROS levels, reduced ATP content, pronounced mitochondrial damage and greater left ventricular wall thickness in wild type mice, which were mitigated by Rubicon deficiency. Mechanistically, loss of Rubicon improved DOX-induced impairment of autophagic flux, Parkin-mediated mitophagy and mitochondrial fission and fusion in the heart.
Conclusions
Loss of Rubicon ameliorates DOX-induced cardiotoxicity through enhancement of mitochondrial quality by improving autophagic flux, mitophagy and mitochondrial dynamics. Rubicon is a potential molecular target for prevention and therapy of DOX cardiotoxicity.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:129-135
Liu X, Zhang S, An L, Wu J, ... He L, Zhu H
Int J Cardiol: 30 Nov 2019; 296:129-135 | PMID: 31439425
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Abstract

False-positive stress echocardiograms: Predictors and prognostic relevance.

Rachwan RJ, Mshelbwala FS, Dardari Z, Batal O
Background
Recent studies indicate that the pretest likelihood of significant coronary artery disease (CAD) (≥50% luminal stenosis) is over-estimated and that the frequency and severity of positive stress tests have been decreasing. This suggests an increased prevalence of false-positive (FP) stress tests. The aims of this retrospective study were to investigate the predictors of FP stress echocardiography (SE) and to compare the outcomes of patients with FP results to those with true-positive (TP) results.
Methods
Patients who underwent SE between 2013 and 2017 in a tertiary-care center were reviewed. Included were patients aged ≥40years who had cardiac catheterization (CC) within 1year of the index stress test. SE was considered FP if a new or worsening wall motion abnormality was present in the absence of significant corresponding CAD.
Results
Of the 5100 patients with SE, 1069 satisfied inclusion criteria. A total of 305 patients had positive SE results; of which 162 (53%) were FP. Logistic regression revealed that female gender (p=0.009), the absence of diabetes (p=0.03), the absence of a personal history of CAD (p=0.004), and lower stress WMSI (p=0.03) were independently associated with FP results. Patients with FP results on SE had similar all-cause mortality to those with TP results.
Conclusions
Accounting for predictors of FP findings on SE could improve the interpretation of SE results and limit the use of unnecessary CC. Furthermore, patients with FP results on SE could benefit from aggressive risk factor control and careful clinical follow-up.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:157-163
Rachwan RJ, Mshelbwala FS, Dardari Z, Batal O
Int J Cardiol: 30 Nov 2019; 296:157-163 | PMID: 31477317
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Abstract

Usefulness of dual imaging stress echocardiography for the diagnosis of coronary allograft vasculopathy in heart transplant recipients.

Pichel IÁ, Fernández Cimadevilla OC, de la Hera Galarza JM, Pasanisi E, ... Sicari R, Fernández MM
Background
Coronary allograft vasculopathy (CAV) is the main factor limiting long-term survival after cardiac transplantation. Dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve (CRF) of the left anterior descending artery (LAD) is a state-of-the-art methodology during dipyridamole stress echocardiography (DiSE). This study involving 74 heart transplanted patients has the purpose to assess the diagnostic value of dipyridamole stress echocardiography with evaluation of wall motion (WM) and Doppler-derived coronary flow reserve for the diagnosis of coronary allograft vasculopathy.
Methods and results
All patients underwent DiSE and coronary angiography. Moderate-severe CAV was defined according to International Society of Heart and Lung Transplant (ISHLT) recommended nomenclature for CAV, and CFR < 2 was considered to be impaired. Moderate-severe CAV was present in 11 patients. WM analysis revealed four patients (5%) with rest WM abnormalities. CFR analysis revealed that 40 (54%) individuals had an abnormal result. The combined evaluation of WM analysis and CFR resulted in a sensitivity of 72.7% (95% CI: 39.3 to 92.6%), a specificity of 49.2% (95% CI: 36.5 to 61.9%), a positive predictive value of 20% (95% CI: 9.6 to 36.1%), and negative predictive value of 91.1% (95% CI: 75.1 to 97.6%) for the diagnosis of CAV.
Conclusions
Our results support the inclusion of DiSE performance in Heart transplant follow up protocol. The addition of CFR evaluation offers valuable information to the angiography findings in the detection of CAV and could be helpful in selected patients to adjust the time and indications of coronary angiography.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:109-112
Pichel IÁ, Fernández Cimadevilla OC, de la Hera Galarza JM, Pasanisi E, ... Sicari R, Fernández MM
Int J Cardiol: 30 Nov 2019; 296:109-112 | PMID: 31324395
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Abstract

The prognostic value of biventricular long axis strain using standard cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

Yang F, Wang J, Li Y, Li W, ... Han Y, Chen Y
Background
Long axis strain (LAS) is a parameter derived from standard cardiovascular magnetic resonance imaging. However, the prognostic value of biventricular LAS in hypertrophic cardiomyopathy (HCM) is unknown.
Methods
Patients with HCM (n = 384) and healthy volunteers (n = 150) were included in the study. Left ventricular (LV)-LAS was defined as the percentage change in the length measured from the epicardial border of the LV apex to the midpoint of a line connecting the mitral annulus at end-systole and end-diastole. Right ventricular (RV)-LAS represented the percentage change of length between epicardial border of the LV apex to the midpoint of a line connecting the tricuspid annulus at end-systole and end-diastole. The primary endpoint was a combination of all-cause death and sudden cardiac death aborted by appropriate implantable cardioverter-defibrillator discharge and cardiopulmonary resuscitation after syncope. The secondary endpoint was a combination of the primary endpoint and hospitalization for congestive heart failure.
Results
Twenty-nine patients (7.6%) achieved the primary endpoint, and the secondary endpoint occurred in 66 (17.2%) patients. In multivariate Cox regression analysis, RV-LAS was an independent prognostic factor for the primary (hazard ratio (HR), 1.13) and secondary (HR, 1.11) endpoints. In the subgroup of patients with a normal RV ejection fraction (EF) (>45.0%, n = 345), impaired RV-LAS was associated with adverse outcomes and might add incremental prognostic value to RVEF and tricuspid annular plane systolic excursion (TAPSE) (p < 0.01).
Conclusions
RV-LAS is an independent predictor of adverse prognosis in HCM in addition to RVEF and TAPSE.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Oct 2019; 294:43-49
Yang F, Wang J, Li Y, Li W, ... Han Y, Chen Y
Int J Cardiol: 31 Oct 2019; 294:43-49 | PMID: 31405582
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Abstract

Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells.

Kavanagh DPJ, Lokman AB, Neag G, Colley A, Kalia N
Aims
Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating heart in vivo. Haematopoietic stem/progenitor cells (HSPCs) offer a potential therapy but little is known about their homing dynamics at a cellular level and whether they protect coronary microvessels. This study used intravital microscopy to image the anaesthetized mouse beating heart microcirculation following stabilization.
Methods and results
A 3D-printed stabilizer was attached to the ischaemia-reperfusion injured (IRI) beating heart. The kinetics of neutrophil, platelet and HSPC recruitment, as well as functional capillary density (FCD), was imaged post-reperfusion. Laser speckle contrast imaging (LSCI) was used for the first time to monitor ventricular blood flow in beating hearts. Sustained hyperaemic responses were measured throughout reperfusion, initially indicating adequate flow resumption. Intravital microscopy confirmed large vessel perfusion but demonstrated poor transmission of flow to downstream coronary microvessels. Significant neutrophil adhesion and microthrombus formation occurred within capillaries with the latter occluding them, resulting in patchy perfusion and reduced FCD. Interestingly, \'patrolling\' neutrophils were also observed in capillaries. Haematopoietic stem/progenitor cells readily trafficked through the heart but local retention was poor. Despite this, remarkable anti-thromboinflammatory effects were observed, consequently improving microvascular perfusion.
Conclusion
We present a novel approach for imaging multiple microcirculatory perturbations in the beating heart with LSCI assessment of blood flow. Despite deceptive hyperaemic responses, increased microcirculatory flow heterogeneity was seen, with non-perfused areas interspersed with perfused areas. Microthrombi, rather than neutrophils, appeared to be the major causative factor. We further applied this technique to demonstrate local stem cell presence is not a pre-requisite to confer vasculoprotection. This is the first detailed in vivo characterization of coronary microcirculatory responses post-reperfusion injury.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Cardiovasc Res: 31 Oct 2019; 115:1918-1932
Kavanagh DPJ, Lokman AB, Neag G, Colley A, Kalia N
Cardiovasc Res: 31 Oct 2019; 115:1918-1932 | PMID: 31062860
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Abstract

Functional, Anatomical, and Prognostic Correlates of Coronary Flow Velocity Reserve During Stress Echocardiography.

Ciampi Q, Zagatina A, Cortigiani L, Gaibazzi N, ... Picano E,
Background
The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA).
Objectives
The purpose of this study was to assess the feasibility and functional correlates of CFVR.
Methods
This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up.
Results
The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome.
Conclusions
CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Nov 2019; 74:2278-2291
Ciampi Q, Zagatina A, Cortigiani L, Gaibazzi N, ... Picano E,
J Am Coll Cardiol: 04 Nov 2019; 74:2278-2291 | PMID: 31672185
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Abstract

Distinct Subgroups in Hypertrophic Cardiomyopathy in the NHLBI HCM Registry.

Neubauer S, Kolm P, Ho CY, Kwong RY, ... Kramer CM,
Background
The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.
Objectives
The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.
Methods
Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.
Results
A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.
Conclusions
The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 11 Nov 2019; 74:2333-2345
Neubauer S, Kolm P, Ho CY, Kwong RY, ... Kramer CM,
J Am Coll Cardiol: 11 Nov 2019; 74:2333-2345 | PMID: 31699273
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Abstract

Atrial fibrillation and cardiac fibrosis.

Sohns C, Marrouche NF

The understanding of atrial fibrillation (AF) evolved from a sole rhythm disturbance towards the complex concept of a cardiomyopathy based on arrhythmia substrates. There is evidence that atrial fibrosis can be visualized using late gadolinium enhancement cardiac magnetic resonance imaging and that it is a powerful predictor for the outcome of AF interventions. However, a strategy of an individual and fibrosis guided management of AF looks promising but results from prospective multicentre trials are pending. This review gives an overview about the relationship between cardiac fibrosis and AF focusing on translational aspects, clinical observations, and fibrosis imaging to emphasize the concept of personalized paths in AF management taking into account the individual amount and distribution of fibrosis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur Heart J: 11 Nov 2019; epub ahead of print
Sohns C, Marrouche NF
Eur Heart J: 11 Nov 2019; epub ahead of print | PMID: 31713590
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Abstract

Initial Imaging-Guided Strategy Versus Routine Care in Patients With Non-ST-Segment Elevation Myocardial Infarction.

Smulders MW, Kietselaer BLJH, Wildberger JE, Dagnelie PC, ... Crijns HJGM, Bekkers SCAM
Background
Patients with non-ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have obstructive coronary artery disease.
Objectives
This study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA.
Methods
This randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively.
Results
The CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% [p = 0.001], 66% [p < 0.001], and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 [95% confidence interval: 0.37 to 1.61]; CTA vs. routine, 0.66 [95% confidence interval: 0.31 to 1.42]; and CMR vs. CTA, 1.19 [95% confidence interval: 0.53 to 2.66]). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001).
Conclusions
A novel strategy of implementing CMR or CTA first in the diagnostic process in non-ST-segment elevation myocardial infarction is a safe gatekeeper for ICA.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Nov 2019; 74:2466-2477
Smulders MW, Kietselaer BLJH, Wildberger JE, Dagnelie PC, ... Crijns HJGM, Bekkers SCAM
J Am Coll Cardiol: 18 Nov 2019; 74:2466-2477 | PMID: 31727284
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Abstract

Predictors of Progression in Patients With Stage B Aortic Regurgitation.

Yang LT, Enriquez-Sarano M, Michelena HI, Nkomo VT, ... Wajih Ullah M, Pellikka PA
Background
The natural history of stage B aortic regurgitation (AR) is unknown.
Objectives
This study sought to examine determinants, rate, and consequences of progression of AR.
Methods
Consecutive patients with ≤moderate chronic AR quantified by effective regurgitant orifice area (EROA) and regurgitant volume (RVol) from 2004 to 2017 who had ≥1 subsequent echocardiogram with quantitation were included.
Results
Of 1,077 patients (66 ± 15 years of age), baseline trivial/mild AR was noted in 196 (18%), mild-to-moderate AR in 465 (43%), and moderate AR in 416 (39%); 10-year incidence of progression to ≥moderate-severe AR (stage C/D; progressors) was 12%, 30%, and 53%, respectively. At 4.1-year follow-up (interquartile range: 2.1 to 7.2 years), there were 228 progressors (21%), whose annualized progression rates within 3 years before diagnosis of ≥moderate-severe AR were 4.2 mm/year for EROA and 9.9 ml/year for RVol. Baseline AR severity and dimensions of sinotubular junction and annulus were associated with progression (all p ≤ 0.007); hypertension and systolic blood pressure were not. Progressors had faster chamber remodeling, functional class decline, and more aortic valve/aortic surgery. At medium-term follow-up, 242 patients (22%) died; poor survival was linked to age, comorbidities, functional class, resting heart rate, and left ventricular (LV) ejection fraction (p ≤ 0.003), not LV end-systolic dimension index. Survival after progression to stage C/D AR was associated with LV end-systolic dimension index (adjusted p = 0.02).
Conclusions
Progression from stage B to stage C/D AR was observed in 21% patients. Repeat echocardiography for trivial/mild, mild-to-moderate, and moderate AR at every 5, 3, and 1 years, respectively, was reasonable. EROA, RVol, annulus, and sinotubular junction should be routinely measured to estimate progression rates and identify patients at high risk of progression, which was associated with adverse consequences.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Nov 2019; 74:2480-2492
Yang LT, Enriquez-Sarano M, Michelena HI, Nkomo VT, ... Wajih Ullah M, Pellikka PA
J Am Coll Cardiol: 18 Nov 2019; 74:2480-2492 | PMID: 31727286
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Abstract

Evaluation, Management, and Outcomes of Patients Poorly Responsive to Cardiac Resynchronization Device Therapy.

Varma N, Boehmer J, Bhargava K, Yoo D, ... Gill J, Auricchio A
Background
\"Nonresponse\" to cardiac resynchronization therapy (CRT) is recognized, but definition(s) applied in practice, treatment(s), and their consequences are little known.
Objectives
The authors sought to assess nonresponse in the prospective, international, ADVANCE CRT registry (Advance Cardiac Resynchronization Therapy Registry).
Methods
Each subject\'s response was assessed at 6 months post-implantation using site-specific definitions and compared with the independently derived clinical composite score (CCS). Treatment(s) and hospitalization(s) were tracked during the following 6 months.
Results
Of 1,524 subjects enrolled in 69 centers (68 ± 12 years of age, 32% female, ischemic disease 39%), 74.3% received CRT-defibrillator devices, using mainly quadripolar LV leads (75%) deployed laterally (78%). Indications for CRT were wider than past trials. Among 1,327 evaluable subjects, site-defined nonresponse was 20.0% (greater age, comorbidities, ischemic cardiomyopathy, non-left bundle branch block, and lower %CRT pacing vs. responders). Site definitions used mainly clinical criteria (echocardiography infrequently), and underestimated nonresponders by 35% compared with CCS (58% sensitivity vs. CCS). Overall, more site-defined nonresponders received treatment (55.9% vs. 38.3% of responders; p < 0.001) using medication changes and heart failure education, but device programming less frequently. Intensification of in-clinic/remote evaluations and involvement of heart failure specialists remained minimal. Remarkably, 44% of site-defined nonresponders received no additional treatment. Frequency and duration of hospitalizations, and death, among site-defined nonresponders was significantly higher than responders.
Conclusions
A high incidence of CRT nonresponders persists despite good patient selection and LV lead position, but site identification methods have modest sensitivity. Following diagnosis, nonresponders are often passively managed, without specialty care, with poor outcome. ADVANCE CRT exposes a vulnerable group of heart failure patients. (Advance Cardiac Resynchronization Therapy Registry [ADVANCE CRT]; NCT01805154).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Nov 2019; epub ahead of print
Varma N, Boehmer J, Bhargava K, Yoo D, ... Gill J, Auricchio A
J Am Coll Cardiol: 05 Nov 2019; epub ahead of print | PMID: 31748196
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Impact:
Abstract

Multimodality Imaging in Infective Endocarditis: An Imaging Team Within the Endocarditis Team.

Erba PA, Pizzi MN, Roque A, Salaun E, ... Tornos P, Habib G

Infective endocarditis (IE) is a complex disease with cardiac involvement and multiorgan complications. Its prognosis depends on prompt diagnosis that leads to an aggressive therapeutic management combining antibiotic therapy and early cardiac surgery when indicated. However, IE diagnosis always poses a challenge, and echocardiography remains diagnostically imperfect in cases of prosthetic valve IE or cardiac implantable electronic device infection. In recent years, other imaging modalities (computed tomography, magnetic resonance imaging, nuclear imaging) have experienced significant technical improvements, and their application to the detection of cardiac and extracardiac IE-related lesions seems to be a strategic way forward in the management of patients with suspected IE. However, the scientific evidence in the literature remains limited; current guidelines address the use of the multimodality imaging in the field of IE with caution; the incremental value of each technique and their combinations is debated; and their use varies across countries. Despite these limitations, healthcare providers and surgeons should be aware of the possibilities offered by the multimodal imaging approach when appropriate. Here, we emphasize the value of a multidisciplinary heart valve team, the endocarditis team, underlining the importance of cardiac and extracardiac imaging experts in playing a key role in informing the diagnosis and management of patients with IE. Illustrative cases, critical appraisal of contemporary data, and conceptual and practical suggestions for clinicians that may help to improve the prognosis of patients with IE are provided in this review article.



Circulation: 18 Nov 2019; 140:1753-1765
Erba PA, Pizzi MN, Roque A, Salaun E, ... Tornos P, Habib G
Circulation: 18 Nov 2019; 140:1753-1765 | PMID: 31738598
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Impact:
Abstract

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management.

Al-Hussaini A, Abdelaty AMSEK, Gulsin GS, Arnold JR, ... McCann GP, Adlam D
Aims
To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury.
Methods and results
One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case-control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P <0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0-30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age <75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score >4 were associated with larger infarcts [>10% left ventricular (LV) mass].
Conclusion
The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 02 Jan 2020; epub ahead of print
Al-Hussaini A, Abdelaty AMSEK, Gulsin GS, Arnold JR, ... McCann GP, Adlam D
Eur Heart J: 02 Jan 2020; epub ahead of print | PMID: 31898721
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Impact:
Abstract

Incident Heart Failure and Long-Term Risk for Venous Thromboembolism.

Fanola CL, Norby FL, Shah AM, Chang PP, ... Cushman M, Folsom AR
Background
Heart failure (HF) hospitalization places patients at increased short-term risk for venous thromboembolism (VTE). Long-term risk for VTE associated with incident HF, HF subtypes, or structural heart disease is unknown.
Objectives
In the ARIC (Atherosclerosis Risk In Communities) cohort, VTE risk associated with incident HF, HF subtypes, and abnormal echocardiographic measures in the absence of clinical HF was assessed.
Methods
During follow-up, ARIC identified incident HF and subcategorized HF with preserved ejection fraction or reduced ejection fraction. At the fifth clinical examination, echocardiography was performed. Physicians adjudicated incident VTE using hospital records. Adjusted Cox proportional hazards models were used to evaluate the association between HF or echocardiographic exposures and VTE.
Results
Over a mean of 22 years in 13,728 subjects, of whom 2,696 (20%) developed incident HF, 729 subsequent VTE events were identified. HF was associated with increased long-term risk for VTE (adjusted hazard ratio: 3.13; 95% confidence interval: 2.58 to 3.80). In 7,588 subjects followed for a mean of 10 years, the risk for VTE was similar for HF with preserved ejection fraction (adjusted hazard ratio: 4.71; 95% CI: 2.94 to 7.52) and HF with reduced ejection fraction (adjusted hazard ratio: 5.53; 95% confidence interval: 3.42 to 8.94). In 5,438 subjects without HF followed for a mean of 3.5 years, left ventricular relative wall thickness and mean left ventricular wall thickness were independent predictors of VTE.
Conclusions
In this prospective population-based study, incident hospitalized HF (including both heart failure with preserved ejection fraction and reduced ejection fraction), as well as echocardiographic indicators of left ventricular remodeling, were associated with greatly increased risk for VTE, which persisted through long-term follow-up. Evidence-based strategies to prevent long-term VTE in patients with HF, beyond time of hospitalization, are needed.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 20 Jan 2020; 75:148-158
Fanola CL, Norby FL, Shah AM, Chang PP, ... Cushman M, Folsom AR
J Am Coll Cardiol: 20 Jan 2020; 75:148-158 | PMID: 31948643
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Abstract

Atrial Failure as a Clinical Entity: JACC Review Topic of the Week.

Bisbal F, Baranchuk A, Braunwald E, Bayés de Luna A, Bayés-Genís A

Atrial dysfunction has been widely considered a marker or consequence of other cardiac conditions rather than the cause itself. Here, we propose the term atrial failure as a clinically relevant entity, defined as any atrial dysfunction causing impaired heart performance, symptoms, and worsening quality of life or life expectancy. Aspects of the etiology, mechanisms, and consequences of atrial failure are discussed. Recent advances in cardiac electrophysiology and imaging have improved our understanding of the highly complex atrial anatomy and function, underlying the paramount importance of the atria in optimal heart performance. It is time to reappraise the concept of the failing atrium as a primary cause or aggravating factor of the symptoms in many of our patients. The concept of atrial failure may foster basic and translational research to gain a better understanding of how to identify and manage atrial dysfunction.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 20 Jan 2020; 75:222-232
Bisbal F, Baranchuk A, Braunwald E, Bayés de Luna A, Bayés-Genís A
J Am Coll Cardiol: 20 Jan 2020; 75:222-232 | PMID: 31948652
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Abstract

Increased Myocardial Stiffness in Patients with High Risk Left Ventricular Hypertrophy: The Hallmark of Stage-B HFpEF.

Hieda M, Sarma S, Hearon CM, Dias KA, ... Howden E, Levine BD

Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle-age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated LV myocardial stiffness when compared to healthy controls as a key marker for future HFpEF.Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers [NT-proBNP (>40 pg/ml) or TnT (>0.6 pg/ml)] were recruited, along with 61 age- and sexmatched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3D-echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion.There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (e.g., PCWP: LVH: 13.4 ± 2.7, vs. control: 11.7 ± 1.7mmHg, P<0.0001). The LV was less distensible in LVH than controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (PCWP - RAP), LV myocardial stiffness was nearly 30% greater in LVH compared to controls (LVH stiffness constant: 0.053 ± 0.027, vs. controls: 0.042 ± 0.020, P=0.028).LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than age- and sex- matched controls, and thus appears to represent a transitional state from a \"normal healthy-heart\" to HFpEF. Although, LV myocardial stiffness of LVH patients is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high risk individuals.URL: https://clinicaltrials.gov Unique Identifiers: NCT03476785 and NCT02039154.



Circulation: 22 Dec 2019; epub ahead of print
Hieda M, Sarma S, Hearon CM, Dias KA, ... Howden E, Levine BD
Circulation: 22 Dec 2019; epub ahead of print | PMID: 31865771
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Abstract

Staging Cardiac Damage in Patients With Hypertension.

Seko Y, Kato T, Shiba M, Morita Y, ... Haruna T, Inoko M

Ventricular and extraventricular response to pressure overload may be a common process in aortic stenosis and hypertension. We aimed to evaluate the association of a newly defined staging classification characterizing the extent of cardiac damage, originally developed for aortic stenosis, with long-term outcomes in patients with hypertension. We retrospectively analyzed 1639 patients with hypertension who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a Japanese hospital, after excluding severe and moderate aortic stenosis, aortic regurgitation, mitral stenosis, previous myocardial infarction, or cardiomyopathy. We classified patients according to the presence or absence of cardiac damage as detected on echocardiography as follows: stage 0, no cardiac damage (n=858; 52.3%); stage 1, left ventricular damage (n=358; 21.8%); stage 2, left atrial or mitral valve damage (n=360; 22.0%); or stage 3 and 4, pulmonary vasculature, tricuspid valve, or right ventricular damage (n=63; 3.8%). The primary outcome was a composite of all-cause death and major adverse cardiac events. Cumulative 3-year incidence of the primary outcome was 15.5% in stage 0, 20.7% in stage 1, 31.8% in stage 2, and 60.6% in stage 3. After adjusting for confounders, the stage was incrementally associated with higher risk of the primary outcome (per 1-stage increase: hazard ratio, 1.46 [95% CI, 1.31-1.61]; <0.001). The staging classification characterizing the extent of cardiac damage, originally developed for aortic stenosis, was associated with long-term outcomes in patients with hypertension in a stepwise manner.



Hypertension: 03 Nov 2019:HYPERTENSIONAHA11913797; epub ahead of print
Seko Y, Kato T, Shiba M, Morita Y, ... Haruna T, Inoko M
Hypertension: 03 Nov 2019:HYPERTENSIONAHA11913797; epub ahead of print | PMID: 31679419
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Abstract

Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction.

Ford TJ, Corcoran D, Padmanabhan S, Aman A, ... Davenport AP, Berry C
Aims
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide linked to vascular diseases through a common intronic gene enhancer [(rs9349379-G allele), chromosome 6 (PHACTR1/EDN1)]. We performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD).
Methods and results
Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects [allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P = 0.013]. The G allele was associated with higher plasma serum ET-1 [least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10-0.53; P = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10-4.96; P = 0.027]. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P = 0.042) and exercise testing (N = 87; -3.0 units in Duke Exercise Treadmill Score; -5.8 to -0.1; P = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status.
Conclusion
We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina.
Trial registration
ClinicalTrials.gov: NCT03193294.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J: 22 Jan 2020; epub ahead of print
Ford TJ, Corcoran D, Padmanabhan S, Aman A, ... Davenport AP, Berry C
Eur Heart J: 22 Jan 2020; epub ahead of print | PMID: 31972008
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Abstract

OUTSMART HF: A Randomized Controlled Trial of Routine Versus Selective Cardiac Magnetic Resonance for Patients with Non-Ischemic Heart Failure (IMAGE-HF 1B).

Paterson DI, Wells G, Erthal F, Mielniczuk L, ... Chan KL,

Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF), however there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Hypothesis: Routine use of CMR will yield more specific diagnoses in non-ischemic HF. Secondary hypothesis: Routine use of CMR will improve patient outcomes.Patients with non-ischemic HF were randomized to Routine versus Selective CMR. Patients in the Routine strategy underwent echo and CMR whereas those assigned to Selective use underwent echo with or without CMR according to the clinical presentation. HF etiology was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months.500 patients (344 male), mean age 59±13, were randomized. The Routine and Selective CMR strategies had similar rates of specific HF etiologies at 3 months clinical follow-up, 44% vs. 50% respectively, p=0.22. At image interpretation, rates of specific HF etiology were also not different between Routine and Selective CMR, 34% vs. 30% respectively, p=0.34. However, 24% of patients in the Selective group underwent a non-protocol CMR. Patients with specific HF etiologies had more clinical events than those with non-specific etiologies based on imaging classification, 19% vs. 12% respectively, p=0.02, but not on clinical assessment, 15% vs. 14%, p=0.49.In patients with non-ischemic HF, Routine CMR does not yield more specific HF etiologies on clinical assessment. Patients with specific HF etiologies from imaging had worse outcomes whereas HF etiologies defined clinically did not.URL: https://clinicaltrials.gov. Unique Identifier: NCT01281384.



Circulation: 07 Jan 2020; epub ahead of print
Paterson DI, Wells G, Erthal F, Mielniczuk L, ... Chan KL,
Circulation: 07 Jan 2020; epub ahead of print | PMID: 31910649
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Abstract

Cytokine mRNA Degradation in Cardiomyocytes Restrains Sterile Inflammation in Pressure Overloaded Hearts.

Omiya S, Omori Y, Taneike M, Murakawa T, ... Akira S, Otsu K

Proinflammatory cytokines play an important role in the pathogenesis of heart failure. However, the mechanisms responsible for maintaining sterile inflammation within failing hearts remain poorly defined. Although transcriptional control is important for proinflammatory cytokine gene expression, the stability of the mRNA also contributes to the kinetics of immune responses. Regnase-1 is an RNase involved in the degradation of a set of proinflammatory cytokine mRNAs in immune cells. The role of Regnase-1 in non-immune cells such as cardiomyocytes remains to be elucidated.To examine the role of proinflammatory cytokine degradation by Regnase-1 in cardiomyocytes, cardiomyocyte-specific Regnase-1-deficient mice were generated. The mice were subjected to pressure overload by means of transverse aortic constriction (TAC) to induce heart failure. Cardiac remodeling was assessed by echocardiography as well as histological and molecular analyses 4 weeks after operation. Inflammatory cell infiltration was examined by immunostaining. Furthermore, interleukin-6 (IL-6) signaling was inhibited by the administration with its receptor antibody. Finally, overexpression of Regnase-1 in the heart was performed by adeno-associated viral vector-mediated gene transfer.Cardiomyocyte-specific Regnase-1-deficient mice showed no cardiac phenotypes under baseline conditions, but exhibited severe inflammation and dilated cardiomyopathy after 4 weeks of pressure overload compared to the control littermates. Four weeks after TAC, themRNA level was upregulated, but not other cytokine mRNAs including tumor necrosis factor-α in Regnase-1-deficient hearts. Although themRNA level increased 1 week after operation in both Regnase-1-deficient and control hearts, it showed no increase in control hearts 4 weeks after operation. Administration of anti-IL-6 receptor antibody attenuated the development of inflammation and cardiomyopathy in cardiomyocyte-specific Regnase-1-deficient mice. In severe pressure overloaded wild-type mouse hearts, sustained induction ofmRNA was observed, even though the protein level of Regnase-1 increased. Adeno-associated virus 9- mediated cardiomyocyte-targeted gene delivery of Regnase-1 or administration of anti-IL-6 receptor antibody attenuated the development of cardiomyopathy induced by severe pressure overload in wild-type mice.The degradation of cytokine mRNA by Regnase-1 in cardiomyocytes plays an important role in restraining sterile inflammation in failing hearts and the Regnase-1-mediated pathway might be a therapeutic target to treat patients with heart failure.



Circulation: 13 Jan 2020; epub ahead of print
Omiya S, Omori Y, Taneike M, Murakawa T, ... Akira S, Otsu K
Circulation: 13 Jan 2020; epub ahead of print | PMID: 31931613
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Abstract

Neutrophil-Derived S100A8/A9 Amplify Granulopoiesis Following Myocardial Infarction.

Sreejit G, Abdel-Latif A, Athmanathan B, Annabathula R, ... Murphy AJ, Nagareddy PR

Myocardial infarction (MI) triggers myelopoiesis resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.Using a mouse model of the permanent ligation of the left anterior descending (LAD) artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of acute inflammatory response and the underlying signaling pathways. Utilizing a combination of genetic and pharmacological strategies, we identified the sequalae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indices of neutrophilia with major adverse cardiovascular events (MACE) was studied in a cohort of acute MI patients.Induction of MI resulted in a rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll Like Receptor (TLR) 4 and prime the Nod Like Receptor (NLR) family Pyrin Domain-Containing 3 (Nlrp3) inflammasome in naïve neutrophils and promote interleukin 1 (IL-1β) secretion. The released IL-1β interact with its receptor (Interleukin 1 Receptor Type 1, IL1R1) on hematopoietic stem and progenitor cells in the bone marrow (BM), and stimulate granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and its downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome (ACS), higher neutrophil count on admission and post-revascularization correlates positively with major adverse cardiovascular disease (CVD) outcomes.Our study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response following myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or its downstream mediators (e.g. Nlrp3, IL-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in ACS patients.



Circulation: 15 Jan 2020; epub ahead of print
Sreejit G, Abdel-Latif A, Athmanathan B, Annabathula R, ... Murphy AJ, Nagareddy PR
Circulation: 15 Jan 2020; epub ahead of print | PMID: 31941367
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Abstract

Investigation and Treatment of High Blood Pressure in Young People: Too Much Medicine or Appropriate Risk Reduction?

Hinton TC, Adams ZH, Baker RP, Hope KA, ... Hart EC, Nightingale AK

Hypertension among young people is common, affecting 1 in 8 adults aged between 20 and 40 years. This number is likely to increase with lifestyle behaviors and lowering of hypertension diagnostic thresholds. Early-life factors influence blood pressure (BP) although the mechanisms are unclear; BP tracks strongly within individuals from adolescence through to later life. Higher BP at a young age is associated with abnormalities on heart and brain imaging and increases the likelihood of cardiovascular events by middle age. However, diagnosis rates are lower, and treatment is often delayed in young people. This reflects the lack of high-quality evidence that lowering BP in young adults improves cardiovascular outcomes later in life. In this review, we evaluate the current evidence regarding the association between BP in young adult life and adverse cardiovascular outcomes later in life. Following this, we discuss which young people with raised BP should be investigated for secondary causes of hypertension. Third, we assess the current models to assess cardiovascular risk and show a lack of validation in the younger age group. Fourth, we evaluate the evidence for lifestyle interventions in this age group and demonstrate a lack of persistence in BP lowering once the initial intervention has been delivered. Fifth, we address the pros and cons of drug treatment for raised BP in young people. Finally, there are unique life events in young people, such as pregnancy, that require specific advice on management and treatment of BP.



Hypertension: 17 Nov 2019:HYPERTENSIONAHA11913820; epub ahead of print
Hinton TC, Adams ZH, Baker RP, Hope KA, ... Hart EC, Nightingale AK
Hypertension: 17 Nov 2019:HYPERTENSIONAHA11913820; epub ahead of print | PMID: 31735086
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Abstract

Statins Reverse Postpartum Cardiovascular Dysfunction in a Rat Model of Preeclampsia.

Kräker K, O\'Driscoll JM, Schütte T, Herse F, ... Dechend R, Haase N

Preeclampsia is associated with increased cardiovascular long-term risk; however, the underlying functional and structural mechanisms are unknown. We investigated maternal cardiac alterations after preeclampsia. Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] develop a preeclamptic phenotype with hypertension and albuminuria during pregnancy when mated with male rats bearing the human renin gene [TGR(hRen)L10J] but behave physiologically normal before and after pregnancy. Furthermore, rats were treated with pravastatin. We tested the hypothesis that statins are a potential therapeutic intervention to reduce cardiovascular alterations due to simulated preeclamptic pregnancy. Although hypertension persists for only 8 days in pregnancy, former preeclampsia rats exhibit significant cardiac hypertrophy 28 days after pregnancy observed in both speckle tracking echocardiography and histological staining. In addition, fibrosis and capillary rarefaction was evident. Pravastatin treatment ameliorated the remodeling and improved cardiac output postpartum. Preeclamptic pregnancy induces irreversible structural changes of cardiac hypertrophy and fibrosis, which can be moderated by pravastatin treatment. This pathological cardiac remodeling might be involved in increased cardiovascular risk in later life.



Hypertension: 01 Dec 2019:HYPERTENSIONAHA11913219; epub ahead of print
Kräker K, O'Driscoll JM, Schütte T, Herse F, ... Dechend R, Haase N
Hypertension: 01 Dec 2019:HYPERTENSIONAHA11913219; epub ahead of print | PMID: 31786987
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Abstract

Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

Walter J, du Fay de Lavallaz J, Koechlin L, Zimmermann T, ... Reichlin T, Mueller C
Background
The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown.
Objective
To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD.
Design
Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148).
Setting
University hospital.
Patients
1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia.
Measurements
Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L).
Results
Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%).
Limitation
Data were generated in a large single-center diagnostic study using central adjudication.
Conclusion
In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia.
Primary funding source
European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.



Ann Intern Med: 06 Jan 2020; epub ahead of print
Walter J, du Fay de Lavallaz J, Koechlin L, Zimmermann T, ... Reichlin T, Mueller C
Ann Intern Med: 06 Jan 2020; epub ahead of print | PMID: 31905377
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Abstract

Frequent Cognitive Impairment in Patients With Disorders Along the Heart-Brain Axis.

Hooghiemstra AM, Leeuwis AE, Bertens AS, Biessels GJ, ... , van der Flier WM

Background and Purpose- Patients with cardiovascular disease are at increased risk for cognitive decline. We studied the occurrence and profile of cognitive impairment in 3 patient groups as exemplar conditions of hemodynamic disturbances at different levels of the heart-brain axis, including patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (possible vascular cognitive impairment [VCI]). Methods- In 555 participants (160 HF, 107 COD, 160 possible VCI, 128 reference participants; 68±9 years; 36% F; Mini-Mental State Examination 28±2), we assessed cognitive functioning with a comprehensive test battery. Test scores were transformed into -scores. Compound -scores were constructed for: memory, language, attention/psychomotor speed, executive functioning, and global cognitive functioning. We rated cognitive domains as impaired when -score≤-1.5. Based on the number of impaired domains, patients were classified as cognitively normal, minor, or major cognitive impairment. We used general linear models and χ tests to compare cognitive functioning between patient groups and the reference group. Results- Age, sex, and education adjusted global cognitive functioning z-score was lower in patients with COD (β [SE]=-0.46 [0.10], <0.001) and possible VCI (β [SE]=-0.80 [0.09], 0.001) compared with reference participants. On all domains, -scores were lower in patients with COD and possible VCI compared with reference participants. Patients with HF had lower z-scores on attention/speed and language compared with reference participants. Cognitive impairment was observed in 18% of HF, 36% of COD, and 45% possible VCI. There was no difference in profile of impaired cognitive domains between patient groups. Memory and attention-psychomotor speed were most commonly affected, followed by executive functioning and language. Conclusions- A substantial part of patients with HF and COD had cognitive impairment, which warrants vigilance for the occurrence of cognitive impairment. These results underline the importance of an integrative approach in medicine in patients presenting with disorders in the heart-brain axis.



Stroke: 04 Nov 2019:STROKEAHA119026031; epub ahead of print
Hooghiemstra AM, Leeuwis AE, Bertens AS, Biessels GJ, ... , van der Flier WM
Stroke: 04 Nov 2019:STROKEAHA119026031; epub ahead of print | PMID: 31684846
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Abstract

Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy.

Kuster DWD, Lynch TL, Barefield DY, Sivaguru M, ... Namakkal-Soorappan R, Sadayappan S
Aims
A 25-base pair deletion in the cardiac myosin binding protein-C (cMyBP-C) gene (MYBPC3), proposed to skip exon 33, modifies the C10 domain (cMyBP-CΔC10mut) and is associated with hypertrophic cardiomyopathy (HCM) and heart failure, affecting approximately 100 million South Asians. However, the molecular mechanisms underlying the pathogenicity of cMyBP-CΔC10mutin vivo are unknown. We hypothesized that expression of cMyBP-CΔC10mut exerts a poison polypeptide effect leading to improper assembly of cardiac sarcomeres and the development of HCM.
Methods and results
To determine whether expression of cMyBP-CΔC10mut is sufficient to cause HCM and contractile dysfunction in vivo, we generated transgenic (TG) mice having cardiac-specific protein expression of cMyBP-CΔC10mut at approximately half the level of endogenous cMyBP-C. At 12 weeks of age, significant hypertrophy was observed in TG mice expressing cMyBP-CΔC10mut (heart weight/body weight ratio: 4.43 ± 0.11 mg/g non-transgenic (NTG) vs. 5.34 ± 0.25 mg/g cMyBP-CΔC10mut, P < 0.05). Furthermore, haematoxylin and eosin, Masson\'s trichrome staining, as well as second-harmonic generation imaging revealed the presence of significant fibrosis and a greater relative nuclear area in cMyBP-CΔC10mut hearts compared with NTG controls. M-mode echocardiography analysis revealed hypercontractile hearts (EF: 53.4%±2.9% NTG vs. 66.4% ± 4.7% cMyBP-CΔC10mut; P < 0.05) and early diastolic dysfunction (E/E\': 28.7 ± 3.7 NTG vs. 46.3 ± 8.4 cMyBP-CΔC10mut; P < 0.05), indicating the presence of an HCM phenotype. To assess whether these changes manifested at the myofilament level, contractile function of single skinned cardiomyocytes was measured. Preserved maximum force generation and increased Ca2+-sensitivity of force generation were observed in cardiomyocytes from cMyBP-CΔC10mut mice compared with NTG controls (EC50: 3.6 ± 0.02 µM NTG vs. 2.90 ± 0.01 µM cMyBP-CΔC10mut; P < 0.0001).
Conclusion
Expression of cMyBP-C protein with a modified C10 domain is sufficient to cause contractile dysfunction and HCM in vivo.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Cardiovasc Res: 30 Nov 2019; 115:1986-1997
Kuster DWD, Lynch TL, Barefield DY, Sivaguru M, ... Namakkal-Soorappan R, Sadayappan S
Cardiovasc Res: 30 Nov 2019; 115:1986-1997 | PMID: 31050699
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Abstract

Valve regurgitation in patients surviving endocarditis and the subsequent risk of heart failure.

Østergaard L, Dahl A, Bruun NE, Oestergaard LB, ... Ihlemann N, Fosbøl EL
Background
Significant valve regurgitation is common in patients surviving native valve infective endocarditis (IE), however the associated risk of heart failure (HF) subsequent to hospital discharge after IE is sparsely described.
Methods
We linked data from the East Danish Endocarditis Registry with administrative registries from 2002 to 2016 and included patients treated medically for IE who were discharged alive. Left-sided valve regurgitation was assessed by echocardiography at IE discharge and examined for longitudinal risk of HF. Multivariable adjusted Cox analysis was used to assess the associated risk of HF in patients with regurgitation (moderate or severe) compared with patients without regurgitation.
Results
We included 192 patients, 87 patients with regurgitation at discharge (30 with aortic regurgitation and 57 with mitral regurgitation) and 105 patients without. The cumulative risk of HF at 5 years of follow-up was 28.7% in patients with regurgitation at IE discharge and 12.4% in patients without regurgitation; the corresponding multivariable adjusted HR was 3.53 (95% CI 1.72 to 7.25). We identified an increased associated risk of HF for patients with aortic regurgitation (HR=2.91, 95% CI 1.14 to 7.43) and mitral regurgitation (HR=3.95, 95% CI 1.80 to 8.67) compared with patients without regurgitation. During follow-up, 21.9% and 5.7% underwent left-sided valve surgery among patients with and without regurgitation.
Conclusion
In patients surviving IE, treated medically, we observed that severe or moderate left-sided native valve regurgitation was associated with a significantly higher risk of HF compared with patients without regurgitation at IE discharge. Close monitoring of these patients is needed to initiate surgery timely.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 09 Dec 2019; epub ahead of print
Østergaard L, Dahl A, Bruun NE, Oestergaard LB, ... Ihlemann N, Fosbøl EL
Heart: 09 Dec 2019; epub ahead of print | PMID: 31822570
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Impact:
Abstract

Cardiovascular magnetic resonance: applications and practical considerations for the general cardiologist.

Arnold JR, McCann GP

Cardiovascular magnetic resonance (CMR) is a rapidly evolving non-invasive imaging modality offering comprehensive, multiparametric assessment of cardiac structure and function in a variety of clinical situations. Cine imaging with CMR is the gold standard non-invasive imaging technique for the quantification of ventricular volumes and systolic function. It also affords superior visualisation of apical and right ventricular morphological abnormalities. In coronary artery disease, CMR stress perfusion imaging identifies functionally significant coronary artery disease with high sensitivity and specificity, and international guidelines recommend CMR perfusion imaging in patients with chest pain at intermediate-high risk of coronary disease. Late gadolinium enhancement (LGE) imaging is the most sensitive imaging technique for identifying infarction/viability. In non-ischaemic cardiomyopathy, LGE imaging plays vital diagnostic and prognostic roles in a number of cardiomyopathies (eg, hypertrophic and dilated cardiomyopathies, and amyloidosis). In vivo tissue characterisation with CMR enables the identification of oedema/inflammation in acute coronary syndromes/myocarditis and the diagnosis of chronic fibrotic conditions (eg, in hypertrophic and dilated cardiomyopathy, aortic stenosis and amyloidosis). CMR T2* imaging uniquely offers non-invasive assessment of iron overload states, facilitating diagnosis and management. A multiparametric CMR approach also enables differentiation of cardiac masses/tumours and is a useful adjunct to echocardiography in the assessment of valve disease. The emergence of automated, inline, quantitative methodologies will expand the scope of CMR and reduce its cost in forthcoming years.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Dec 2019; epub ahead of print
Arnold JR, McCann GP
Heart: 10 Dec 2019; epub ahead of print | PMID: 31826937
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Abstract

A 63-year-old woman with multiple secondary tumours.

Muresan ID, Agoston-Coldea L, Dumitrascu DL

Clinical introductionA 63-year-old woman recently diagnosed with lung metastasis, after routine chest radiography, was admitted to our hospital for unspecified symptoms, such as dyspnoea on minimal exertion and dry cough. Physical examination showed uncommon signs. The electrocardiogram showed sinus rhythm and incomplete left bundle branch block. Thoracic CT scan revealed bilateral lung and pleural metastases and pelvic CT showed a right femoral bone mass. Transthoracic echocardiography revealed a heterogeneous mass, lateral to the right ventricle, with pericardial effusion. Further, cardiac MRI (cMRI) was performed (figure 1A,B). Diagnosis was completed with an ultrasound-guided biopsy and histopathological examination (figure 1C,D).heartjnl;106/3/202/F1F1F1Figure 1(A,B) Cardiac MRI: asterisk is suggestive of fluid and the white arrow indicates fibrous encapsulation by LGE, (C) H&E stain:white arrow indicating a tumoral cell with atypical mitosis and (D) immunohistochemical staining for smooth muscle actin antibody. QUESTION: Which of the following is the most likely diagnosis?Pericardial lymphoma.Pericardial leiomyosarcoma.Pericardial cyst.Secondary malignant cardiac tumour.Pericardial teratoma.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Jan 2020; 106:202-241
Muresan ID, Agoston-Coldea L, Dumitrascu DL
Heart: 30 Jan 2020; 106:202-241 | PMID: 31915242
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Abstract

Machine learning to predict the long-term risk of myocardial infarction and cardiac death based on clinical risk, coronary calcium, and epicardial adipose tissue: a prospective study.

Commandeur F, Slomka PJ, Goeller M, Chen X, ... Berman DS, Dey D
Aims
Our aim was to evaluate the performance of machine learning (ML), integrating clinical parameters with coronary artery calcium (CAC), and automated epicardial adipose tissue (EAT) quantification, for the prediction of long-term risk of myocardial infarction (MI) and cardiac death in asymptomatic subjects.
Methods and results
Our study included 1912 asymptomatic subjects [1117 (58.4%) male, age: 55.8 ± 9.1 years] from the prospective EISNER trial with long-term follow-up after CAC scoring. EAT volume and density were quantified using a fully automated deep learning method. ML extreme gradient boosting was trained using clinical co-variates, plasma lipid panel measurements, risk factors, CAC, aortic calcium, and automated EAT measures, and validated using repeated 10-fold cross validation. During mean follow-up of 14.5 ± 2 years, 76 events of MI and/or cardiac death occurred. ML obtained a significantly higher AUC than atherosclerotic cardiovascular disease (ASCVD) risk and CAC score for predicting events (ML: 0.82; ASCVD: 0.77; CAC: 0.77, P < 0.05 for all). Subjects with a higher ML score (by Youden\'s index) had high hazard of suffering events (HR: 10.38, P < 0.001); the relationships persisted in multivariable analysis including ASCVD-risk and CAC measures (HR: 2.94, P = 0.005). Age, ASCVD-risk, and CAC were prognostically important for both genders. Systolic blood pressure was more important than cholesterol in women, and the opposite in men.
Conclusions
In this prospective study, machine learning used to integrate clinical and quantitative imaging-based variables significantly improves prediction of MI and cardiac death compared with standard clinical risk assessment. Following further validation, such a personalized paradigm could potentially be used to improve cardiovascular risk assessment.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Cardiovasc Res: 18 Dec 2019; epub ahead of print
Commandeur F, Slomka PJ, Goeller M, Chen X, ... Berman DS, Dey D
Cardiovasc Res: 18 Dec 2019; epub ahead of print | PMID: 31853543
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Abstract

Diagnosis of coronary microvascular dysfunction in the clinic.

Ong P, Safdar B, Seitz A, Hubert A, Beltrame J, Prescott E

The coronary microcirculation plays a pivotal role in the regulation of coronary blood flow and cardiac metabolism. It can adapt to acute and chronic pathologic conditions such as coronary thrombosis or long-standing hypertension. Due to the fact that the coronary microcirculation cannot be visualized in human beings, in vivo its assessment remains challenging. Thus, the clinical importance of the coronary microcirculation is still often underestimated or even neglected. Depending on the clinical condition of the respective patient, several non-invasive (e.g. transthoracic Doppler-echocardiography assessing coronary flow velocity reserve, cardiac magnetic resonance imaging, positron emission tomography) and invasive methods (e.g. assessment of coronary flow reserve and microvascular resistance using adenosine, microvascular coronary spasm with acetylcholine) have been established for the assessment of coronary microvascular function. Individual patient characteristics, but certainly also local availability, methodical expertise and costs will influence which methods are being used for the diagnostic work-up (non-invasive and/or invasive assessment) in a patient with recurrent symptoms and suspected coronary microvascular dysfunction. Recently, the combined invasive assessment of coronary vasoconstrictor as well as vasodilator abnormalities has been titled interventional diagnostic procedure (IDP). It involves intracoronary acetylcholine testing for the detection of coronary spasm as well as coronary flow reserve and microvascular resistance assessment in response to adenosine using a dedicated wire. Currently, the IDP represents the most comprehensive coronary vasomotor assessment. Studies using the IDP to better characterize the endotypes observed will hopefully facilitate development of tailored and effective treatments.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: [email protected]

Cardiovasc Res: 05 Jan 2020; epub ahead of print
Ong P, Safdar B, Seitz A, Hubert A, Beltrame J, Prescott E
Cardiovasc Res: 05 Jan 2020; epub ahead of print | PMID: 31904824
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Abstract

Infective endocarditis complicating transcatheter aortic valve implantation.

Harding D, Cahill TJ, Redwood SR, Prendergast BD

Infective endocarditis complicating transcatheter aortic valve implantation (TAVI-IE) is a relatively rare condition with an incidence of 0.2%-3.1% at 1 year post implant. It is frequently caused by ,andWhile the incidence currently appears to be falling, the absolute number of cases is likely to rise substantially as TAVI expands into low risk populations following the publication of the PARTNER 3 and Evolut Low Risk trials. Important risk factors for the development of TAVI-IE include a younger age at implant and significant residual aortic regurgitation. The echocardiographic diagnosis of TAVI-IE can be challenging, and the role of supplementary imaging techniques including multislice computed tomography (MSCT) and positron emission tomography (FDG PET) is still emerging. Treatment largely parallels that of conventional prosthetic valve endocarditis (PVE), with prolonged intravenous antibiotic therapy and consideration of surgical intervention forming the cornerstones of management. The precise role and timing of cardiac surgery in TAVI-IE is yet to be defined, with a lack of clear evidence to help identify which patients should be offered surgical intervention. Minimising unnecessary healthcare interventions (both during and after TAVI) and utilising appropriate antibiotic prophylaxis may have a role in preventing TAVI-IE, but robust evidence for specific preventative strategies is lacking. Further research is required to better select patients for advanced hybrid imaging, to guide surgical management and to inform prevention in this challenging patient cohort.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 12 Jan 2020; epub ahead of print
Harding D, Cahill TJ, Redwood SR, Prendergast BD
Heart: 12 Jan 2020; epub ahead of print | PMID: 31932285
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Abstract

Cardiomyopathy associated with the Ala143Thr variant of the gene.

Valtola K, Nino-Quintero J, Hedman M, Lottonen-Raikaslehto L, ... Laakso M, Kuusisto J
Objective
To investigate whether the Ala143Thr variant of thegene (A143T/), with conflicting interpretations of pathogenicity, is associated with Fabry cardiomyopathy.
Methods
The index patient, a woman in her 60s with cardiomyopathy, was screened for variants in 59 cardiomyopathy-related genes. A143T/, the only rare variant found, was screened in 10 relatives. GLA activity and lyso-Gb3 levels were measured and echocardiography was performed in 8 of 9 subjects carrying A143T/. Cardiac magnetic resonance (CMR) imaging and F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) were performed in four adult A143T/ carriers. Endomyocardial biopsy was obtained from two adult A143T/ carrying sons of the index patient.
Results
The index patient and her elder son had a pacemaker implantation because of sick sinus syndrome and atrioventricular block. GLA activities were decreased to 25%-40% of normal in both sons and one granddaughter. Lyso-Gb3 levels were elevated in both sons. In CMR, the index patient and her two sons had left ventricular (LV) hypertrophy and/or dilatation. The elder son had late gadolinium enhancement, high CMR-derived T1 time and positive FDG signal in PET/CT in the basal inferolateral LV wall. The younger son had low T1 time and the mother had positive FDG signal in PET/CT in the basal inferolateral LV wall. Endomyocardial biopsy of both sons showed myocardial accumulation compatible with glycolipids in light and electron microscopy, staining with anti-Gb3 antibody available for the younger son. Five female relatives with A143T/ had no cardiomyopathy in cardiac imaging.
Conclusions
A143T/ is likely a late-onset Fabry cardiomyopathy causing variant with incomplete penetrance.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 15 Jan 2020; epub ahead of print
Valtola K, Nino-Quintero J, Hedman M, Lottonen-Raikaslehto L, ... Laakso M, Kuusisto J
Heart: 15 Jan 2020; epub ahead of print | PMID: 31949022
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Abstract

Advanced imaging for risk stratification of sudden death in hypertrophic cardiomyopathy.

Ramchand J, Fava AM, Chetrit M, Desai MY

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition, which typically manifests as left ventricular hypertrophy. A small subset of patients with HCM have an increased risk of sudden cardiac death (SCD) from ventricular arrhythmias. Risk of SCD can be effectively reduced following implantation of implantable cardiac defibrillators (ICD), although this treatment carries a risk of complications such as inappropriate shocks. With this in mind, we turn to advances in cardiac imaging to guide risk stratification for SCD and to select the appropriate individual who may benefit from ICD implantation. In this review, we have taken the opportunity to briefly summarise the role of imaging in the diagnosis of HCM before focusing on how specific imaging features influence risk of SCD in patients with HCM.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 15 Jan 2020; epub ahead of print
Ramchand J, Fava AM, Chetrit M, Desai MY
Heart: 15 Jan 2020; epub ahead of print | PMID: 31949025
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Abstract

Characteristics and Outcomes of Retinal Artery Occlusion: Nationally Representative Data.

Schorr EM, Rossi KC, Stein LK, Park BL, Tuhrim S, Dhamoon MS

Background and Purpose- There are few large studies examining comorbidities, outcomes, and acute interventions for patients with retinal artery occlusion (RAO). RAO shares pathophysiology with acute ischemic stroke (AIS); direct comparison may inform emergent treatment, evaluation, and secondary prevention. Methods- The National Readmissions Database contains data on ≈50% of US hospitalizations from 2013 to 2015. We used , , codes to identify and compare index RAO and AIS admissions, comorbidities, and interventions and Clinical Comorbidity Software codes to identify readmissions causes, using survey-weighted methods when possible. Cumulative risk of all-cause readmission after RAO ≤1 year was estimated by Kaplan-Meier analysis. Results- Among 4871 RAO and 1 239 963 AIS admissions, patients with RAO were less likely (<0.0001) than patients with AIS to have diabetes mellitus (RAO, 24.3% versus AIS, 36.8%), congestive heart failure (9.1% versus 14.8%), atrial fibrillation (15.5% versus 25.2%), or hypertension (62.2% versus 67.6%) but more likely to have valvular disease (13.3% versus 10.5%) and tobacco usage (38.6% versus 32.9%). In RAO admissions, thrombolysis was administered in 2.9% (5.8% in central RAO subgroup, versus 8.0% of AIS), therapeutic anterior chamber paracentesis in 1.0%, thrombectomy in none; 1.4% received carotid endarterectomy during index admission, 1.6% within 30 days. Nearly 1 in 10 patients with RAO were readmitted within 30 days and were more than twice as likely as patients with AIS to be readmitted for dysrhythmia or endocarditis. Readmission for stroke after RAO was the highest within the first 150 days after index admission, and risk was higher in central RAO than in branch RAO. Conclusions- Patients with RAO had high prevalence of many stroke risk factors, particularly valvular disease and smoking, which can be addressed to minimize subsequent risk. Despite less baseline atrial fibrillation, RAO patients were more likely to be readmitted for atrial fibrillation/dysrhythmias. A variety of interventions was administered. AIS risk is the highest shortly after RAO, emphasizing the importance of urgent, thorough neurovascular evaluation.



Stroke: 16 Jan 2020:STROKEAHA119027034; epub ahead of print
Schorr EM, Rossi KC, Stein LK, Park BL, Tuhrim S, Dhamoon MS
Stroke: 16 Jan 2020:STROKEAHA119027034; epub ahead of print | PMID: 31951154
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Abstract

Coagulation: at the heart of infective endocarditis.

Liesenborghs L, Meyers S, Vanassche T, Verhamme P

Infective endocarditis is a life-threatening and enigmatic disease with a mortality of 30% and a pathophysiology that is poorly understood. However, at its core, an endocarditis lesion is mainly a fibrin and platelet blood clot infested with bacteria, clinging at the cardiac valves. Infective endocarditis therefore serves as a paradigm of immunothrombosis gone wrong. Immunothrombosis refers to the entanglement of the coagulation system with innate immunity and the role of coagulation in the isolation and clearance of invading pathogens. However, in the case of infective endocarditis, instead of containing the infection, immunothrombosis inadvertently creates the optimal shelter from the immune system and allows some bacteria to grow almost unimpeded. In every step of the disease, the coagulation system is heavily involved. It mediates the initial adhesion of bacteria to the leaflets, fuels the growth and maturation of a vegetation and facilitates complications such as embolization and valve destruction. In addition, the number one cause of infective endocarditis Staphylococcus aureus has proven to be a true master manipulator of immunothrombosis and thrives in the fibrin rich environment of an endocarditis vegetation. Considering its central role in infective endocarditis, the coagulation system is an attractive therapeutic target for this deadly disease. There is however a very delicate balance at play and the use of antithrombotic drugs in patients with endocarditis is often accompanied with a high bleeding risk.

© 2020 International Society on Thrombosis and Haemostasis.

J Thromb Haemost: 09 Jan 2020; epub ahead of print
Liesenborghs L, Meyers S, Vanassche T, Verhamme P
J Thromb Haemost: 09 Jan 2020; epub ahead of print | PMID: 31925863
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Abstract

Sex Differences in Non-Obstructive Coronary Artery Disease.

Waheed N, Elias-Smale S, Malas W, Maas AH, ... Tremmel J, Mehta PK

Ischemic heart disease is a leading cause of morbidity and mortality in both women and men. Compared to men, symptomatic women who are suspected of having myocardial ischemia are more likely to have no obstructive coronary artery disease (CAD) on coronary angiography. Coronary vasomotor disorders and coronary microvascular dysfunction (CMD) have been increasingly recognized as important contributors to angina and adverse outcomes in patients with no obstructive CAD. CMD from functional and structural abnormalities in the microvasculature is associated with adverse cardiac events and mortality in both sexes. Women may be particularly susceptible to vasomotor disorders and CMD due to unique factors such as inflammation, mental stress, autonomic and neuro-endocrine dysfunction, which predispose to endothelial dysfunction and CMD. CMD can be detected with coronary reactivity testing and non-invasive imaging modalities; however, it remains underdiagnosed. This review focuses on sex differences in presentation, pathophysiologic risk factors, diagnostic testing, and prognosis of CMD.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: [email protected]

Cardiovasc Res: 19 Jan 2020; epub ahead of print
Waheed N, Elias-Smale S, Malas W, Maas AH, ... Tremmel J, Mehta PK
Cardiovasc Res: 19 Jan 2020; epub ahead of print | PMID: 31958135
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Abstract

Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy beyond ejection fraction.

Cannatà A, De Angelis G, Boscutti A, Normand C, ... Merlo M, Sinagra G

Sudden cardiac death and arrhythmia-related events in patients with non-ischaemic dilated cardiomyopathy (NICM) have been significantly reduced over the last couple of decades as a result of evidence-based pharmacological and non-pharmacological therapeutic strategies. Nevertheless, the arrhythmic stratification in patients with NICM remains extremely challenging, and the simple indication based on left ventricular ejection fraction appears to be insufficient. Therefore, clinicians need to go beyond the current criteria for implantable cardioverter-defibrillator implantation in the direction of a multiparametric evaluation of arrhythmic risk. Several parameters for arrhythmic risk stratification, ranging from electrocardiographic, echocardiographic, imaging-derived and genetic markers, are crucial for proper arrhythmic risk stratification and a multiparametric evaluation of risk in patients with NICM. In particular, integration of cardiac magnetic resonance parameters (mostly late gadolinium enhancement) and specific genetic information (ie, presence ofmutations) appears fundamental for proper implementation of the current arrhythmic risk stratification. Finally, a novel approach focused on both arrhythmic risk and prediction of left ventricular reverse remodelling during follow-up might be useful for effective multiparametric and dynamic arrhythmic risk stratification in NICM. In the future, a complete and integrated evaluation might be mandatory to implement arrhythmic risk prediction in patients with NICM and to discriminate the competing risk between heart failure-related events and life-threatening arrhythmias.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 20 Jan 2020; epub ahead of print
Cannatà A, De Angelis G, Boscutti A, Normand C, ... Merlo M, Sinagra G
Heart: 20 Jan 2020; epub ahead of print | PMID: 31964657
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Abstract

Brain Damage with Heart Failure: Cardiac Biomarker Alterations and Gray Matter Decline.

Mueller K, Thiel F, Beutner F, Teren A, ... Villringer A, Schroeter ML

Heart failure (HF) following heart damage leads to a decreased blood flow due to a reduced pump efficiency of the heart muscle. A consequence can be insufficient oxygen supply to the organism including the brain. While HF clearly shows neurological symptoms, such as fatigue, nausea and dizziness, the implications for brain structure are not well understood. Few studies show regional gray matter decrease related to HF, however, the underlying mechanisms leading to the observed brain changes remain unclear. To study the relationship between impaired heart function, hampered blood circulation and structural brain change in a case-control study.Within a group of 80 patients of the Leipzig Heart Center, we investigated a potential correlation between HF biomarkers and the brain\'s gray matter density (GMD) obtained by magnetic resonance imaging. We observed a significant positive correlation between cardiac ejection fraction and GMD across the whole frontal and parietal medial cortex reflecting the consequence of HF onto the brain\'s gray matter. Moreover, we also obtained a relationship between GMD and the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) - a biomarker that is used for screening, diagnosis and prognosis of HF. Here we found a significant negative correlation between NT-proBNP and GMD in the medial and posterior cingulate cortex but also in precuneus and hippocampus, which are key regions implicated in structural brain changes in dementia.We obtained significant correlations between brain structure and markers of heart failure including EF and NT-proBNP. A diminished GMD was found with decreased EF and increased NT-proBNP in wide brain regions including the whole frontomedian cortex as well as hippocampus and precuneus. Our observations might reflect structural brain damage in areas that are related to cognition, however, whether these structural changes facilitate the development of cognitive alterations has to be proven by further longitudinal studies.



Circ Res: 22 Jan 2020; epub ahead of print
Mueller K, Thiel F, Beutner F, Teren A, ... Villringer A, Schroeter ML
Circ Res: 22 Jan 2020; epub ahead of print | PMID: 31969053
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Abstract

Percutaneous occlusion of transseptal puncture-related free wall perforation at the coronary sinus with a ventricular septal occluder during left atrial appendage closure: A case report.

Bai Y, Zhang S, Qin YW, Zhao XX

Coronary sinus perforation is a life-threatening complication of transseptal puncture and needs to be repaired immediately. In this study, we report a case of a 74-year-old female patient with nonvalvular atrial fibrillation, who is a poor long-term anticoagulation candidate. During the manipulation of transseptal puncture, a perforation of the free right atrial wall at the coronary sinus ostium occurred, which was caused by the Brockenbrough needle and followed by the immediate advancement of an 8.5-French transseptal sheath. In consideration of the danger of cardiac tamponade after sheath removal, we decided to leave the 8.5-French sheath in the pericardial cavity. Then, we advanced a 6 mm ventricular septal occluder through the sheath. Finally, we achieved successful deployment of the device and closure of the perforation under the guidance of fluoroscopy and transthoracic echocardiography. Subsequently, the left atrial appendage orifice was occluded with a 21 mm Watchman device. This case illustrates that percutaneous device closure is feasible for inadvertent perforation of the free right atrial wall at the coronary sinus during transseptal puncture and should be considered as an alternative to surgery.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 05 Nov 2019; epub ahead of print
Bai Y, Zhang S, Qin YW, Zhao XX
Catheter Cardiovasc Interv: 05 Nov 2019; epub ahead of print | PMID: 31696654
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Abstract

Improvement in left ventricular function following higher-risk percutaneous coronary intervention in patients with ischemic cardiomyopathy.

Russo JJ, Prasad M, Doshi D, Karmpaliotis D, ... Moses JW, Kirtane AJ
Background
Surgical revascularization is associated with improved ventricular function and clinical outcomes among patients with ischemic cardiomyopathy. There are less extensive data on changes in ventricular function among patients with ischemic cardiomyopathy undergoing percutaneous coronary intervention (PCI). Accordingly, we sought to assess the extent and predictors of change in left ventricular ejection fraction (ΔLVEF) among patients undergoing hemodynamically-supported PCI.
Methods
We assessed ΔLVEF following hemodynamically-supported PCI (with Impella or intra-aortic balloon counterpulsation) among patients enrolled in the PROTECT II trial and cVAD registry. The ΔLVEF was compared among patients with paired echocardiography at baseline and at least 30 days of follow-up. Independent correlates of ΔLVEF (modeled continuously and with an absolute ΔLVEF≥5%) were assessed using multivariable models.
Results
Among the 689 patients with paired echocardiographic data included in the analysis, the mean LVEF improved from 24.8 ± 9.9% to 31.4 ± 13.3% after PCI, for a net increase of 6.5 ± 10.8% (p < .001). A total of 395 (57%) patients had ΔLVEF ≥ 5% following hemodynamically-supported PCI. The number of vessels treated was associated with ΔLVEF (ΔLVEF 5.5% with 1 vessel, 6.6% with 2 vessels, and 8.3% with 3 vessels, p for trend = .046). A lower baseline LVEF, absence of a history of congestive heart failure or aldosterone receptor antagonist use, and a greater number of vessels treated were independent correlates of LVEF improvement.
Conclusions
Among patients with severe left ventricular systolic dysfunction and paired echocardiographic assessments, an improvement in LVEF was observed following hemodynamically-supported PCI.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 05 Nov 2019; epub ahead of print
Russo JJ, Prasad M, Doshi D, Karmpaliotis D, ... Moses JW, Kirtane AJ
Catheter Cardiovasc Interv: 05 Nov 2019; epub ahead of print | PMID: 31693292
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Abstract

\"Between a rock and the mitral valve space\": Transcatheter mitral valve-in-valve implantation for paravalvular leak and refractory hemolysis complicated by circumflex coronary occlusion.

Adams HSL, Rajani R, Hildick-Smith D, Redwood S

Transcatheter mitral valve implantation (TMVI) is an emerging field in structural cardiology. A particularly difficult group to treat is high-risk patients requiring valve in mitral annular calcification (ViMAC) intervention, with overall poor procedural success and outcomes in recent registries. This case highlights an unusual complication of paravalvular regurgitation (PVL) through the uncovered stent frame of a balloon expandable transcatheter heart valve (THV) on the left ventricular side of the prosthesis, leading to mechanical hemolysis and subsequent anuric renal failure post a ViMAC procedure. Attempts to treat the PVL with an occlusion plug device were unsuccessful and led to left circumflex coronary occlusion secondary to mechanical compression of the vessel in the posterior mitral valve annulus, a previously unreported phenomenon. A repeat valve-in-valve procedure was performed to treat the PVL, and immediate angioplasty resolved the left circumflex occlusion. High-risk patients requiring TMVI pose multiple challenges to Heart Teams in the treatment of valve pathology. Optimal procedural planning, multimodality imaging, improved THVs, and the awareness of potential complications are fundamental in overcoming the learning curve of TMVI and improved outcome for patients requiring ViMAC.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 05 Nov 2019; epub ahead of print
Adams HSL, Rajani R, Hildick-Smith D, Redwood S
Catheter Cardiovasc Interv: 05 Nov 2019; epub ahead of print | PMID: 31696657
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Abstract

Identification of cardiac organ damage in arterial hypertension: insights by echocardiography for a comprehensive assessment.

Cameli M, Lembo M, Sciaccaluga C, Bandera F, ... Galderisi M,

: Arterial hypertension, a widespread disease, whose prevalence increases with age, represents a major risk factor for cardiovascular events, causing damage in several organs, including the heart. In this context, echocardiography has a clear and pivotal role, being able to assess cardiac morphology and detect haemodynamic changes induced by this disease. 2018 European Society of Cardiology/European Society of Hypertension guidelines on AH identified main echo parameters such as left ventricular mass, relative wall thickness and left atrial volume, for detecting cardiac organ damage. The present review highlights the advantage of additional echocardiographic parameters such as diastolic measurement and both thoracic and abdominal aortic dimensions. An overlook on aortic valve should also be suggested to detect aortic regurgitation and stenosis, both frequent complications in hypertensive patients. In this kind of comprehensive assessment, the combination of standard and advanced echocardiography (speckle tracking echocardiography and, with a lesser extent, three-dimensional echocardiography) could be considered to improve the diagnostic accuracy, stratify prognosis and address management in arterial hypertension.



J Hypertens: 03 Dec 2019; epub ahead of print
Cameli M, Lembo M, Sciaccaluga C, Bandera F, ... Galderisi M,
J Hypertens: 03 Dec 2019; epub ahead of print | PMID: 31809464
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Abstract

Perforation of a Stenotic Congenitally Bicuspid Aortic Valve Cusp by Heavy Calcium in the Other Cusp.

Roberts WC, Roberts CS, Kale I

On occasion in patients with stenotic congenitally bicuspid aortic valves (BAVs), the quantity of calcium in one of the cusps is considerably greater than in the other cusp. We examined operatively excised stenotic congenitally BAVs in 630 patients having isolated aortic valve replacement (No other cardiac valve was replaced, and none had had infective endocarditis.) Of the 630 valves, 3 contained a perforation in the mildly calcified cusp due to a large calcific \"spur\" extending across the orifice from a heavily calcified cusp. In conclusion, heavy calcific deposits in 1 of 2 BAVs may extend across the orifice causing a perforation in the noncalcified portion of the opposing cusp.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Jan 2020; 125:299-301
Roberts WC, Roberts CS, Kale I
Am J Cardiol: 14 Jan 2020; 125:299-301 | PMID: 31847960
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Abstract

Doppler-Derived Renal Venous Stasis Index in the Prognosis of Right Heart Failure.

Husain-Syed F, Birk HW, Ronco C, Schörmann T, ... Gall H, Ghofrani HA

Background Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods and Results We enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra-abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH-related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH-specific therapy escalation) and all-cause mortality for 1-year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (<0.0001) and was significantly associated with right heart and renal function, intra-abdominal pressure, and neurohormonal and hydration status. During follow-up, the morbidity/mortality end point occurred in 91 patients and was independently predicted by RVSI (RVSI in the third tertile versus referent: hazard ratio: 4.72 [95% CI, 2.10-10.59; <0.0001]). Receiver operating characteristic curves suggested superiority of RVSI to individual intrarenal venous flow patterns in predicting outcome (areas under the curve: 0.789 and 0.761, respectively; =0.038). Conclusions We propose RVSI as a conceptually new and integrative Doppler index of renal congestion. RVSI provides additional prognostic information to stratify PH for the propensity to develop right heart failure. Clinical Trial registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03039959.



J Am Heart Assoc: 04 Nov 2019; 8:e013584
Husain-Syed F, Birk HW, Ronco C, Schörmann T, ... Gall H, Ghofrani HA
J Am Heart Assoc: 04 Nov 2019; 8:e013584 | PMID: 31630601
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Abstract

Myocarditis Causing Premature Ventricular Contractions: Insights From the MAVERIC Registry.

Lakkireddy D, Turagam MK, Yarlagadda B, Dar T, ... Gopinathannair R, Natale A
Background
Premature ventricular contractions are a common clinical presentation that drives further diagnostic workup. We hypothesize the presence of underlying inflammation is often unrecognized in these patients with a potential for continued disease progression if not diagnosed and treated early in the disease course.
Methods
This is a single-center, prospective study including 107 patients with frequent symptomatic premature ventricular contractions (>5000/24 h) and no known ischemic heart disease. Patients underwent a combination of laboratory testing, 18F-fluorodeoxyglucose positron emission tomography scan, cardiac magnetic resonance imaging, and biopsy. Patients were diagnosed with myocarditis based on a multidisciplinary approach and treated with immunosuppressive therapy.
Results
The mean age of the cohort was 57±15 years, 41% were males, and left ventricular ejection fraction was 47±11.8%. Positive positron emission tomography scan was seen in 51% (55/107), of which 51% (28/55) had preserved left ventricle function. Based on clinical profile, 18F-fluorodeoxyglucose-positron emission tomography imaging, cardiac magnetic resonance, and histological data 58% patients (32/55) received immunosuppressive therapy alone and 25.4% (14/55) received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% (31/46) over a mean follow-up of 6±3 months. In patients with left ventricle systolic dysfunction, 37% (10/27) showed an improvement in mean left ventricular ejection fraction of 13±6%.
Conclusions
Approximately 51% of patients presenting with frequent premature ventricular contractions have underlying myocardial inflammation in this cohort. 18F-fluorodeoxyglucose-positron emission tomography scan can be a useful modality for early diagnosis and treatment with immunosuppressive therapy in selected patients can improve clinical outcomes.



Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007520
Lakkireddy D, Turagam MK, Yarlagadda B, Dar T, ... Gopinathannair R, Natale A
Circ Arrhythm Electrophysiol: 29 Nov 2019; 12:e007520 | PMID: 31838913
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Abstract

Temporal trends, outcomes, and predictors of mortality after pericardiocentesis in the United States.

Gad MM, Elgendy IY, Mahmoud AN, Elbadawi A, ... Kapadia SR, Jneid H
Background
Data regarding the temporal trends, outcomes, and predictors of in-hospital mortality after pericardiocentesis are limited.
Methods
The National Inpatient Sample database was used to extract hospitalizations of patients who underwent pericardiocentesis from January 2007 to September 2015. We examined the rates of in-hospital mortality, its predictors, and the temporal trends of pericardiocentesis utilization in the United States during the study period. We also examined trends and outcomes of pericardiocentesis associated with different cardiovascular procedures.
Results
A total of 96,377 hospitalizations with pericardiocentesis were examined. The number of pericardiocentesis procedures performed trended up significantly between 2007 and 2015 (p trend <.001), and this increase was observed predominantly in patients with unstable conditions. In-hospital mortality after pericardiocentesis decreased over time (14.6% in 2007 vs. 12.0% in 2015, p trend <.001), but remained higher than that after surgical pericardial intervention (13.1 vs. 8.9%, p value <.0001), predominantly attributable to a higher patient risk profile. Rates of in-hospital mortality were not statistically different between the procedural cohort and the nonprocedural cohort, 13.5 versus 13.0%, p value = .051. After multivariable adjustment, structural heart interventions (odds ratio [OR] 2.86; 95% confidence interval [CI] 2.35-3.49), bacterial and/or infective endocarditis (OR 2.09; 95% CI 1.72-2.54) and active neoplasms (OR 1.72; 95% CI 1.6-1.85) were independently associated with increased in-hospital mortality in pericardiocentesis patients.
Conclusion
In this nationwide analysis, the number of pericardiocentesis procedures increased significantly over time. Structural interventions, endocarditis, and active neoplasms were associated with increased in-hospital mortality after pericardiocentesis.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 07 Nov 2019; epub ahead of print
Gad MM, Elgendy IY, Mahmoud AN, Elbadawi A, ... Kapadia SR, Jneid H
Catheter Cardiovasc Interv: 07 Nov 2019; epub ahead of print | PMID: 31705624
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Abstract

Clinical correlates and subclinical cardiac organ damage in different extreme dipping patterns.

Cuspidi C, Facchetti R, Quarti-Trevano F, Dell\'Oro R, ... Grassi G, Mancia G
Aim
Information regarding the association of hypertension-mediated organ damage (HMOD) with extreme dipping pattern is scanty and not univocal. We sought to assess the clinical correlates of this blood pressure (BP) phenotype and its relationship with cardiac HMOD in the general population belonging to Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study.
Methods
The present analysis included all participants with good-quality ABPM recordings with reliable echocardiography at entry.
Results
A total of 792 out of 1597 patients (49.6%) exhibited an extreme dipping pattern (155 had a night-time reduction in both SBP and DBP at least 20% compared with daytime values and 637 a night-time reduction in DBP at least 20%); 34.2% were dippers and 16.2% nondippers. Left ventricular mass (LVM) indexed to height and LV hypertrophy (LVH) prevalence rates increased progressively from diastolic extreme dipping (14%), dipper (17%), systolic/diastolic extreme dipping (21%) to nondipper group (27%). However, after adjusting for confounders, statistical differences in both LVMI and LVH rates among the four groups disappeared. Similar results were obtained for LVM indexed to body surface area and absolute/indexed left atrial diameter.
Conclusion
Extreme dipping pattern is a BP phenotype highly frequent in the general population largely consisting of middle-aged individuals without prevalent cardiovascular disease. In this population, the extreme dipping pattern is not associated with an increased risk of cardiac HMOD, which suggests that the mechanisms invoked for the potential adverse cardiovascular effects of this condition (i.e. nocturnal hypoxemia, low-grade myocardial inflammation, coronary hypoperfusion, sympathetic activation at early morning, etc.) are not operative.



J Hypertens: 19 Jan 2020; epub ahead of print
Cuspidi C, Facchetti R, Quarti-Trevano F, Dell'Oro R, ... Grassi G, Mancia G
J Hypertens: 19 Jan 2020; epub ahead of print | PMID: 31977573
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Abstract

Rationale and design of the optical coherence tomography observation of pulmonary ultra-structural changes in heart failure (OCTOPUS-CHF) study.

Ortiz-Bautista C, Gutiérrez-Ibañes E, García-Cosío MD, Calviño-Santos R, ... Martínez-Solano J, Martínez-Sellés M
Background
The assessment of vascular remodeling using optical coherence tomography (OCT) has been previously described in some types of pulmonary hypertension. However, evidence about its feasibility and clinical utility for evaluation of pulmonary arterial vasculopathy in advanced heart failure (HF) is scarce. Optical Coherence Tomography Observation of Pulmonary Ultra-Structural Changes in Heart Failure (OCTOPUS-CHF) study is designed to study the correlation between OCT-morphometric parameters and hemodynamic data measured or derived from right heart catheterization (RHC).
Methods
OCTOPUS-CHF is an observational, prospective, multicentre study aiming to recruit 100 patients with advanced HF referred for heart transplantation (HTx) evaluation. As part of such evaluation, all patients will undergo RHC in order to rule out severe pulmonary hypertension. After RHC, a Dragonfly™ OPTIS™ imaging catheter will be used to perform OCT evaluation of a right-lower-lobe pulmonary artery with a luminal diameter ≤ 5 mm. The primary objective is to study the correlation of OCT parameters with hemodynamic RHC data. The secondary objective is to determine if OCT parameters improve prognostic stratification.
Conclusions
The OCTOPUS-CHF study will investigate the feasibility and clinical utility of pulmonary arterial vasculopathy evaluation with OCT in advanced HF patients and its correlation with hemodynamic RHC data. The ability of OCT-morphometric parameters to improve prognostic stratification will also be tested.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2020; 299:296-300
Ortiz-Bautista C, Gutiérrez-Ibañes E, García-Cosío MD, Calviño-Santos R, ... Martínez-Solano J, Martínez-Sellés M
Int J Cardiol: 14 Jan 2020; 299:296-300 | PMID: 31278027
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Abstract

Contraction alterations in Brugada syndrome; association with life-threatening ventricular arrhythmias.

Scheirlynck E, Van Malderen S, Motoc A, Lie ØH, ... Cosyns B, Droogmans S
Background
Brugada syndrome (BrS) is characterized by a high risk of sudden cardiac death. The clinical value of deformation imaging in patients with BrS is unknown. We aimed to assess whether echocardiographic speckle tracking parameters differ between: 1) BrS patients and healthy controls, 2) BrS patients with and without life-threatening ventricular arrhythmias.
Methods
Left ventricle (LV) and right ventricle (RV) longitudinal strain and mechanical dispersion (MD) were derived from echocardiography at inclusion. Clinical and ECG data were retrospectively assessed. A life-threatening ventricular arrhythmia was defined as an aborted cardiac arrest or sustained ventricular tachyarrhythmia.
Results
We included 175 BrS patients and 82 controls. LV and RV longitudinal strain were lower (-18.1 ± 2.6% vs. -18.8 ± 2.0%, p = 0.01 and - 24.4 ± 5.4% vs. 25.6 ± 3.7%, p = 0.04), while MD was higher [38 ± 11 ms vs. 33 ± 8 ms, p = 0.001 and 15 (8-25) ms vs. 11 (6-19) ms, p = 0.03] in BrS patients compared to controls. BrS patients who experienced a life-threatening ventricular arrhythmia (n = 19) had higher LV MD compared to those without events (43 ± 11 ms vs. 37 ± 11 ms, p = 0.02). An LV MD ≥40 ms was optimally associated with life-threatening ventricular arrhythmias [odds ratio 4.62 (95%CI 1.58-13.50), p = 0.005].
Conclusions
BrS patients had lower longitudinal strain and more heterogeneous contractions than healthy controls. Furthermore, BrS patients with a history of life-threatening ventricular arrhythmia had more heterogeneous LV contractions than those without. Therefore, LV MD may be a risk marker in BrS and its evaluation in prospective studies is needed.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2020; 299:147-152
Scheirlynck E, Van Malderen S, Motoc A, Lie ØH, ... Cosyns B, Droogmans S
Int J Cardiol: 14 Jan 2020; 299:147-152 | PMID: 31281045
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Abstract

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study.

Leerink JM, Feijen ELAM, van der Pal HJH, Kok WEM, ... Kremer LCM,
Background
Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure.
Objective
To describe the methodology of the Dutch LATER cardiology study (LATER CARD).
Methods
The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings.
Conclusions
The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 08 Nov 2019; 219:89-98
Leerink JM, Feijen ELAM, van der Pal HJH, Kok WEM, ... Kremer LCM,
Am Heart J: 08 Nov 2019; 219:89-98 | PMID: 31733449
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Abstract

Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi.

Carneiro ACA, Costa GP, Ferreira CS, Ramos IPR, ... Gonçalves RV, Talvani A
Background
Chagas heart disease is the most important clinical manifestation of Trypanosoma cruzi infection. Pharmacological therapies have been proposed aiming to reduce inflammatory response and cardiac damage in infected hosts. In this study, we investigated the use of doxycycline (Dox), in a sub-antimicrobial dose, in monotherapy and in combination with benznidazole (Bz) during the acute phase of infection with the VL-10 strain of T. cruzi, evaluating the therapeutic effect during the acute and chronic phases of the infection.
Methods and results
C57BL/6 mice were treated for 20 days with Dox (30 mg/kg), Bz (100 mg/kg), or both drugs in combination starting 9 days after infection. Parasitemia was measured during the acute phase and the animals were monitored for 12 months, after which echocardiography analysis was performed. Blood samples were obtained from euthanized mice for CCL2, CCL5, IL-10 analysis, and cardiac fragments were collected for histopathological evaluation. Dox treatment did not ameliorate parasitological/inflammatory parameters but reduced the cardiac collagen neoformation (CN) in 35%. In contrast, Bz administration reduced parasitemia, plasma levels of CCL2 and CCL5, and cardiac infiltration during acute infection, and reduced the level of IL-10 and CN (95%) at 12 months. Dox was unable to improve ejection fraction, while Bz treatment ameliorated the ejection fraction. No additive effect was observed in combination therapy.
Conclusion
Dox monotherapy is not effective in the acute or chronic phases of experimental cardiomyopathy induced by the VL-10 strain of T. cruzi. Furthermore, combination therapy with Dox does not potentiate the effects of Bz monotherapy.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2020; 299:243-248
Carneiro ACA, Costa GP, Ferreira CS, Ramos IPR, ... Gonçalves RV, Talvani A
Int J Cardiol: 14 Jan 2020; 299:243-248 | PMID: 31353153
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Abstract

Left bundle branch block-induced cardiomyopathy: a diagnostic proposal for a poorly explored pathological entity.

Sanna GD, Merlo M, Moccia E, Fabris E, ... Parodi G, Sinagra G

Despite being increasingly recognized as a specific disease, at the present time left bundle branch block (LBBB)-induced cardiomyopathy is neither formally included among unclassified cardiomyopathies nor among the acquired/non-genetic forms of dilated cardiomyopathy (DCM). Currently, a post-hoc diagnosis of LBBB-induced cardiomyopathy is possible when evaluating patients\' response to cardiac resynchronization therapy (CRT). However, an early detection of a LBBB-induced cardiomyopathy could have significant clinical and therapeutic implications. Patients with the aforementioned form of dyssynchronopathy may benefit from early CRT and overall prognosis might be better as compared to patients with a primary muscle cell disorder (i.e. \"true\" DCM). The real underlying mechanisms, the possible genetic background as well as the early identification of this specific form of DCM remain largely unknown. In this review the complex relationship between LBBB and left ventricular non-ischaemic dysfunction is described. Furthermore, a multiparametric approach based on clinical, electrocardiographic and imaging red flags, is provided in order to allow an early detection of the LBBB-induced cardiomyopathy.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2020; 299:199-205
Sanna GD, Merlo M, Moccia E, Fabris E, ... Parodi G, Sinagra G
Int J Cardiol: 14 Jan 2020; 299:199-205 | PMID: 31186131
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Abstract

Biventricular pacing during cardiac magnetic resonance imaging.

Vago H, Czimbalmos C, Papp R, Szabo L, ... Geller L, Merkely B
Aims
We aimed to assess the effect of cardiac resynchronization on left ventricular (LV) function, volumes, geometry, and mechanics in order to demonstrate reverse remodelling using cardiac magnetic resonance (CMR) with resynchronization on.
Methods and results
New York Heart Association (NYHA) Class II-III patients on optimal medical therapy with LV ejection fraction (LVEF) ≤35%, and complete LBBB with broad QRS (>150 ms) were prospectively recruited. Cardiac magnetic resonance examination was performed at baseline and at 6-month follow-up, applying both biventricular and AOO pacing. The following data were measured: conventional CMR parameters, remodelling indices, global longitudinal, circumferential, radial strain, global dyssynchrony [mechanical dispersion (MD) defined as the standard deviation of time to peak longitudinal/circumferential strain in 16 LV segments], and regional dyssynchrony (maximum differences in time between peak septal and lateral transversal displacement). Thirteen patients (64 ± 7 years, 38% male) were enrolled. Comparing the baseline and follow-up CMR parameters measured during biventricular pacing, significant increase in LVEF, and decrease in LV end-diastolic volume index (LVEDVi) and LV end-systolic volume index (LVESVi) were found. Left ventricular remodelling indices, global longitudinal, circumferential, and radial strain values showed significant improvement. Circumferential MD decreased (20.5 ± 5.5 vs. 13.4 ± 3.4, P < 0.001), while longitudinal MD did not change. Regional dyssynchrony drastically improved (362 ± 96 vs. 104 ± 66 ms, P < 0.001). Applying AOO pacing resulted in an immediate deterioration in LVEF, LVESVi, circumferential strain, global and regional dyssynchrony.
Conclusion
Cardiac magnetic resonance imaging during biventricular pacing is feasible and enables a more precise quantification of LV function, morphology, and mechanics. As a result, it may contribute to a better understanding of the effects of resynchronization therapy and might improve responder rate in the future.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Europace: 11 Nov 2019; epub ahead of print
Vago H, Czimbalmos C, Papp R, Szabo L, ... Geller L, Merkely B
Europace: 11 Nov 2019; epub ahead of print | PMID: 31713632
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Abstract

Antibiotic prophylaxis of infective endocarditis in patients with predisposing cardiac conditions: French cardiologists\' implementation of current guidelines.

Cloitre A, Lesclous P, Trochu Q, Selton-Suty C, ... Duval X, Trochu JN
Background
To prevent infective endocarditis (IE), with the exception of the United Kingdom, antibiotic prophylaxis (AP) is recommended in patients with predisposing cardiac conditions (PCCs) worldwide. To conclude on the relevance of this strategy, how the current guidelines are applied is a crucial point to investigate. The first aim of this study was to assess cardiologists\' implementation of the current guidelines. The secondary objective was to identify specific areas where the training and knowledge of French cardiologists could be improved.
Methods
A national online survey was carried out among the 2228 cardiologist members of the French Society of Cardiology.
Results
The high risk PCCs for which IE AP is recommended were correctly identified by the vast majority of the respondents so that IE AP is mostly prescribed correctly in such patients. But only 12% identified all the right indications for IE AP according to 13 predefined PCCs (3 at high-risk, 6 at moderate-risk and 4 at low-risk of IE) so that some IE AP misuses are recorded, overprescription in particular. Only 47% prescribed the proper amoxicillin schedule and only 15% prescribed the appropriate clindamycin schedule in cases with penicillin allergy.
Conclusion
This study evidenced relevant areas where the training of cardiologists could be improved such as knowledge of the risk of IE for certain PCCs and some common invasive dental procedures. Cardiologists\' knowledge should be improved before any conclusion can be drawn on the relevance of this AP strategy and its influence on IE incidence.

Copyright © 2019. Published by Elsevier B.V.

Int J Cardiol: 14 Jan 2020; 299:222-227
Cloitre A, Lesclous P, Trochu Q, Selton-Suty C, ... Duval X, Trochu JN
Int J Cardiol: 14 Jan 2020; 299:222-227 | PMID: 31327512
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Abstract

Atrioventricular mechanical coupling and major adverse cardiac events in female patients following acute ST elevation myocardial infarction.

Backhaus SJ, Kowallick JT, Stiermaier T, Lange T, ... Eitel I, Schuster A
Background
Sex-specific outcome data following myocardial infarction (MI) are inconclusive with some evidence suggesting association of female sex and increased major adverse cardiac events (MACE). Since mechanistic principles remain elusive, we aimed to quantify the underlying phenotype using cardiovascular magnetic resonance (CMR) quantitative deformation imaging and tissue characterisation.
Methods
In total, 795 ST-elevation MI patients underwent post-interventional CMR imaging. Feature-tracking (CMR-FT) was performed in a blinded core-laboratory. Left ventricular function was quantified using ejection fraction (LVEF) and global longitudinal/circumferential/radial strains (GLS/GCS/GRS). Left atrial function was assessed by reservoir (εs), conduit (εe) and booster-pump strains (εa). Tissue characterisation included infarct size, microvascular obstruction and area at risk. Primary endpoint was the occurrence of MACE within 1 year.
Results
Female sex was associated with increased MACE (HR 1.96, 95% CI 1.13-3.42, p = 0.017) but not independently of baseline confounders (p = 0.526) with women being older, more often diabetic and hypertensive (p < 0.001) and of higher Killip-class (p = 0.010). Tissue characterisation was similar between sexes. Women showed impaired atrial (εs p = 0.011, εe p < 0.001) but increased systolic ventricular mechanics (GLS p = 0.001, LVEF p = 0.048). While atrial and ventricular function predicted MACE in men only LV GLS and GCS were associated with MACE in women irrespective of confounders (GLS p = 0.036, GCS p = 0.04).
Conclusion
In men ventricular systolic contractility is impaired and volume assessments precisely stratify elevated risks. In contrast, women experience reduced atrial but increased ventricular systolic strain. This may reflect ventricular diastolic failure with systolic compensation, which is independently associated with MACE adding incremental value to sex-specific prognosis evaluation.

Copyright © 2019 Elsevier B.V. All rights reserved.

Int J Cardiol: 14 Jan 2020; 299:31-36
Backhaus SJ, Kowallick JT, Stiermaier T, Lange T, ... Eitel I, Schuster A
Int J Cardiol: 14 Jan 2020; 299:31-36 | PMID: 31300172
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Abstract

Tissue-specific analysis of lipid species in during overnutrition by UHPLC-MS/MS and MALDI-MSI.

Tuthill BF, Searcy LA, Yost RA, Musselman LP

Diets high in calories can be used to model metabolic diseases including obesity and its associated comorbidities, in animals.  Drosophila melanogaster fed high-sugar diets exhibit complications of human obesity including hyperglycemia, hyperlipidemia, insulin resistance, cardiomyopathy, increased susceptibility to infection, and reduced longevity. We hypothesize that lipid storage in the high sugar-fed fly\'s fat body reaches a maximum capacity, resulting in the accumulation of toxic lipids in other tissues, or lipotoxicity.  We took two approaches to characterize tissue-specific lipotoxicity. Ultra-high-performance liquid chromatography- tandem mass spectrometry (UHPLC-MS/MS) and matrix-assisted laser desorption/ionization - mass spectrometry imaging (MALDI-MSI) enabled spatial and temporal localization of lipid species in the fat body, heart, and hemolymph. Substituent chain length was diet-dependent, with fewer odd-chain esterified fatty acids on high sugar diets in all sample types. By contrast, dietary effects on double-bond content differed among organs, consistent with a model where some substituent pools are shared, and others are spatially restricted. Both di- and tri-glycerides increased on high sugar diets in all sample types, similar to observations in obese humans. Interestingly, there were dramatic effects of sugar feeding on lipid ethers, which have not been previously associated with lipotoxicity. Taken together, we have identified candidate endocrine mechanisms and molecular targets that may be involved in metabolic disease and lipotoxicity.

Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

J Lipid Res: 02 Jan 2020; epub ahead of print
Tuthill BF, Searcy LA, Yost RA, Musselman LP
J Lipid Res: 02 Jan 2020; epub ahead of print | PMID: 31900315
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Impact:
Abstract

Initial experiences with a novel biodegradable device for percutaneous closure of atrial septal defects: From preclinical study to first-in-human experience.

Li YF, Xie YM, Chen J, Li BN, ... Wang SS, Zhang ZW
Objective
To evaluate the feasibility, safety, and effectiveness of a novel, absorbable atrial septal defect (ASD) closure device made of poly-l-lactic acid (PLLA) in a swine model of ASD and for the first time in humans.
Methods
A preclinical safety study was conducted using a swine model of ASD. In a clinical setting, five pediatric patients underwent ASD closure with the PLLA device with fluoroscopic and transthoracic echocardiography guidance. The procedural results and clinical outcomes at 1 day, 30 days, 3 months, and 6 months after closure were analyzed.
Results
The 24- and 36-month follow-up results of the preclinical study demonstrated that the PLLA device exhibited good endothelialization and degradability in the swine model. In the clinical study, successful device implantation was achieved in all five patients (median age, 3.6 years; range, 3.1-6.5 years). The mean defect size was (13.6 ± 2.7) mm. Follow-up at 30 days, 3 months, and 6 months was completed in all five cases. The complete defect closure rates with no residual shunt at 30 days, 3 months, and 6 months follow-up were 60% (3/5), 80% (4/5), and 80% (4/5), respectively. No device dislodgement, significant aortic valve or mitral valve regurgitation, new onset cardiac arrhythmia, or other adverse events were reported.
Conclusion
The study results demonstrated that it is feasible to implant the PLLA device for closure of small to medium sized ASDs without significant residual shunts or severe adverse events in humans. The PLLA device exhibited good endothelialization and degradability in the swine model at 24 and 36 months. Further studies to evaluate long-term safety and effectiveness with the device in a large cohort of patients are warranted.

© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 11 Nov 2019; epub ahead of print
Li YF, Xie YM, Chen J, Li BN, ... Wang SS, Zhang ZW
Catheter Cardiovasc Interv: 11 Nov 2019; epub ahead of print | PMID: 31714687
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Impact:
Abstract

Hemodynamic Validation of the E/e\' Ratio as a Measure of Left Ventricular Filling Pressure in Patients With Non-ST Elevation Myocardial Infarction.

Prasad SB, Camuglia A, Lo A, Holland DJ, ... Thomas L, Atherton JJ

The E/e\' ratio has an established role in the assessment of left ventricular filling pressure (LVFP) in stable patients, but its accuracy in acute myocardial ischemia is less well established. The aim of this study was to validate the relation between the E/e\' ratio and invasively measured LVFP in patients with non-ST elevation myocardial infarction (NSTEMI). A total of 120 unselected patients with NSTEMI underwent cardiac catheterization with measurement of left ventricular end-diastolic pressure (LVEDP; elevated ≥15 mm Hg) and Doppler echocardiography with either simultaneous (n = 30) or same-day (n = 90) measurement of E/e\'. Patients were aged 64.1 ± 11.8 years, 72% were male and mean left ventricular ejection fraction was 48.0 ± 20.9%. Septal, lateral, and average E/e\' ratios all showed a significant correlation with LVEDP (Pearson\'s r: 0.42, 0.43, 0.48, respectively [all p <0.001]). Receiver operating characteristics curves showed an area under the curve of 0.72, 0.72, and 0.75 (all p <0.001) for septal, lateral, and average E/e\', respectively. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values for the guideline-recommended threshold of average E/e\' >14 for elevated LVEDP was 27%, 93%, 79%, and 44%, respectively. Utilizing lower E/e\' boundaries of 6, 7, and 8 for lateral, average, and medial E/e\', respectively, improved the NPV to ≥80% for each parameter. In conclusion, the E/e\' ratio is a robust measure of LVFP during acute NSTEMI using upper and lower thresholds to achieve a high PPV and NPV, respectively, with the use of adjunctive guideline-recommend measures required in patients with nonconclusive E/e\'.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

Am J Cardiol: 18 Nov 2019; epub ahead of print
Prasad SB, Camuglia A, Lo A, Holland DJ, ... Thomas L, Atherton JJ
Am J Cardiol: 18 Nov 2019; epub ahead of print | PMID: 31836128
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Abstract

Design, methodology and baseline characteristics of the Women\'s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD).

Quesada O, AlBadri A, Wei J, Shufelt C, ... Pepine CJ, Merz CNB

A significant number of women with signs and symptoms of ischemia with no obstructive coronary artery disease (INOCA) have coronary vascular dysfunction detected by invasive coronary reactivity testing (CRT). However, the noninvasive assessment of coronary vascular dysfunction has been limited.
Methods
The Women\'s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) was a prospective study of women with suspected INOCA aimed to investigate whether (1) cardiac magnetic resonance imaging (CMRI) abnormalities in left ventricular morphology and function and myocardial perfusion predict CRT measured coronary microvascular dysfunction, (2) these persistent CMRI abnormalities at 1-year follow-up predict persistent symptoms of ischemia, and (3) these CMRI abnormalities predict cardiovascular outcomes. By design, a sample size of 375 women undergoing clinically indicated invasive coronary angiography for suspected INOCA was projected to complete baseline CMRI, a priori subgroup of 200 clinically indicated CRTs, and a priori subgroup of 200 repeat 1-year follow-up CMRIs.
Results
A total of 437 women enrolled between 2008 and 2015, 374 completed baseline CMRI, 279 completed CRT, and 214 completed 1-year follow-up CMRI. Mean age was 55± 11 years, 93% had 20%-50% coronary stenosis, and 7% had <20% stenosis by angiography.
Conclusions
The WISE-CVD study investigates the utility of noninvasive CMRI to predict coronary vascular dysfunction in comparison to invasive CRT, and the prognostic value of CMRI abnormalities for persistent symptoms of ischemia and cardiovascular outcomes in women with INOCA. WISE-CVD will provide new understanding of a noninvasive imaging modality for future clinical trials.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am Heart J: 04 Dec 2019; 220:224-236
Quesada O, AlBadri A, Wei J, Shufelt C, ... Pepine CJ, Merz CNB
Am Heart J: 04 Dec 2019; 220:224-236 | PMID: 31884245
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Abstract

Transesophageal echocardiography complications associated with interventional cardiology procedures.

Freitas-Ferraz AB, Rodés-Cabau J, Junquera Vega L, Beaudoin J, ... O\'Hara G, Bernier M
Background
Although there have been several reports documenting complications related with transesophageal echocardiography (TEE) manipulation following cardiac surgery, there is a paucity of data regarding the safety of TEE used to guide catheter-based interventions. The aim of this study was to determine the prevalence, types and risk factors of complications associated with procedures requiring active TEE guidance.
Methods
This study included 1249 consecutive patients undergoing either transcatheter aortic valve implantation (TAVI), Mitraclip, left atrial appendage occlusion (LAAO) or paravalvular leak closure (PVLC). Patients were divided into 2 cohorts based on the degree of probe manipulation required to guide the procedure and the risk of developing a TEE-related complication: low-risk (TAVI, n = 1037) and high-risk (Mitraclip, LAAO and PVLC, n = 212). Patients were further analyzed according to the occurrence of major and minor TEE-related complications.
Results
The overall incidence of TEE-related complications was 0.9% in the TAVI group and 6.1% in the rest of the cohort (P < .001). Patients in the high-risk cohort had also a higher incidence of major-complications (2.8% vs 0.6%, P = .008), and factors associated with an increased risk were being underweight, having a prior history of gastrointestinal bleeding and the use of chronic steroids/immunosuppressive medications. Procedural time under TEE-manipulation was longer in patients exhibiting complications and was an independent predictor of major complications (OR = 1.13, 95% CI 1.01-1.25, for each 10 minutes increments in imaging time). Patients with major complications undergoing Mitraclip had the longest median time under TEE-manipulation (297 minutes) and a risk of developing a major-complication that was 10.64 times higher than the rest of the cohort (95% CI 3.30-34.29, P < .001).
Conclusion
The prevalence of TEE-related complications associated with interventional procedures is higher than previously reported. Undergoing a prolonged procedure, particularly in the setting of Mitraclip, was the main factor linked to TEE-related complications.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am Heart J: 08 Dec 2019; 221:19-28
Freitas-Ferraz AB, Rodés-Cabau J, Junquera Vega L, Beaudoin J, ... O'Hara G, Bernier M
Am Heart J: 08 Dec 2019; 221:19-28 | PMID: 31896037
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Abstract

Myocardial dysfunction in long-term breast cancer survivors treated at ages 40-50 years.

Jacobse JN, Steggink LC, Sonke GS, Schaapveld M, ... Gietema JA, van Leeuwen FE
Aims
Anthracyclines increase heart failure (HF) risk, but the long-term prevalence of myocardial dysfunction in young breast cancer (BC) survivors is unknown. Early measures of left ventricular myocardial dysfunction are needed to identify BC patients at risk of symptomatic HF.
Methods and results
Within an established cohort, we studied markers for myocardial dysfunction among 569 women, who were 5-7 years (n = 277) or 10-12 years (n = 292) after BC treatment at ages 40-50 years. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured in serum. Associations between patient-related and treatment-related risk factors and myocardial dysfunction were evaluated using linear and logistic regression. Median ages at BC diagnosis and cardiac assessment were 46.7 and 55.5 years, respectively. Anthracycline-treated patients (n = 313), compared to the no-anthracycline group (n = 256), more often had decreased LVEF (10% vs. 4%), impaired GLS (34% vs. 27%) and elevated NT-proBNP (23% vs. 8%). GLS and LVEF declined in a linear fashion with increasing cumulative anthracycline dose (GLS: +0.23 and LVEF: -0.40 per cycle of 60 mg/m ; P < 0.001) and GLS was worse for patients with left breast irradiation. The risk of NT-proBNP >125 ng/L was highest for patients who received 241-300 mg/m anthracycline dose compared to the no-anthracycline group (odds ratio: 3.30, 95% confidence interval: 1.83-5.96).
Conclusion
Impaired GLS and increased NT-proBNP levels are present in a substantial proportion of young BC survivors treated with anthracyclines. Whether this will lead to future cardiac disease needs to be evaluated by longitudinal assessment.

© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 05 Nov 2019; epub ahead of print
Jacobse JN, Steggink LC, Sonke GS, Schaapveld M, ... Gietema JA, van Leeuwen FE
Eur J Heart Fail: 05 Nov 2019; epub ahead of print | PMID: 31696625
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Abstract

Determinants of Cardiorespiratory Fitness Following Thoracic Radiotherapy in Lung or Breast Cancer Survivors.

Canada JM, Trankle CR, Carbone S, Buckley LF, ... Weiss E, Abbate A

We measured peak oxygen consumption (VO) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as measured by reduced peak VO, a marker of impaired cardiovascular reserve. We enrolled 25 subjects 1.8 (0.1 to 8.2) years following completion of thoracic radiotherapy with significant heart exposure (at least 10% of heart volume receiving at least 5 Gray). All subjects underwent cardiopulmonary exercise testing, Doppler echocardiography, and circulating biomarkers assessment. The cohort included 16 Caucasians (64%), 15 women (60%) with a median age of 63 (59 to 66) years. The peak VO was 16.8 (13.5 to 21.9) ml·kg·min or moderately reduced at 62% (50% to 93%) of predicted. The mean cardiac radiation dose was 5.4 (3.7 to 14.7) Gray, and it significantly correlated inversely with peak VO (R = -0.445, p = 0.02). Multivariate regression analysis revealed the diastolic functional reserve index and the N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels were independent predictors of peak VO (ß = +0.813, p <0.01 and ß = -0.414, p = 0.04, respectively). In conclusion, patients who had received thoracic radiation display a dose-dependent relation between the cardiac radiation dose received and the impairment in peak VO, the reduction in diastolic functional reserve index, and elevation of NTproBNP.

Copyright © 2019 Elsevier Inc. All rights reserved.

Am J Cardiol: 25 Dec 2019; epub ahead of print
Canada JM, Trankle CR, Carbone S, Buckley LF, ... Weiss E, Abbate A
Am J Cardiol: 25 Dec 2019; epub ahead of print | PMID: 31928717
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Abstract

Identifying Risk Factors for Massive Right Ventricular Dilation in Patients With Repaired Tetralogy of Fallot.

Cochran CD, Yu S, Gakenheimer-Smith L, Lowery R, ... Agarwal PP, Dorfman AL

In repaired tetralogy of Fallot (rTOF), pulmonary insufficiency results in varying degrees of right ventricle (RV) dilation. A subset of patients is diagnosed at initial cardiac magnetic resonance imaging (CMR) with a massively dilated RV, far beyond pulmonary valve replacement (PVR) criteria, which is unlikely to return to normal size after PVR. This study aimed to identify risk factors for massive RV dilation at initial CMR. This nested case-control study included all patients at our institution with rTOF and massive RV dilation (indexed RV end-diastolic volume [RVEDVi] ≥200 ml/m) on initial CMR. Patients were matched by age at first CMR, gender, and type of repair with rTOF controls with RVEDVi<200 ml/m. In 39 cases (median RVEDVi 227 ml/m, interquartile range [IQR] 213 to 250) and 73 controls (median RVEDVi 155 ml/m, IQR 130 to 169), repair at >6 months of age, longer QRS duration, and non-Caucasian race were significantly associated with massive RV dilation on univariate analysis. In multivariate analysis, repair at >6 months of age (adjusted odds ratio [AOR] 2.90, 95% confidence interval [CI] 1.12 to 7.55, p = 0.03), longer QRS duration (AOR = 1.03, 95% CI 1.01 to 1.05, p = 0.005), and non-Caucasian race (AOR = 7.84, 95% CI 1.76 to 34.8, p = 0.01) remained independently associated with massive RV dilation. Era of repair, history of systemic to pulmonary shunt palliation, genetic anomaly, and additional cardiac lesions did not differ between groups. In conclusion, these risk factors identify a subset of patients who may benefit from earlier CMR evaluation to avoid massive irreversible RV dilation.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 27 Dec 2019; epub ahead of print
Cochran CD, Yu S, Gakenheimer-Smith L, Lowery R, ... Agarwal PP, Dorfman AL
Am J Cardiol: 27 Dec 2019; epub ahead of print | PMID: 31964501
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Abstract

Effect of Pressure Recovery on Pressure Gradients in Congenital Stenotic Outflow Lesions in Pediatric Patients-Clinical Implications of Lesion Severity and Geometry: A Simultaneous Doppler Echocardiography and Cardiac Catheter Correlative Study.

Singh GK, Mowers KL, Marino C, Balzer D, Rao PS
Background
Doppler pressure gradients (PGs) are routinely used as a surrogate for catheter peak-to-peak gradient (PPG) for referring pediatric patients with aortic stenosis (AS), pulmonary stenosis (PS), and coarctation of the aorta (CoA) for intervention but do not always predict the catheter PPG accurately, which results in misclassification of lesion severity. We hypothesized that recovered pressure (RP) accounts for the discrepancy between Doppler PG and catheter PPG. We aimed to study the occurrence of clinically significant RP in AS, PS, and CoA.
Methods
Simultaneous Doppler and catheter PGs were prospectively measured in 82 patients (median age, 12.2 months; weight, 7.5 kg) with isolated AS (n = 30), PS (n = 24), and CoA (n = 28), and agreement before and after correcting for RP were analyzed. RP was calculated from a fluid dynamic-based equation. Effects of lesion geometry on the magnitude of RP were analyzed.
Results
Recovered pressure-corrected Doppler peak instantaneous gradient (PIG) had significantly closer agreement and correlation with the catheter PPG (P < .001) than the uncorrected PIG and mean Doppler gradients. Recovered pressure-corrected Doppler PIG predicted PPG with high specificity and accuracy in all lesions (95% CI, 36%-97% and 85%-100%, respectively, P < .05 for both). RP magnitude was weakly related (r = 0.33 to 0.47) to valve area and inversely related (r = -0.22 to -0.34) to downstream vessel area.
Conclusions
Significant RP occurs in congenital AS, PS, and CoA, accounting for misclassification of lesion severity by Doppler PIG. The RP magnitude is at a maximum in mild to moderate stenotic outflow lesions, with small-size downstream vessels causing the most misclassification of lesion severity by Doppler PIG.

Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 03 Nov 2019; epub ahead of print
Singh GK, Mowers KL, Marino C, Balzer D, Rao PS
J Am Soc Echocardiogr: 03 Nov 2019; epub ahead of print | PMID: 31699474
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Abstract

Early improvement of left ventricular ejection fraction by cardiac resynchronization through His bundle pacing in patients with heart failure.

Moriña-Vázquez P, Moraleda-Salas MT, Manovel-Sánchez AJ, Fernández-Gómez JM, ... Venegas-Gamero J, Barba-Pichardo R
Aims
Permanent His bundle pacing (p-HBP) can correct intraventricular conduction disorders and could be an alternative to traditional cardiac resynchronization therapy (CRT) via the coronary sinus. We describe the short-term impact of HBP on left ventricular ejection fraction (LVEF) and improvement of left intraventricular synchrony.
Methods and results
This prospective descriptive study, performed from January 2018 to February 2019, included patients with left bundle branch block (LBBB) and an CRT indication who were resynchronized by p-HBP. We used the Medtronic C315 His catheter or a combination of the CPS-Direct-Universal introducer, CPS-AIM™-Universal subselector (Abbot), and SelectSecure™ MRI-SureScan™ 3830 lead. Correction of the LBBB by HBP had been previously checked. At 1 month of follow-up, we analysed the quantification of LVEF and measurement of the delay of the septal wall with the posterior wall as a parameter of intraventricular synchrony. We included 48 patients with LBBB and an indication for CRT. With HBP, we corrected the LBBB in 81% of patients (n = 39), and we achieved cardiac resynchronization through permanent HBP in 92% of these patients (n = 36). Left ventricular ejection fraction and intraventricular mechanical resynchronization improved in all patients, which was demonstrated by echocardiography through the improvement of the delay of the septal wall with the posterior wall from 138 ms (range 131-151) to 41 ms (19-63).
Conclusion
There is early improvement after p-HBP in LVEF and left ventricular electromechanical synchronization in patients with LBBB, heart failure, and an indication for CRT.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 19 Nov 2019; epub ahead of print
Moriña-Vázquez P, Moraleda-Salas MT, Manovel-Sánchez AJ, Fernández-Gómez JM, ... Venegas-Gamero J, Barba-Pichardo R
Europace: 19 Nov 2019; epub ahead of print | PMID: 31746996
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Abstract

Functional Regurgitation of Atrioventricular Valves and Atrial Fibrillation: An Elusive Pathophysiological Link Deserving Further Attention.

Muraru D, Guta AC, Ochoa-Jimenez RC, Bartos D, ... Basso C, Badano LP

In patients with structurally normal atrioventricular valvular apparatus, functional regurgitation of the mitral or tricuspid valves has been attributed mainly to ventricular dilation and/or dysfunction, through a combination of annulus dilation and tethering of the valve leaflets. The occurrence of functional regurgitation of atrioventricular valves in patients with long-standing persistent atrial fibrillation and atrial dilation but normal ventricular size and function has received much less attention, and its peculiar mechanisms still remain to be understood. This distinct form of functional regurgitation (i.e., \"atrial functional regurgitation\") may require different treatment and interventional repair approaches than the classical functional regurgitation due to ventricular dilatation and dysfunction (\"ventricular functional regurgitation\"), and current guideline recommendations do not yet address this distinction. Clarifying the differences in the pathophysiology of atrial functional regurgitation and its management implications is of paramount importance. This review describes briefly the comparative anatomy of mitral and tricuspid apparatus and the pathophysiology and typical echocardiographic features of atrial functional regurgitation compared with ventricular functional regurgitation, as well as the added value of three-dimensional echocardiography as an essential imaging tool to clarify the mechanisms involved in its development.

Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 31 Oct 2019; epub ahead of print
Muraru D, Guta AC, Ochoa-Jimenez RC, Bartos D, ... Basso C, Badano LP
J Am Soc Echocardiogr: 31 Oct 2019; epub ahead of print | PMID: 31685293
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Abstract

Concentric vs. eccentric remodelling in heart failure with reduced ejection fraction: clinical characteristics, pathophysiology and response to treatment.

Nauta JF, Hummel YM, Tromp J, Ouwerkerk W, ... van Melle JP, Voors AA
Aims
Heart failure is traditionally classified by left ventricular ejection fraction (LVEF), rather than by left ventricular (LV) geometry, with guideline-recommended therapies in heart failure with reduced ejection fraction (HFrEF) but not heart failure with preserved ejection fraction (HFpEF). Most patients with HFrEF have eccentric LV hypertrophy, but some have concentric LV hypertrophy. We aimed to compare clinical characteristics, biomarker patterns, and response to treatment of patients with HFrEF and eccentric vs. concentric LV hypertrophy.
Methods and results
We performed a retrospective post-hoc analysis including 1015 patients with HFrEF (LVEF <40%) from the multinational observational BIOSTAT-CHF study. LV geometry was classified using two-dimensional echocardiography. Network analysis of 92 biomarkers was used to investigate pathophysiologic pathways. Concentric LV hypertrophy was present in 142 (14%) patients, who were on average older and more likely hypertensive compared to those with eccentric LV hypertrophy. Network analysis revealed that N-terminal pro-B-type natriuretic peptide was an important hub in eccentric hypertrophy, whereas in concentric hypertrophy, tumour necrosis factor receptor 1, urokinase plasminogen activator surface receptor, paraoxonase and P-selectin were central hubs. Up-titration of beta-blockers was associated with a mortality benefit in HFrEF with eccentric but not concentric LV hypertrophy (P-value for interaction ≤0.001). For angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the hazard ratio for mortality was higher in concentric hypertrophy, but the interaction was not significant.
Conclusion
Patients with HFrEF with concentric hypertrophy have a clinical and biomarker phenotype that is distinctly different from those with eccentric hypertrophy. Patients with concentric hypertrophy may not experience similar benefit from up.-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers compared to patients with eccentric hypertrophy.

© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 10 Nov 2019; epub ahead of print
Nauta JF, Hummel YM, Tromp J, Ouwerkerk W, ... van Melle JP, Voors AA
Eur J Heart Fail: 10 Nov 2019; epub ahead of print | PMID: 31713324
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Abstract

Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome.

Cade WT, Laforest R, Bohnert KL, Reeds DN, ... Gropler RJ, Peterson LR
Background
Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function.
Methods/results
Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of O-water and 1-C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging. LV function and cardiac high-energy phosphate metabolism were examined via echocardiography and P magnetic resonance spectroscopy, respectively. Myocardial glucose extraction fraction (21 ± 14% vs 10 ± 8%, P = .03) and glucose utilization (828.0 ± 470.0 vs 393.2 ± 361.0 μmol·g·min, P = .02) were significantly higher in BTHS vs Control. Myocardial FA extraction fraction (31 ± 7% vs 41 ± 6%, P < .002) and uptake (0.25 ± 0.04 vs 0.29 ± 0.03 mL·g·min, P < .002) were significantly lower in BTHS vs Control. Altered myocardial metabolism was associated with lower cardiac function in BTHS.
Conclusions
Myocardial substrate metabolism is altered and may contribute to LV dysfunction in BTHS. Clinical Trials #: NCT01625663.



J Nucl Cardiol: 07 Nov 2019; epub ahead of print
Cade WT, Laforest R, Bohnert KL, Reeds DN, ... Gropler RJ, Peterson LR
J Nucl Cardiol: 07 Nov 2019; epub ahead of print | PMID: 31705425
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Impact:
Abstract

Left ventricular apical pacing in children: feasibility and long-term effect on ventricular function.

Kovanda J, Ložek M, Ono S, Kubuš P, Tomek V, Janoušek J
Aims 
Left ventricular apical pacing (LVAP) has been reported to preserve left ventricular (LV) function in chronically paced children with complete atrioventricular block (CAVB). We sought to evaluate long-term feasibility of LVAP and the effect on LV mechanics and exercise capacity as compared to normal controls.
Methods and results 
Thirty-six consecutive paediatric patients with CAVB and LVAP in the absence (N = 22) or presence of repaired structural heart disease (N = 14, systemic LV in all) and 25 age-matched normal controls were cross-sectionally studied after a median of 3.9 (interquartile range 2.1-6.8) years of pacing using echocardiography and exercise stress testing. Pacemaker implantation was uneventful and there was no death. Probability of the absence of pacemaker-related surgical revision (elective generator replacement excluded) was 89.0% at 5 years after implantation. Left ventricular apical pacing patients had lower maximum oxygen uptake (P = 0.009), no septal to lateral but significant apical to basal LV mechanical delay (P < 0.001) which correlated with decreased LV contraction efficiency (P = 0.001). Left ventricular ejection fraction and global longitudinal LV strain were, however, not different from controls. Results were similar in both the presence and absence of structural heart disease.
Conclusion 
Left ventricular apical pacing is technically feasible with a low reintervention rate. Mechanical synchrony between LV septum and free wall is maintained at the price of an apical to basal mechanical delay associated with LV contraction inefficiency as compared to healthy controls. Global LV systolic function is, however, not negatively affected by LVAP.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Europace: 05 Dec 2019; epub ahead of print
Kovanda J, Ložek M, Ono S, Kubuš P, Tomek V, Janoušek J
Europace: 05 Dec 2019; epub ahead of print | PMID: 31808515
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Abstract

Appropriate coronary revascularization can be accomplished if myocardial perfusion is quantified by positron emission tomography prior to treatment decision.

Akil S, Hedeer F, Oddstig J, Olsson T, ... Hindorf C, Engblom H
Background
Many patients undergo percutaneous coronary intervention (PCI) without the use of non-invasive stress testing prior to treatment. The aim of this study was to determine the potential added value of guiding revascularization by quantitative assessment of myocardial perfusion prior to intervention.
Methods and results
Thirty-three patients (10 females) with suspected or established CAD who had been referred for a clinical coronary angiography (CA) with possibility for PCI were included. Adenosine stress and rest N-NH PET, cardiac magnetic resonance (CMR), and cardiopulmonary exercise test were performed 4 ± 3 weeks before and 5 ± 1 months after CA. The angiographer was blinded to the PET and CMR results. Myocardial flow reserve (MFR) < 2.0 by PET was considered abnormal. A PCI was performed in 19/33 patients. In 41% (11/27) of the revascularized vessel territories, a normal regional MFR was found prior to the PCI and no improvement in MFR was found at follow-up (P = 0.9). However, vessel territories with regional MFR < 2.0 at baseline improved significantly after PCI (P = 0.003). Of the 14 patients not undergoing PCI, four had MFR < 2.0 in one or more coronary territories.
Conclusion
Assessment of quantitative myocardial perfusion prior to revascularization could lead to more appropriate use of CA when managing patients with stable CAD.



J Nucl Cardiol: 07 Nov 2019; epub ahead of print
Akil S, Hedeer F, Oddstig J, Olsson T, ... Hindorf C, Engblom H
J Nucl Cardiol: 07 Nov 2019; epub ahead of print | PMID: 31705424
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Impact:
Abstract

Successful treatment of a paravalvular leak with balloon cracking and valve-in-valve TAVR.

Ruge H, Erlebach M, Lieberknecht E, Lange R

Transcatheter heart valve implantation into degenerated bioprosthetic valves (ViV-THV implantation) has become an established procedure for high risk patients. In general, paravalvular leak (PVL) is a contraindication for valve-in-valve-TAVR (ViV-TAVR). Herein, we report on a 81-year-old patient presenting with acute heart failure for a failing aortic bioprosthesis (Medtronic Mosaic 27 mm). Intraoperative transesophageal echocardiography during urgent ViV-TAVR revealed a PVL previously not detected. After transfemoral implantation of a 26 mm-Evolut-R, balloon-fracturing of the bioprosthetic ring was performed using a 24 mm True Dilatation balloon for treatment of the PVL. Afterward, left ventricular to aortic peak-to-peak pressure gradient measured 2-4mmHg. Transesophageal echocardiography merely revealed trace PVL. Aortic root angiography showed no PVL. At discharge, echocardiography measured a transprosthetic mean gradient of 5mmHg detecting no PVL. Intentional ring-fracturing of an aortic valve prostheses may prove not only to be effective in lowering transvalvular gradients after valve-in-valve-TAVR, but may also be a tool to treat PVL alongside degenerated surgical aortic bioprostheses in certain patients.

© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 02 Dec 2019; epub ahead of print
Ruge H, Erlebach M, Lieberknecht E, Lange R
Catheter Cardiovasc Interv: 02 Dec 2019; epub ahead of print | PMID: 31794136
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Impact:
Abstract

Left atrial structure and function and the risk of death or heart failure in atrial fibrillation.

Inciardi RM, Giugliano RP, Claggett B, Gupta DK, ... Solomon SD,
Aims
The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular (CV) death or heart failure (HF) hospitalization in a population with atrial fibrillation (AF).
Methods and results
In a prospective echocardiographic substudy of the Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study, 971 patients underwent transthoracic echocardiography. The associations between LA structure (LA volume index [LAVi]) and function (LA emptying fraction [LAEF] and LA expansion index [LAEi]) and risk for the composite endpoint of CV death or HF hospitalization, and its components, were assessed. Over a median follow-up of 2.5 years, 142 patients (14.6%) experienced CV death or HF hospitalization. Higher LAVi and lower LAEF and LAEi were each associated with a higher unadjusted risk for the composite outcome and its components. After adjustment for clinical and echocardiographic confounders, only measures of impaired LA function were predictive of the composite outcome (hazard ratio [HR] per 1 standard deviation [SD] decrease in LAEF: 1.35; 95% confidence interval [CI] 1.09-1.67 [P = 0.005]; HR per 1 SD decrease in LAEi: 1.34; 95% CI 1.06-1.69 [P = 0.012]). These findings were similar regardless of left ventricular ejection fraction, history of HF or whether patients were in AF or sinus rhythm at the time of the echocardiographic examination.
Conclusions
In patients with AF, LA dysfunction was significantly associated with an increased risk for CV death or HF hospitalization and was more predictive of these outcomes than LA size. These parameters may help to identify AF patients at greatest risk for the development of HF.
Clinical trial registration
ClinicalTrials.gov, NCT00781391.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Eur J Heart Fail: 26 Nov 2019; epub ahead of print
Inciardi RM, Giugliano RP, Claggett B, Gupta DK, ... Solomon SD,
Eur J Heart Fail: 26 Nov 2019; epub ahead of print | PMID: 31777160
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Impact:
Abstract

Percutaneous closure of restrictive-type perimembranous ventricular septal defect using the new KONAR multifunctional occluder: Midterm outcomes of the first middle-eastern experience.

Haddad RN, Daou LS, Saliba ZS
Objectives
To evaluate the safety, efficiency, and midterm outcomes of transcatheter perimembranous ventricular septal defect (pmVSD) closure using the new KONAR-MF™ VSD occluder.
Background
Off-label percutaneous pmVSD closure is a well-established procedure with promising results. Yet, interventionists are still searching for the ideal device.
Methods
Between June 2018 and March 2019, 20 patients with hemodynamically significant but restrictive-type pmVSD underwent an attempted transcatheter closure using the new KONAR-MF™. All implantations were performed retrogradely under general anesthesia, transoesophageal echocardiography, and fluoroscopic guidance. Prospective follow-up using transthoracic echocardiography and electrocardiogram was done until August 2019.
Results
The median age was 6.4 years (8 months to 43.4 years), and the median body weight was 17.3 (9-74) kg. The mean defect size on the left ventricular aspect was 11.7 ± 2.8 mm. All devices were successfully and rapidly implanted. One device embolized in the pulmonary artery, 24 hr after implantation and was percutaneously retrieved with no complication. Over a mean follow-up period of 8.2 ± 3.0 months, complete closure was achieved in 84.2% of patients. One new onset of mild aortic regurgitation was detected before discharge and remained stable. Tricuspid valve regurgitation, complete heart block, major complication, and death were not observed.
Conclusions
Transcatheter pmVSD closure using the KONAR-MF™ can be successfully performed in adult and pediatric patients. It is a safe and promising device, designed to provide high conformability to septal defects with a lower risk of heart block. Retrograde implantation allows procedural flexibility, efficient deliverability, and control of valvular interferences.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 29 Dec 2019; epub ahead of print
Haddad RN, Daou LS, Saliba ZS
Catheter Cardiovasc Interv: 29 Dec 2019; epub ahead of print | PMID: 31886940
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Impact:
Abstract

Evaluation of Cardiac Function in Women With a History of Preeclampsia: A Systematic Review and Meta-Analysis.

Reddy M, Wright L, Rolnik DL, Li W, ... Wallace EM, Palmer K

Background Women with a history of preeclampsia are at increased risk of cardiovascular morbidity and mortality. However, the underlying mechanisms of disease association, and the ideal method of monitoring this high-risk group, remains unclear. This review aims to determine whether women with a history of preeclampsia show clinical or subclinical cardiac changes when evaluated with an echocardiogram. Methods and Results A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify studies that examined cardiac function in women with a history of preeclampsia, in comparison with those with normotensive pregnancies. In the 27 included studies, we found no significant differences between preeclampsia and nonpreeclampsia women with regard to left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. Women with a history of preeclampsia demonstrated a higher left ventricular mass index and relative wall thickness with a mean difference of 4.25 g/m (95% CI, 2.08, 6.42) and 0.03 (95% CI, 0.01, 0.05), respectively. In comparison with the nonpreeclampsia population, they also demonstrated a lower E/A and a higher E/e\' ratio with a mean difference of -0.08 (95% CI, -0.15, -0.01) and 0.84 (95% CI, 0.41, 1.27), respectively. Conclusions In comparison with women who had a normotensive pregnancy, women with a history of preeclampsia demonstrated a trend toward altered cardiac structure and function. Further studies with larger sample sizes and consistent echocardiogram reporting with the use of sensitive preclinical markers are required to assess the role of echocardiography in monitoring this high-risk population group.



J Am Heart Assoc: 18 Nov 2019; 8:e013545
Reddy M, Wright L, Rolnik DL, Li W, ... Wallace EM, Palmer K
J Am Heart Assoc: 18 Nov 2019; 8:e013545 | PMID: 31698969
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Impact:
Abstract

Long-term effects of Na /Ca exchanger inhibition with ORM-11035 improves cardiac function and remodelling without lowering blood pressure in a model of heart failure with preserved ejection fraction.

Primessnig U, Bracic T, Levijoki J, Otsomaa L, ... Pieske B, Heinzel FR
Aims
Heart failure with preserved ejection fraction (HFpEF) is increasingly common but there is currently no established pharmacological therapy. We hypothesized that ORM-11035, a novel specific Na /Ca exchanger (NCX) inhibitor, improves cardiac function and remodelling independent of effects on arterial blood pressure in a model of cardiorenal HFpEF.
Methods and results
Rats were subjected to subtotal nephrectomy (NXT) or sham operation. Eight weeks after intervention, treatment for 16 weeks with ORM-11035 (1 mg/kg body weight) or vehicle was initiated. At 24 weeks, blood pressure measurements, echocardiography and pressure-volume loops were performed. Contractile function, Ca transients and NCX-mediated Ca extrusion were measured in isolated ventricular cardiomyocytes. NXT rats (untreated) showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV end-diastolic pressure (LVEDP) elevation, increased brain natriuretic peptide (BNP) levels, preserved ejection fraction and pulmonary congestion. In cardiomyocytes from untreated NXT rats, early relaxation was prolonged and NCX-mediated Ca extrusion was decreased. Chronic treatment with ORM-11035 significantly reduced LV hypertrophy and cardiac remodelling without lowering systolic blood pressure. LVEDP [14 ± 3 vs. 9 ± 2 mmHg; NXT (n = 12) vs. NXT + ORM (n = 12); P = 0.0002] and BNP levels [71 ± 12 vs. 49 ± 11 pg/mL; NXT (n = 12) vs. NXT + ORM (n = 12); P < 0.0001] were reduced after ORM treatment. LV cardiomyocytes from ORM-treated rats showed improved active relaxation and diastolic cytosolic Ca decay as well as restored NCX-mediated Ca removal, indicating NCX modulation with ORM-11035 as a promising target in the treatment of HFpEF.
Conclusion
Chronic inhibition of NCX with ORM-11035 significantly attenuated cardiac remodelling and diastolic dysfunction without lowering systemic blood pressure in this model of HFpEF. Therefore, long-term treatment with selective NCX inhibitors such as ORM-11035 should be evaluated further in the treatment of heart failure.

© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 23 Nov 2019; epub ahead of print
Primessnig U, Bracic T, Levijoki J, Otsomaa L, ... Pieske B, Heinzel FR
Eur J Heart Fail: 23 Nov 2019; epub ahead of print | PMID: 31762174
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Impact:
Abstract

Left Ventricular Longitudinal Strain as a Marker for Point of No Return in Hypertensive Heart Failure Treatment.

Ishizu T, Seo Y, Namekawa M, Murakoshi N, Ieda M, Kawakami Y
Background
There are currently no therapies that can improve prognosis in cases of heart failure (HF) with preserved ejection fraction (EF). We hypothesized that there is a point of no return after which no response to treatment is noted and that for the prevention of hypertensive HF this point may be determined by left ventricle (LV) strain, in the prevention of hypertensive HF. Here an angiotensin-converting enzyme inhibitor (ACE-I) was initiated based on myocardial strain imaging and its effects were determined in an animal model.
Methods
Thirty-two male Dahl salt-sensitive rats, age 6 weeks, were divided into six experimental groups and compared with low-salt (n = 8) and high-salt control groups (n = 8). In the early treatment group, ACE-I was administered from the age of 6 weeks (n = 4); in the longitudinal strain (LS) group, at 10-12 weeks when LS impairment was >-21% (n = 4); in the circumferential strain (CS) group, at 16-18 weeks when CS impairment was >-18% (n = 4); and in the EF group, at 20 weeks when EF was <55% (n = 4). Subsequently, all rats were sacrificed at 23 weeks age, the LV and lung weight were measured, and pathologic analyses were performed.
Results
At 23 weeks of age, the lung and LV weights increased in the high-salt control, EF, and CS groups, whereas the lung and LV weights in the LS and early groups were similar to those in the low-salt control group. The percentage of area of subendocardial fibrosis was >6% in the high-salt control, EF, and CS groups and <3% in the LS, early, and low-salt groups. Serial echocardiography demonstrated LS improvement in the LS group; however, the CS and EF groups showed no differences.
Conclusions
Heart failure-related lung congestion was prevented when ACE-I was administered soon after LS impairment, accompanied by suppression of cardiac hypertrophy and fibrosis, thereby suggesting that the point of no return of myocardial remodeling due to hypertension was present after LS but before CS impairment.

Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 14 Nov 2019; epub ahead of print
Ishizu T, Seo Y, Namekawa M, Murakoshi N, Ieda M, Kawakami Y
J Am Soc Echocardiogr: 14 Nov 2019; epub ahead of print | PMID: 31740371
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Impact:
Abstract

Effect of postdilatation following balloon expandable transcatheter aortic valve implantation.

Kawaguchi T, Yamaji K, Ishizu K, Morinaga T, ... Shirai S, Ando K
Background
Postdilatation after transcatheter heart valve (THV) implantation was associated with larger aortic valve areas in large-scale registries; however, the specific effects of postdilatation are poorly understood.
Methods and results
Among a total of 224 consecutive patients who underwent transcatheter aortic valve replacement using SAPIEN 3, 121 patients (54.0%) underwent postdilatation (same contrast volume: N = 101, +1 ml: N = 17, +2 ml: N = 3). THV diameter was assessed (a) during, (b) after implantation, (c) during postdilatation, and (d) after postdilatation by quantitative fluoroscopy. In the overall patients (N = 224), acute recoil was observed from during implantation (23.0 ± 2.0 mm) to after implantation (22.5 ± 2.0 mm, p < .001) with an absolute recoil of 0.52 ± 0.25 mm. After postdilatation (N = 121), THV diameter significantly increased from 22.5 ± 2.0 mm to 22.9 ± 2.1 mm (p < .001), with smaller absolute recoil (0.39 ± 0.21 mm, p < .001). Compared with those who did not undergo postdilatation, patients who underwent postdilatation had larger postprocedural THV area assessed by multi-slice computed tomography (471.4 ± 78.1 mm vs. 447.5 ± 76.3 mm , p = .02) and larger effective orifice area (EOA) assessed by echocardiography throughout 1 year (at 30 day, 1.66 ± 0.33 cm vs. 1.45 ± 0.27 cm , p < .001; at 6 month, 1.66 ± 0.33 cm vs. 1.44 ± 0.29 cm , p < .001; at 1 year, 1.69 ± 0.38 cm vs. 1.47 ± 0.30 cm , p < .001).
Conclusions
Postdilatation after implantation of the SAPIEN 3 valve produced a larger THV diameter with less acute recoil, followed by larger EOA throughout 1 year. Further studies are needed to evaluate the impact of postdilatation on long-term clinical outcomes.

© 2019 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 26 Dec 2019; epub ahead of print
Kawaguchi T, Yamaji K, Ishizu K, Morinaga T, ... Shirai S, Ando K
Catheter Cardiovasc Interv: 26 Dec 2019; epub ahead of print | PMID: 31880388
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Impact:
Abstract

Mitral regurgitation, left atrial structural and functional remodelling and the effect on pulmonary haemodynamics.

Inciardi RM, Rossi A, Bergamini C, Benfari G, ... Ribichini FL, Cicoira M
Aims
To assess the association between mitral regurgitation (MR) and left atrial (LA) structural and functional remodelling and their effect on pulmonary haemodynamics.
Methods and results
Consecutive unselected patients undergoing comprehensive echocardiography were enrolled. Parameters of cardiac structure and function were obtained as well as mitral effective regurgitant orifice area (ERO) and estimation of pulmonary artery systolic pressure (PASP). Measures of LA structure [LA volume (LAV)] and function [peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and conduit strain (CS)] were also calculated. The study population included 102 patients (mean age 70 ± 14 years, 42% women), with a mean ejection fraction of 52 ± 13%. MR was classified as organic due to mitral valve prolapse in 14 patients (14%) and functional in 88 patients (86%). Mean ERO was 0.12 ± 0.12 cm and 86 patients (84%) had an ERO ≤0.2 cm . ERO was significantly associated with worse measures of LA structure and function. Despite the low burden of MR, the association remained significant after adjusting for clinical and echocardiographic confounders (β: 3.7, P = 0.022 for LAV; β: -3.0, P = 0.003 for PALS; β: -1.8, P = 0.027 for PACS) and was significantly related with functional MR (P for interaction <0.001). ERO was also significantly associated with PASP, and measures of LA function (PALS and PACS) significantly modified this relationship (P for interaction <0.001).
Conclusions
Even a mild degree of MR contributes to LA remodelling and this relationship plays an active role in pulmonary circulation, suggesting a potential mechanism by which these parameters contribute to the development of heart failure.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Eur J Heart Fail: 01 Dec 2019; epub ahead of print
Inciardi RM, Rossi A, Bergamini C, Benfari G, ... Ribichini FL, Cicoira M
Eur J Heart Fail: 01 Dec 2019; epub ahead of print | PMID: 31793154
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Impact:
Abstract

Baseline Right Ventricular Dysfunction Predicts Worse Outcomes in Patients Undergoing Cardiac Resynchronization Therapy (CRT) Implantation.

Patel D, Trulock K, Kumar A, Kiehl E, ... Wilkoff B, Rickard J
Introduction
Cardiac resynchronization therapy (CRT) has been shown to improve survival in patients with systolic heart failure, wide QRS duration, and left-bundle-branch-block (LBBB). However, CRT outcomes stratified by right ventricular (RV) function at implant have not been well studied.
Methods
We retrospectively reviewed patients at Cleveland Clinic who underwent CRT implantation (n=777) from 2003-2011 with a diagnosis of heart failure, echocardiography with both pre-CRT LVEF ≤ 35 percent and available post-CRT echocardiography at 6 months post-implant. CRT response was defined as LVEF improvement ≥ 5%. Patients were separated into 2 groups: normal or mild RV dysfunction (n=570) labeled NORMAL RV; moderate to severe dysfunction (n=207) labeled RV DYSFXN based on qualitative echocardiography assessment. Survival was calculated as time from CRT implant to death, LVAD implant, or heart transplant.
Results
CRT response was significantly higher in patients with NORMAL RV (67%) compared to patients with RV DYSFXN (56%) (p=0.006). Kaplan-Meier analysis showed that CRT patients with NORMAL RV had significantly greater survival compared to patients with RV DYSFXN (p <0.001). In multivariable Cox regression accounting for a priori co-variates, RV DYSFXN was associated with worse survival (HR 1.41 (95% CI 1.14-1.75) p=0.002) and lower CRT response (HR 0.66 (95%CI 0.44-0.97) p=0.03).
Conclusion
Baseline RV dysfunction at CRT implant is an important predictor of worsened left ventricular remodeling and survival in CRT patients.

Copyright © 2019. Published by Elsevier Inc.

J Card Fail: 23 Dec 2019; epub ahead of print
Patel D, Trulock K, Kumar A, Kiehl E, ... Wilkoff B, Rickard J
J Card Fail: 23 Dec 2019; epub ahead of print | PMID: 31881279
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Impact:
Abstract

Real-World Outcomes of Ventricular Tachycardia Catheter Ablation with versus without Intracardiac Echocardiography.

Field ME, Gold MR, Reynolds MR, Goldstein L, ... Khanna R, Winterfield JR
Introduction
By providing real-time monitoring of catheter-tissue interface and for complications, intracardiac echocardiography (ICE) during catheter ablation for ventricular tachycardia (VT) may improve outcomes. To test this hypothesis, we compared 12-month readmission rates (all-cause, cardiovascular [CV]-related, VT-related), repeat ablation and complications among VT patients with structural heart disease undergoing ablation with versus without ICE.
Methods and results
Using the 2008-2017 IBM MarketScan® Commercial and Medicare Supplemental databases, patients with a history of implantable cardioverter defibrillator/cardiac resynchronization therapy (ICD/CRT-D) who underwent VT ablation with and without ICE use were identified. Propensity matching was performed and regression analysis was used to compare outcomes. After matching, 1,324 patients were identified (ICE: 662; non-ICE: 662). The rate of 12-month VT-related readmission (18.13% vs 22.51%; p < 0.05) and repeat VT ablation (14.35% vs 19.34%; p = 0.02) post-index discharge were lower among patients in the ICE group compared to the non-ICE group, with a 24% lower risk of 12-month VT-related readmission (OR 0.76; 95% CI 0.58-0.99) and a 30% lower risk of repeat ablation (OR 0.70; 95% CI 0.52-0.93) versus non-ICE group. The 12-month all-cause (44.56% vs 43.20%; p = 0.62) and CV-related readmissions (35.20% vs 32.93%; p = 0.38) and complication rates were not significantly different between the two groups.
Conclusions
VT ablation using ICE was associated with a lower likelihood of 12-month VT-related readmission and repeat ablation compared to non-ICE patients. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 22 Dec 2019; epub ahead of print
Field ME, Gold MR, Reynolds MR, Goldstein L, ... Khanna R, Winterfield JR
J Cardiovasc Electrophysiol: 22 Dec 2019; epub ahead of print | PMID: 31868258
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Impact:
Abstract

Imaging in patients with suspected acute heart failure: timeline approach position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

Čelutkienė J, Lainscak M, Anderson L, Gayat E, ... Rosano G, Seferovic P

Acute heart failure is one of the main diagnostic and therapeutic challenges in clinical practice due to a non-specific clinical manifestation and the urgent need for timely and tailored management at the same time. In this position statement, the Heart Failure Association aims to systematize the use of various imaging methods in accordance with the timeline of acute heart failure care proposed in the recent guidelines of the European Society of Cardiology. During the first hours of admission the point-of-care focused cardiac and lung ultrasound examination is an invaluable tool for rapid differential diagnosis of acute dyspnoea, which is highly feasible and relatively easy to learn. Several portable and stationary imaging modalities are being increasingly used for the evaluation of cardiac structure and function, haemodynamic and volume status, precipitating myocardial ischaemia or valvular abnormalities, and systemic and pulmonary congestion. This paper emphasizes the central role of the full echocardiographic examination in the identification of heart failure aetiology, severity of cardiac dysfunction, indications for specific heart failure therapy, and risk stratification. Correct evaluation of cardiac filling pressures and accurate prognostication may help to prevent unscheduled short-term readmission. Alternative advanced imaging modalities should be considered to assist patient management in the pre- and post-discharge phase, including cardiac magnetic resonance, computed tomography, nuclear studies, and coronary angiography. The Heart Failure Association addresses this paper to the wide spectrum of acute care and heart failure specialists, highlighting the value of all available imaging techniques at specific stages and in common clinical scenarios of acute heart failure.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Eur J Heart Fail: 08 Dec 2019; epub ahead of print
Čelutkienė J, Lainscak M, Anderson L, Gayat E, ... Rosano G, Seferovic P
Eur J Heart Fail: 08 Dec 2019; epub ahead of print | PMID: 31815347
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Impact:
Abstract

Functional mitral regurgitation and left atrial myopathy in heart failure with preserved ejection fraction.

Tamargo M, Obokata M, Reddy YNV, Pislaru SV, ... Nishimura RA, Borlaug BA
Aims
Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve.
Methods and results
Patients with HFpEF (n = 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n = 163), patients with MR-HFpEF (n = 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r = 0.63, P < 0.0001) but was only weakly related to left ventricular remodelling (r = 0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm.
Conclusions
Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

© 2020 The Authors. European Journal of Heart Failure © 2020 European Society of Cardiology.

Eur J Heart Fail: 06 Jan 2020; epub ahead of print
Tamargo M, Obokata M, Reddy YNV, Pislaru SV, ... Nishimura RA, Borlaug BA
Eur J Heart Fail: 06 Jan 2020; epub ahead of print | PMID: 31908127
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Impact:
Abstract

Endothelium-dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Yang JH, Obokata M, Reddy YNV, Redfield MM, Lerman A, Borlaug BA
Background
Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium-dependent and independent coronary microvascular function in HFpEF.
Methods and results
Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10 -10  mol/L) using a Doppler flow wire with quantitative angiography. Endothelium-independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium-dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium-independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co-morbidities or other clinical characteristics. As compared to patients with normal endothelium-independent function, HFpEF patients with endothelium-independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0 ± 1.8 vs. 8.4 ± 2.9 cm/s, P = 0.002) and higher estimated filling pressures (E/e\' 13.1 ± 4.1 vs. 9.6 ± 3.4, P < 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium-dependent coronary vasodilatation. Endothelium-independent microvascular dysfunction was associated with increased mortality.
Conclusions
Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium-dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co-morbidities alone. Patients with HFpEF and endothelium-independent microvascular dysfunction display worse diastolic dysfunction and outcomes.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Eur J Heart Fail: 14 Dec 2019; epub ahead of print
Yang JH, Obokata M, Reddy YNV, Redfield MM, Lerman A, Borlaug BA
Eur J Heart Fail: 14 Dec 2019; epub ahead of print | PMID: 31840366
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Impact:
Abstract

Assessing the evidence-practice gap for heart failure in China: the Heart Failure Registry of Patient Outcomes (HERO) study design and baseline characteristics.

Li L, Liu R, Jiang C, Du X, ... Li L, Dong J
Background
Registry studies in high-income countries have defined contemporary management of heart failure (HF), but few such data exist in the large aging population of China. We report the study design and baseline characteristics of the Heart Failure Registry of Patient Outcomes (HERO) study, undertaken to determine evidence-practice gaps in the management of HF in a broad and representative population of China.
Methods and results
The HERO study is a prospective, longitudinal, seasonally-rotating, multicentre registry study of patients hospitalized with acute HF who are followed up over 12 months. Patients were recruited on the basis of primary admission clinical diagnosis of acute HF at 73 hospitals in Henan, the largest and most socio-economically diverse province in China, from November 2017 to November 2018; follow-up is ongoing. For each patient, data obtained through interview and medial record review by independent clinical research staff include: socio-demographics, clinical features, diagnostic investigations, and treatment, with a subset of patients providing blood samples for future biomarker investigation. Surviving patients are scheduled to be followed up by telephone at 2 weeks, and 3, 6 and 12 months post-admission, or until death or study withdrawal. A total of 5620 patients (mean age 72 ± 12 years; 50% female) with acute HF were recruited from 8 provincial-, 22 municipal-, and 43 county-level hospitals. Patients had co-morbid hypertensive (48%), coronary (29%), or metabolic (20%) diseases. Among 3147 patients who had echocardiography, 54%, 20% and 25% of patients had ejection fraction of ≥50%, 40-50%, and < 40%, respectively. In-hospital or 3-day post-discharge mortality was 3.2% (182/5620). Death or readmission rate from the 4th day post-discharge to first follow-up (median 32 days) was 22.4% (977/4368).
Conclusions
The HERO study provides a unique opportunity to profile evidence-practice gaps across a broad spectrum of patients with acute HF in China.

© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 08 Dec 2019; epub ahead of print
Li L, Liu R, Jiang C, Du X, ... Li L, Dong J
Eur J Heart Fail: 08 Dec 2019; epub ahead of print | PMID: 31820513
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Impact:
Abstract

Bone marrow-derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4-year follow-up of the MSC-HF trial.

Mathiasen AB, Qayyum AA, Jørgensen E, Helqvist S, ... Ekblond A, Kastrup J
Aims
The study assessed 4-year outcomes of intramyocardial injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic heart failure.
Methods and results
The MSC-HF trial was a randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to intramyocardial injections of MSCs or placebo. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography. Sixty patients aged 30-80 years with ischaemic heart failure, New York Heart Association class II-III, left ventricular ejection fraction (LVEF) <45% and no further treatment options were randomized. Patients were followed clinically for 12 months and in addition 4-year data of hospitalizations and survival were retrieved. After 12 months, LVESV was significantly reduced in the MSC group and not in the placebo group, with difference between groups of 17.0 ± 16.2 mL (95% confidence interval 8.3-25.7, P = 0.0002). There were also significant improvements in LVEF of 6.2% (P < 0.0001), stroke volume of 16.1 mL (P < 0.0001) and myocardial mass (P = 0.009) between groups. A significant dose-response effect was also observed. Moreover, a significant reduction in the amount of scar tissue and quality of life score in the MSC group but not in the placebo group was observed. After 4 years, there were significantly fewer hospitalizations for angina in the MSC group and otherwise no differences in hospitalizations or survival. No side effects were identified.
Conclusions
Intramyocardial injections of autologous bone marrow-derived MSCs improved myocardial function and myocardial mass in patients with ischaemic heart failure.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Eur J Heart Fail: 20 Dec 2019; epub ahead of print
Mathiasen AB, Qayyum AA, Jørgensen E, Helqvist S, ... Ekblond A, Kastrup J
Eur J Heart Fail: 20 Dec 2019; epub ahead of print | PMID: 31863561
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Impact:
Abstract

Validation of Cardiovascular Magnetic Resonance-Derived Equation for Predicted Left Ventricular Mass Using the UK Biobank Imaging Cohort: Tool for Donor-Recipient Size Matching.

Fung K, Cheshire C, Cooper JA, Catarino P, ... Pettit S, Petersen SE
Background
Current guidance from International Society for Heart and Lung Transplantation recommends using body weight for donor-recipient size matching for heart transplantation. However, recent studies have shown that predicted heart mass, using body weight, height, age, and sex, may represent a better method of size matching. We aim to validate a cardiovascular magnetic resonance (CMR)-derived equation for predicted left ventricular mass (LVM) in a cohort of normal individuals in the United Kingdom.
Methods
This observational study was conducted in 5065 middle-aged (44-77 years old) UK Biobank participants who underwent CMR imaging in 2014 to 2015. Individuals with cancer diagnosis in the previous 12 months or history of cardiovascular disease were excluded. Predicted LVM was calculated based on participants\' sex, height, and weight recorded at the time of imaging. Correlation analyses were performed between the predicted LVM and the LVM obtained from manual contouring of CMR cine images. The analysis included 3398 participants (age 61.5±7.5 years, 47.8% males).
Results
Predicted LVM was considerably higher than CMR-derived LVM (mean±SD of 138.8±28.9 g versus 86.3±20.9 g). However, there was a strong correlation between the 2 measurements (Spearman correlation coefficient 0.802, <0.0001).
Conclusions
Predicted LVM calculated using a CMR-derived equation that incorporates height, weight, and sex has a strong correlation with CMR LVM in large cohort of normal individuals in the United Kingdom. Our findings suggest that predicted heart mass equations may be a valid tool for donor-recipient size matching for heart transplantation in the United Kingdom.



Circ Heart Fail: 29 Nov 2019; 12:e006362
Fung K, Cheshire C, Cooper JA, Catarino P, ... Pettit S, Petersen SE
Circ Heart Fail: 29 Nov 2019; 12:e006362 | PMID: 31805784
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Abstract

A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes.

Larsen AH, Jessen N, Nørrelund H, Tolbod LP, ... Sörensen J, Wiggers H
Aims
The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes.
Methods and results
Thirty-six HFrEF patients (ejection fraction 37 ± 8%; median age 66 years) were randomised to metformin (n = 19) or placebo (n = 17) for 3 months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed byC-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 ± 550 mg/day) increased WMI [absolute mean difference, 1.0 mmHg·mL·m ·10 ; 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6 mL O ·100 g ·min ; P = 0.014). Cardiac stroke work was preserved (-2 J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2 kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups.
Conclusion
Metformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.

© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.

Eur J Heart Fail: 20 Dec 2019; epub ahead of print
Larsen AH, Jessen N, Nørrelund H, Tolbod LP, ... Sörensen J, Wiggers H
Eur J Heart Fail: 20 Dec 2019; epub ahead of print | PMID: 31863557
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