Topic: Imaging

Abstract

Effect of Smoking on Outcomes of Primary PCI in Patients With STEMI.

Redfors B, Furer A, Selker HP, Thiele H, ... Ben-Yehuda O, Stone GW
Background
Smoking is a well-established risk factor for ST-segment elevation myocardial infarction (STEMI); however, once STEMI occurs, smoking has been associated with favorable short-term outcomes, an observation termed the \"smoker\'s paradox.\" It has been postulated that smoking might exert protective effects that could reduce infarct size, a strong independent predictor of worse outcomes after STEMI.
Objectives
The purpose of this study was to determine the relationship among smoking, infarct size, microvascular obstruction (MVO), and adverse outcomes after STEMI.
Methods
Individual patient-data were pooled from 10 randomized trials of patients with STEMI undergoing primary percutaneous coronary intervention. Infarct size was assessed at median 4 days by either cardiac magnetic resonance imaging or technetium-99m sestamibi single-photon emission computed tomography. Multivariable analysis was used to assess the relationship between smoking, infarct size, and the 1-year rates of death or heart failure (HF) hospitalization and reinfarction.
Results
Among 2,564 patients with STEMI, 1,093 (42.6%) were recent smokers. Smokers were 10 years younger and had fewer comorbidities. Infarct size was similar in smokers and nonsmokers (adjusted difference: 0.0%; 95% confidence interval [CI]: -3.3% to 3.3%; p = 0.99). Nor was the extent of MVO different between smokers and nonsmokers. Smokers had lower crude 1-year rates of all-cause death (1.0% vs. 2.9%; p < 0.001) and death or HF hospitalization (3.3% vs. 5.1%; p = 0.009) with similar rates of reinfarction. After adjustment for age and other risk factors, smokers had a similar 1-year risk of death (adjusted hazard ratio [adjHR]: 0.92; 95% CI: 0.46 to 1.84) and higher risks of death or HF hospitalization (adjHR: 1.49; 95% CI: 1.09 to 2.02) as well as reinfarction (adjHR: 1.97; 95% CI: 1.17 to 3.33).
Conclusions
In the present large-scale individual patient-data pooled analysis, recent smoking was unrelated to infarct size or MVO, but was associated with a worse prognosis after primary PCI in STEMI. The smoker\'s paradox may be explained by the younger age and fewer cardiovascular risk factors in smokers compared with nonsmokers.

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

J Am Coll Cardiol: 20 Apr 2020; 75:1743-1754
Redfors B, Furer A, Selker HP, Thiele H, ... Ben-Yehuda O, Stone GW
J Am Coll Cardiol: 20 Apr 2020; 75:1743-1754 | PMID: 32299585
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Abstract

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide in Elderly Patients With Valvular Heart Disease.

Zhang B, Xu H, Zhang H, Liu Q, ... Wu Y,
Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) may reflect early prognosis in patients with valvular heart disease (VHD).
Objectives
The aim of this study was to examine the association between NT-proBNP and mortality in elderly patients with VHD.
Methods
A total of 5,983 elderly patients (age ≥60 years) with moderate or severe VHD underwent echocardiography and NT-proBNP measurement. VHD examined included aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid regurgitation, and multivalvular heart disease. NT-proBNP ratio was defined as measured NT-proBNP relative to the maximal normal values specific to age and sex. Disease-specific thresholds were defined on the basis of penalized splines and maximally selected rank statistics.
Results
The cohort had a mean age of 71.1 ± 7.6 years. At 1-year follow-up, 561 deaths (9.4%) had occurred. In penalized splines, relative hazards showed a monotonic increase with greater NT-proBNP ratio for death with different VHDs (p < 0.001 for all) except mitral stenosis. Higher NT-proBNP ratio, categorized by disease-specific thresholds, was independently associated with mortality (overall adjusted hazard ratio: 1.99; 95% confidence interval: 1.76 to 2.24; p < 0.001). Different subtypes of VHD all incurred excess mortality with elevated NT-proBNP ratio, with the strongest association detected for aortic stenosis (adjusted hazard ratio: 10.5; 95% confidence interval: 3.9 to 28.27; p < 0.001). The addition of NT-proBNP ratio to the prediction algorithm including traditional risk factors improved outcome prediction (overall net reclassification index = 0.28; 95% CI: 0.24 to 0.34; p < 0.001; likelihood ratio test p < 0.001). Results remained consistent in patients under medical care, with normal left ventricular ejection fractions, and with primary VHD.
Conclusions
NT-proBNP provides incremental prognostic information for mortality in various VHDs. It could aid in risk stratification as a pragmatic and versatile biomarker in elderly patients.

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

J Am Coll Cardiol: 13 Apr 2020; 75:1659-1672
Zhang B, Xu H, Zhang H, Liu Q, ... Wu Y,
J Am Coll Cardiol: 13 Apr 2020; 75:1659-1672 | PMID: 32273031
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Abstract

Supracardiac atherosclerosis in embolic stroke of undetermined source: the underestimated source.

Ntaios G, Wintermark M, Michel P

The term \'embolic stroke of undetermined source\' (ESUS) is used to describe patients with a non-lacunar ischaemic stroke without any identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause. When the ESUS concept was introduced, covert atrial fibrillation was conceived to be the main underlying cause in the majority of ESUS patients. Another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch-collectively described as supracardiac atherosclerosis. There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than it was initially perceived. Advanced imaging methods are available to identify plaques which high embolic risk. The role of novel antithrombotic strategies in these patients needs to be assessed in randomized controlled trials. This review presents the evidence which points towards a major aetiological association between atherosclerotic plaques and ESUS, summarizes the imaging features which may aid to identify plaques more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk, and highlights the rationale for future research in this field.

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: 15 Apr 2020; epub ahead of print
Ntaios G, Wintermark M, Michel P
Eur Heart J: 15 Apr 2020; epub ahead of print | PMID: 32300781
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Abstract

Evaluation and Management of Premature Ventricular Complexes.

Marcus GM

Premature ventricular complexes (PVCs) are extremely common, found in the majority of individuals undergoing long-term ambulatory monitoring. Increasing age, a taller height, a higher blood pressure, a history of heart disease, performance of less physical activity, and smoking each predict a greater PVC frequency. Although the fundamental causes of PVCs remain largely unknown, potential mechanisms for any given PVC include triggered activity, automaticity, and reentry. PVCs are commonly asymptomatic but can also result in palpitations, dyspnea, presyncope, and fatigue. The history, physical examination, and 12-lead ECG are each critical to the diagnosis and evaluation of a PVC. An echocardiogram is indicated in the presence of symptoms or particularly frequent PVCs, and cardiac magnetic resonance imaging is helpful when the evaluation suggests the presence of associated structural heart disease. Ambulatory monitoring is required to assess PVC frequency. The prognosis of those with PVCs is variable, with ongoing uncertainty regarding the most informative predictors of adverse outcomes. An increased PVC frequency may be a risk factor for heart failure and death, and the resolution of systolic dysfunction after successful catheter ablation of PVCs demonstrates that a causal relationship can be present. Patients with no or mild symptoms, a low PVC burden, and normal ventricular function may be best served with simple reassurance. Either medical treatment or catheter ablation are considered first-line therapies in most patients with PVCs associated with symptoms or a reduced left ventricular ejection fraction, and patient preference plays a role in determining which to try first. If medical treatment is selected, either β-blockers or nondihydropyridine calcium channel blockers are reasonable drugs in patients with normal ventricular systolic function. Other antiarrhythmic drugs should be considered if those initial drugs fail and ablation has been declined, has been unsuccessful, or has been deemed inappropriate. Catheter ablation is the most efficacious approach to eradicate PVCs but may confer increased upfront risks. Original research remains necessary to identify individuals at risk for PVC-induced cardiomyopathy and to identify preventative and therapeutic approaches targeting the root causes of PVCs to maximize effectiveness while minimizing risk.



Circulation: 27 Apr 2020; 141:1404-1418
Marcus GM
Circulation: 27 Apr 2020; 141:1404-1418 | PMID: 32339046
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Abstract

Vulnerable plaques and patients: state-of-the-art.

Tomaniak M, Katagiri Y, Modolo R, Silva R, ... Serruys PW, Onuma Y

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term \'vulnerable plaque\' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of \'vulnerability\' of a specific lesion to the more comprehensive goal of identifying patient \'cardiovascular vulnerability\'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and \'local\' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of \'high-risk\' plaques occurring in \'vulnerable\' patients.

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: 12 May 2020; epub ahead of print
Tomaniak M, Katagiri Y, Modolo R, Silva R, ... Serruys PW, Onuma Y
Eur Heart J: 12 May 2020; epub ahead of print | PMID: 32402086
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Abstract

Cardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis: JACC Review Topic of the Week.

Hanna M, Ruberg FL, Maurer MS, Dispenzieri A, ... Witteles RM, Grogan M

Technetium-labeled cardiac scintigraphy (i.e., Tc-PYP scan) has been repurposed for the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Validated in cohorts of patients with heart failure and echocardiographic and/or cardiac magnetic resonance imaging findings suggestive of cardiac amyloidosis, cardiac scintigraphy can confirm the diagnosis of ATTR-CM only when combined with blood and urine testing to exclude a monoclonal protein. Multisocietal guidelines support the nonbiopsy diagnosis of ATTR-CM using cardiac scintigraphy, yet emphasize its use in the appropriate clinical context and the crucial need to rule out light chain amyloid cardiomyopathy. Although increased awareness of ATTR-CM and the advent of effective therapy have led to rapid adoption of diagnostic scintigraphy, there is heterogeneity in adherence to consensus guidelines. This perspective outlines clinical scenarios wherein findings on technetium-labeled cardiac scintigraphy have been misinterpreted, reviews causes of false-negative and false-positive results, and provides strategies to avoid costly and potentially fatal misdiagnoses.

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

J Am Coll Cardiol: 08 Jun 2020; 75:2851-2862
Hanna M, Ruberg FL, Maurer MS, Dispenzieri A, ... Witteles RM, Grogan M
J Am Coll Cardiol: 08 Jun 2020; 75:2851-2862 | PMID: 32498813
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Abstract

Cardiac Energetics in Patients with Aortic Stenosis and Preserved versus Reduced Ejection Fraction.

Peterzan MA, Clarke WT, Lygate CA, Lake HA, ... Rodgers C, Rider OJ

Why some but not all patients with severe AS (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and/or flux is associated with this transition.102 participants were recruited to five groups: moderate AS (ModAS, n=13), severe AS, LVEF ≥55% (SevAS-pEF, n=37), severe AS, LVEF<55% (SevAS-rEF, n=15), healthy volunteers with non-hypertrophied hearts with normal systolic function (NHv, n=30), and patients with non-hypertrophied, non-pressure loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (NHbx, n=7). All underwent CMR imaging and P magnetic resonance spectroscopy (MRS) for myocardial energetics. LV biopsies (AS and NHBx) were analysed for; CK total activity, CK isoforms, citrate synthase (CS) activity and total creatine. Using serial block-face scanning electron microscopy, mitochondria-sarcomere diffusion distances were calculated.In the absence of failure, CK flux was lower in the presence of AS (by 32%, p=0.04), driven primarily by reduction in PCr/ATP (by 17%, p <0.001), with CK k unchanged (p=0.46),and is present in ModAS. Although lowest in the SevAS-rEF group, CK flux was not different to the SevAS-pEF group (p>0.99). Accompanying the fall in CK flux, total CK and CS activities, and absolute activities of MtCK and CK-MM were also lower (p<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (r=0.86, p=.003).Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo MRS measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, but where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS, and suggest a fall in CK flux is not per se the cause of transition to systolic failure. However, as ATP demands increase with AS severity this could increase susceptibility to systolic failure. As such, targeting CK capacity and/or flux may be a therapeutic strategy to prevent/treat systolic failure in AS.



Circulation: 21 May 2020; epub ahead of print
Peterzan MA, Clarke WT, Lygate CA, Lake HA, ... Rodgers C, Rider OJ
Circulation: 21 May 2020; epub ahead of print | PMID: 32438845
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Abstract

Pulmonary Hypertension Due to Left Heart Disease: Diagnosis, Pathophysiology, and Therapy.

Al-Omary MS, Sugito S, Boyle AJ, Sverdlov AL, Collins NJ

Pulmonary hypertension (PH) due to left heart disease (LHD) is the most common type of PH and is defined as mean pulmonary artery systolic pressure of >20 mm Hg and pulmonary capillary wedge pressure >15 mm Hg during right heart catheterization. LHD may lead to elevated left atrial pressure alone, which in the absence of intrinsic pulmonary vascular disease will result in PH without changes in pulmonary vascular resistance. Persistent elevation in left atrial pressure may, however, also be associated with subsequent pulmonary vascular remodeling, vasoconstriction, and an increase in pulmonary vascular resistance. Hence, there are 2 subgroups of PH due to LHD, isolated postcapillary PH and combined post- and precapillary PH, with these groups have differing clinical implications. Differentiation of pulmonary arterial hypertension and PH due to LHD is critical to guide management planning; however, this may be challenging. Older patients, patients with metabolic syndrome, and patients with imaging and clinical features consistent with left ventricular dysfunction are suggestive of LHD etiology rather than pulmonary arterial hypertension. Hemodynamic measures such as diastolic pressure gradient, transpulmonary gradient, and pulmonary vascular resistance may assist to differentiate pre- from postcapillary PH and offer prognostic insights. However, these are influenced by fluid status and heart failure treatment. Pulmonary arterial hypertension therapies have been trialed in the treatment with concerning results reflecting disease heterogeneity, variation in inclusion criteria, and mixed end point criteria. The aim of this review is to provide an updated definition, discuss possible pathophysiology, clinical aspects, and the available treatment options for PH due to LHD.



Hypertension: 26 Apr 2020:HYPERTENSIONAHA11914330; epub ahead of print
Al-Omary MS, Sugito S, Boyle AJ, Sverdlov AL, Collins NJ
Hypertension: 26 Apr 2020:HYPERTENSIONAHA11914330; epub ahead of print | PMID: 32336230
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Abstract

Loss of Protease-Activated Receptor 4 Prevents Inflammation Resolution and Predisposes the Heart to Cardiac Rupture after Myocardial Infarction.

Kolpakov MA, Guo X, Rafiq K, Vlasenko L, ... Houser SR, Sabri A

Cardiac rupture is a major lethal complication of acute myocardial infarction (MI). Despite significant advances in reperfusion strategies, mortality from cardiac rupture remains high. Studies suggest that cardiac rupture can be accelerated by thrombolytic therapy, but the relevance of this risk factor remains controversial.We analyzed protease activated receptor (Par)4 expression in mouse hearts with MI and investigated the effects of Par4 deletion on cardiac remodeling and function post-MI by echocardiography, quantitative immunohistochemistry and flow cytometry.Par4 mRNA and protein levels were increased in mouse hearts after MI and in isolated cardiomyocytes in response to hypertrophic and inflammatory stimuli. Par4-deficient mice showed less myocyte apoptosis, reduced infarct size and improved functional recovery after acute MI relative to wild-type (WT). Conversely, Par4 mice showed impaired cardiac function, greater rates of myocardial rupture and increased mortality after chronic MI relative to WT. Pathological evaluation of hearts from Par4 mice demonstrated a greater infarct expansion, increased cardiac hemorrhage and delayed neutrophil accumulation, which resulted in impaired post-MI healing compared to WT. Par4 deficiency also attenuated neutrophil apoptosisand after MIand impaired inflammation resolution in infarcted myocardium. Transfer of Par4 neutrophils, but not of Par4 platelets, in WT recipient mice delayed inflammation resolution, increased cardiac hemorrhage and enhanced cardiac dysfunction. In parallel, adoptive transfer of WT neutrophils into Par4 mice restored inflammation resolution, reduced cardiac rupture incidence and improved cardiac function post-MI.These findings reveal essential roles of Par4 in neutrophil apoptosis and inflammation resolution during myocardial healing and point to Par4 inhibition as potential therapy that should be limited to the acute phases of ischemic insult and to be avoided for chronic treatment post-MI.



Circulation: 02 Jun 2020; epub ahead of print
Kolpakov MA, Guo X, Rafiq K, Vlasenko L, ... Houser SR, Sabri A
Circulation: 02 Jun 2020; epub ahead of print | PMID: 32489148
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Abstract

Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis.

Yang Y, Li W, Zhu H, Pan XF, ... Cai X, Huang Y
Objective
To evaluate the prognosis of unrecognised myocardial infarction determined by electrocardiography (UMI-ECG) or cardiac magnetic resonance imaging (UMI-CMR).
Design
Systematic review and meta-analysis of prospective studies.
Data sources
Electronic databases, including PubMed, Embase, and Google Scholar.
Study selection
Prospective cohort studies were included if they reported adjusted relative risks, odds ratios, or hazard ratios and 95% confidence intervals for all cause mortality or cardiovascular outcomes in participants with unrecognised myocardial infarction compared with those without myocardial infarction.
Data extraction and synthesis
The primary outcomes were composite major adverse cardiac events, all cause mortality, and cardiovascular mortality associated with UMI-ECG and UMI-CMR. The secondary outcomes were the risks of recurrent coronary heart disease or myocardial infarction, stroke, heart failure, and atrial fibrillation. Pooled hazard ratios and 95% confidence intervals were reported. The heterogeneity of outcomes was compared in clinically recognised and unrecognised myocardial infarction.
Results
The meta-analysis included 30 studies with 253 425 participants and 1 621 920 person years of follow-up. UMI-ECG was associated with increased risks of all cause mortality (hazard ratio 1.50, 95% confidence interval 1.30 to 1.73), cardiovascular mortality (2.33, 1.66 to 3.27), and major adverse cardiac events (1.61, 1.38 to 1.89) compared with the absence of myocardial infarction. UMI-CMR was also associated with increased risks of all cause mortality (3.21, 1.43 to 7.23), cardiovascular mortality (10.79, 4.09 to 28.42), and major adverse cardiac events (3.23, 2.10 to 4.95). No major heterogeneity was observed for any primary outcomes between recognised myocardial infarction and UMI-ECG or UMI-CMR. The absolute risk differences were 7.50 (95% confidence interval 4.50 to 10.95) per 1000 person years for all cause mortality, 11.04 (5.48 to 18.84) for cardiovascular mortality, and 27.45 (17.1 to 40.05) for major adverse cardiac events in participants with UMI-ECG compared with those without myocardial infarction. The corresponding data for UMI-CMR were 32.49 (6.32 to 91.58), 37.2 (11.7 to 104.20), and 51.96 (25.63 to 92.04), respectively.
Conclusions
UMI-ECG or UMI-CMR is associated with an adverse long term prognosis similar to that of recognised myocardial infarction. Screening for unrecognised myocardial infarction could be useful for risk stratification among patients with a high risk of cardiovascular disease.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

BMJ: 06 May 2020; 369:m1184
Yang Y, Li W, Zhu H, Pan XF, ... Cai X, Huang Y
BMJ: 06 May 2020; 369:m1184 | PMID: 32381490
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Abstract

Higher Activation of the Rostromedial Prefrontal Cortex during Mental Stress Predicts Major Cardiovascular Disease Events in Individuals with Coronary Artery Disease.

Moazzami K, Wittbrodt MT, Lima BB, Nye JA, ... Vaccarino V, Shah AJ

Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease (CAD). Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE.Participants with stable CAD underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high resolution-positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 (IL-6) levels 90 minutes post-stress, and high-frequency heart rate variability (HF-HRV) during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization and heart failure hospitalization.We studied 148 subjects (69% male) with mean ± SD age of 62 ± 8 years. After adjustment for baseline demographics, risk factors, and baseline levels of IL-6 and HF-HRV, higher rmPFC stress reactivity was independently associated with higher IL-6 and lower HF-HRV with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each 1SD increase in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (HR 1.21, 95% CI 1.08-1.37). Stress-induced IL-6 and HF-HRV explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (p=0.03).Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.



Circulation: 10 Jun 2020; epub ahead of print
Moazzami K, Wittbrodt MT, Lima BB, Nye JA, ... Vaccarino V, Shah AJ
Circulation: 10 Jun 2020; epub ahead of print | PMID: 32522022
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Abstract

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Boardman H, Lamata P, Lazdam M, Verburg A, ... Lewandowski AJ, Leeson P

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m; =0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; =0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; =0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m; =0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; =0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; =0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm; =0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (<0.01, =0.01, and =0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.



Hypertension: 19 Apr 2020:HYPERTENSIONAHA11914530; epub ahead of print
Boardman H, Lamata P, Lazdam M, Verburg A, ... Lewandowski AJ, Leeson P
Hypertension: 19 Apr 2020:HYPERTENSIONAHA11914530; epub ahead of print | PMID: 32306767
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Abstract

A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial.

Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC
Aim
We tested the hypothesis that dapagliflozin may regress left ventricular hypertrophy (LVH) in people with type 2 diabetes (T2D).
Methods and results
We randomly assigned 66 people (mean age 67 ± 7 years, 38 males) with T2D, LVH, and controlled blood pressure (BP) to receive dapagliflozin 10 mg once daily or placebo for 12 months. Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging. In the intention-to-treat analysis, dapagliflozin significantly reduced LVM compared with placebo with an absolute mean change of -2.82g [95% confidence interval (CI): -5.13 to -0.51, P = 0.018]. Additional sensitivity analysis adjusting for baseline LVM, baseline BP, weight, and systolic BP change showed the LVM change to remain statistically significant (mean change -2.92g; 95% CI: -5.45 to -0.38, P = 0.025). Dapagliflozin significantly reduced pre-specified secondary endpoints including ambulatory 24-h systolic BP (P = 0.012), nocturnal systolic BP (P = 0.017), body weight (P < 0.001), visceral adipose tissue (VAT) (P < 0.001), subcutaneous adipose tissue (SCAT) (P = 0.001), insulin resistance, Homeostatic Model Assessment of Insulin Resistance (P = 0.017), and high-sensitivity C-reactive protein (hsCRP) (P = 0.049).
Conclusion
Dapagliflozin treatment significantly reduced LVM in people with T2D and LVH. This reduction in LVM was accompanied by reductions in systolic BP, body weight, visceral and SCAT, insulin resistance, and hsCRP. The regression of LVM suggests dapagliflozin can initiate reverse remodelling and changes in left ventricular structure that may partly contribute to the cardio-protective effects of dapagliflozin.
Clinicaltrials.gov identifier
NCT02956811.

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

Eur Heart J: 23 Jun 2020; epub ahead of print
Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC
Eur Heart J: 23 Jun 2020; epub ahead of print | PMID: 32578850
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Abstract

Safety of Transesophageal Echocardiography to Guide Structural Cardiac Interventions.

Freitas-Ferraz AB, Bernier M, Vaillancourt R, Ugalde PA, ... Beaudoin J, Rodés-Cabau J
Background
Despite the widespread use of transesophageal echocardiography (TEE) to guide structural cardiac interventions, studies evaluating safety in this context are lacking.
Objectives
This study sought to determine the incidence, types of complications, and factors associated with esophageal or gastric lesions following TEE manipulation during structural cardiac interventions.
Methods
This was a prospective study including 50 patients undergoing structural cardiac interventions in which TEE played a central role in guiding the procedure (mitral and tricuspid valve repair, left atrial appendage closure, and paravalvular leak closure). An esophagogastroduodenoscopy (EGD) was performed before and immediately after the procedure to look for new injuries that might have arisen during the course of the intervention. Patients were divided in 2 cohorts according to the type of injury: complex lesions (intramural hematoma, mucosal laceration) and minor lesions (petechiae, ecchymosis). The factors associated with an increased risk of complications were assessed.
Results
Post-procedural EGD showed a new injury in 86% (n = 43 of 50) of patients, with complex lesions accounting for 40% (n = 20 of 50) of cases. Patients with complex lesions presented more frequently with an abnormal baseline EGD (70% vs. 37%; p = 0.04) and had a higher incidence of post-procedural dysphagia or odynophagia (40% vs. 10%; p = 0.02). Independent factors associated with an increased risk of complex lesions were a longer procedural time under TEE manipulation (for each 10-min increment in imaging time, odds ratio: 1.27; 95% confidence interval: 1.01 to 1.59) and poor or suboptimal image quality (odds ratio: 4.93; 95% confidence interval: 1.10 to 22.02).
Conclusions
Most patients undergoing structural cardiac interventions showed some form of injury associated with TEE, with longer procedural time and poor or suboptimal image quality determining an increased risk. Imaging experts performing this technique should be aware of the nature of potential complications, to take the necessary precautions to prevent their occurrence and facilitate early diagnosis and treatment.

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

J Am Coll Cardiol: 29 Jun 2020; 75:3164-3173
Freitas-Ferraz AB, Bernier M, Vaillancourt R, Ugalde PA, ... Beaudoin J, Rodés-Cabau J
J Am Coll Cardiol: 29 Jun 2020; 75:3164-3173 | PMID: 32586591
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Abstract

Duration of Pre-Operative Antibiotic Treatment and Culture Results in Patients With Infective Endocarditis.

Gisler V, Dürr S, Irincheeva I, Limacher A, ... Englberger L, Sendi P
Background
Bacterial growth in cultures of resected heart valves of patients with infective endocarditis (IE) is influenced by pre-operative antibiotic treatment (preop-AT).
Objectives
This study sought to evaluate the time dependency of valve culture results (positive valve culture [PVC] vs. negative valve culture) on preop-AT.
Methods
A total of 352 IE episodes in 344 adult patients of our tertiary referral hospital were retrospectively investigated (2005 to 2016). The primary endpoint was PVC results. The study used a logistic additive model adjusted for bacterial species, the McCabe-Jackson classification, and the existence of foreign valve material as covariables.
Results
The 231 included IE cases (187 [81%] men, median age 62 years, 153 [66%] native valves) comprised 58 (25%) PVC results and 173 (75%) negative valve culture results. A multivariable analysis adjusted for bacterial species, McCabe-Jackson classification, and valve type resulted in odds ratios for PVC of 6.35 (95% confidence interval [CI]: 1.94 to 20.78; p = 0.002) and 3.93 (95% CI: 1.57 to 9.84; p = 0.003) for Enterococcus spp. and Staphylococcus spp., respectively. Model-based odds ratios for PVC risk reduction in 2-day intervals of preop-AT ranged from 0.64 (95% CI: 0.61 to 0.68) at day 7 to 0.74 (95% CI: 0.70 to 0.78) at day 13 and 0.98 (95% CI: 0.93 to 1.02) at day 21.
Conclusions
In IE cases treated with valve surgery, Staphylococcus aureus and Enterococcus spp. were associated with valve culture growth. After 7 days of antibiotic treatment, the additional effect of preop-AT on valve culture results per 2-day interval was minor. Antibiotic treatment beyond 21 days had no influence on culture results.

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

J Am Coll Cardiol: 06 Jul 2020; 76:31-40
Gisler V, Dürr S, Irincheeva I, Limacher A, ... Englberger L, Sendi P
J Am Coll Cardiol: 06 Jul 2020; 76:31-40 | PMID: 32616160
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Abstract

Prevalence of Infective Endocarditis in Streptococcal Bloodstream Infections is Dependent on Streptococcal Species.

Chamat S, Dahl A, Østergaard LKM, Arpi M, ... Torp-Pedersen C, Bruun NE

Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs.We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE and cardiac device.Among 6,506 cases with streptococcal BSIs (mean age 68.1 years (SD 16.2), 52.8% men) the IE prevalence was 7.1% (95% CI: 6.5-7.8%). The lowest IE prevalence was found with1.2% (0.8-1.6%) and1.9% (0.9-3.3%). An intermediary IE prevalence was found with4.8% (3.0-7.3%),5.8% (2.9-10.1%) and9.1% (6.6-12.1%). The highest IE prevalence was found with19.4% (15.6-23.5%),(formerly ) 30.2% (24.3-36.7%),34.6% (26.6-43.3%),44.2% (34.0-54.8%) and47.9% (33.3-62.8%). In multivariable analysis usingas reference, all species exceptwere associated with significantly higher IE risk, with the highest risk found withOR 31.0 (18.8-51.1),OR 31.6 (19.8-50.5),OR 59.1 (32.6-107),OR 80.8 (43.9-149) andOR 81.3 (37.6-176).The prevalence of IE in streptococcal BSI is species dependent with , , ,andhaving the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.



Circulation: 24 Jun 2020; epub ahead of print
Chamat S, Dahl A, Østergaard LKM, Arpi M, ... Torp-Pedersen C, Bruun NE
Circulation: 24 Jun 2020; epub ahead of print | PMID: 32580572
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Abstract

A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes.

Nguyen NUN, Canseco DC, Xiao F, Nakada Y, ... Rothermel BA, Sadek HA

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.



Nature: 21 Apr 2020; epub ahead of print
Nguyen NUN, Canseco DC, Xiao F, Nakada Y, ... Rothermel BA, Sadek HA
Nature: 21 Apr 2020; epub ahead of print | PMID: 32499640
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Abstract

Gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration.

Li Y, Feng J, Song S, Li H, ... Hu S, Nie Y

A key cause of cardiovascular diseases\' high mortality is the cardiomyocyte inability to renew after cardiac injury. As a promising strategy to supplement functional myocytes for cardiac repair, there is a pressing need to understand the cellular and molecular mechanisms of heart regeneration.Seven genetic mouse lines were used: global Oncostatin M (OSM) knockout, monocyte-/macrophage-specific OSM deletion, cardiomyocyte-specific lines, including OSMR deletion, gp130 deletion, gp130 activation, and Yap ablation with gp130 activation mice. A series of molecular signaling experiments, including RNA-Seq, immunostaining, co-immunoprecipitation, and Imaging Flow Cytometry, were conducted. Two models of cardiac injury, apical resection and myocardial infarction operation, were performed in neonatal, juvenile, and adult mice. Heart regeneration and cardiac function were evaluated by Masson\'s staining and echocardiography, respectively. Gene recombinant AAV9 was constructed and infected myocardial infarcted mice as a gene therapy.OSM was identified by RNA-Seq as a key upstream regulator of cardiomyocyte proliferation during neonatal heart regeneration in mice. Cardiomyocyte proliferation and heart regeneration was suspended in neonatal mice after cardiac injury when OSM was conditionally knockout in macrophages. The cardiomyocyte-specific deficiency of the OSM receptor heterodimers, OSMR and gp130, individually in cardiomyocytes reduced myocyte proliferation and neonatal heart regeneration. Conditional activation of gp130 in cardiomyocytes promoted cardiomyocyte proliferation and heart regeneration in juvenile and adult mice. Employing RNA-Seq and functional screening, we found that Src mediated gp130-triggered cardiomyocyte proliferation by activating Yap with Y357 phosphorylation independently of Hippo pathway. Cardiomyocyte-specific deletion of Yap inmice blocked the effect of gp130 activation-induced heart regeneration in juvenile mice. Gene therapy with AAV9 encoding constitutively activated gp130 promoted cardiomyocyte proliferation and heart regeneration in adult mice after myocardial infarction.Macrophage recruitment is essential for heart regenerationsecretion of OSM which promotes cardiomyocyte proliferation. As the co-receptor of OSM, gp130 activation is sufficient to promote cardiomyocyte proliferation by activating Yap via Src during heart regeneration. Gp130 is a potential therapeutic target to improve heart regeneration after cardiac injury.



Circulation: 29 Jun 2020; epub ahead of print
Li Y, Feng J, Song S, Li H, ... Hu S, Nie Y
Circulation: 29 Jun 2020; epub ahead of print | PMID: 32600062
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Abstract

Calcineurin Aβ-Specific Anchoring Confers Isoform-Specific Compartmentation and Function in Pathological Cardiac Myocyte Hypertrophy.

Li X, Li J, Martinez EC, Froese A, ... Nikolaev VO, Kapiloff MS

The Ca/calmodulin-dependent phosphatase calcineurin is a key regulator of cardiac myocyte hypertrophy in disease. An unexplained paradox is how the Aβ isoform of calcineurin (CaNAβ) is required for induction of pathological myocyte hypertrophy, despite calcineurin Aα expression in the same cells. In addition, it is unclear how the pleiotropic second messenger Ca drives excitation-contraction coupling, while not stimulating hypertrophy via calcineurin in the normal heart. Elucidation of the mechanisms conferring this selectively in calcineurin signaling should reveal new strategies for targeting the phosphatase in disease.Primary adult rat ventricular myocytes were studied for morphology and intracellular signaling. New Forster Resonance Energy Transfer (FRET) reporters were used to assay Ca and calcineurin activity in living cells. Conditional gene deletion and adeno-associated virus (AAV)-mediated gene delivery in the mouse were used to study calcineurin signaling following transverse aortic constriction .Cdc42-interacting protein (CIP4/TRIP10) was identified as a new polyproline domain-dependent scaffold for CaNAβ2 by yeast-2-hybrid screen. Cardiac myocyte-specific CIP4 gene deletion in mice attenuated pressure overload-induced pathological cardiac remodeling and heart failure. Accordingly, blockade of CaNAβ polyproline-dependent anchoring using a competing peptide inhibited concentric hypertrophy in cultured myocytes, while disruption of anchoringusing an AAV gene therapy vector inhibited cardiac hypertrophy and improved systolic function after pressure overload. Live cell FRET biosensor imaging of cultured myocytes revealed that Ca levels and calcineurin activity associated with the CIP4 compartment were increased by neurohormonal stimulation, but minimally by pacing. Conversely, Ca levels and calcineurin activity detected by non-localized FRET sensors were induced by pacing and minimally by neurohormonal stimulation, providing functional evidence for differential intracellular compartmentation of Ca and calcineurin signal transduction.These results support a structural model for Ca and CaNAβ compartmentation in cells based upon an isoform-specific mechanism for calcineurin protein-protein interaction and localization. This mechanism provides an explanation for the specific role of CaNAβ in hypertrophy and its selective activation under conditions of pathologic stress. Disruption of CaNAβ polyproline-dependent anchoring constitutes a rational strategy for therapeutic targeting of CaNAβ-specific signaling responsible for pathological cardiac remodeling in cardiovascular disease deserving of further pre-clinical investigation.



Circulation: 01 Jul 2020; epub ahead of print
Li X, Li J, Martinez EC, Froese A, ... Nikolaev VO, Kapiloff MS
Circulation: 01 Jul 2020; epub ahead of print | PMID: 32611257
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Abstract

Sex as a Biological Variable in Atherosclerosis.

Man JJ, Beckman JA, Jaffe IZ

Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article reviews the available data. Overall, male animals appear to have more inflamed yet smaller plaques compared to female animals. Plaque inflammation is often used as a surrogate end point for plaque vulnerability in animals. The available data support the notion that rather than plaque size, plaque inflammation may be more relevant in assessing sex-specific mechanisms since the findings correlate with the sex difference in ischemic events and mortality and thus may be more reflective of the human condition. Overall, the number of preclinical studies directly comparing plaque inflammation between the sexes is extremely limited relative to the vast literature exploring atherosclerosis mechanisms. Failure to include both sexes and to address age in mechanistic atherosclerosis studies are missed opportunities to uncover underlying sex-specific mechanisms. Understanding the mechanisms driving sex as a biological variable in atherosclerotic disease is critical to future precision medicine strategies to mitigate what is still the leading cause of death of men and women worldwide.



Circ Res: 23 Apr 2020; 126:1297-1319
Man JJ, Beckman JA, Jaffe IZ
Circ Res: 23 Apr 2020; 126:1297-1319 | PMID: 32324497
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Abstract

Mid- to Late-Life Time-Averaged Cumulative Blood Pressure and Late-Life Cardiac Structure, Function, and Heart Failure.

Teramoto K, Nadruz Junior W, Matsushita K, Claggett B, ... Cheng S, Shah AM

Limited data exist regarding systolic blood pressure (SBP) through mid- to late-life and late-life cardiac function and heart failure (HF) risk. Among 4578 HF-free participants in the ARIC study (Atherosclerosis Risk in Communities) attending the fifth visit (2011-2013; age 75±5 years), time-averaged cumulative SBP was calculated as the sum of averaged SBPs from adjacent consecutive visits (visits 1-5) indexed to total observation time (24±1 years). Calculations were performed using measured SBPs and also incorporating antihypertensive medication specific effect constants (underlying SBP). Outcomes included comprehensive echocardiography at visit 5 and post-visit 5 incident HF, HF with preserved ejection fraction, and reduced ejection fraction. Higher cumulative SBP was associated with greater left ventricular mass and worse diastolic measures (all <0.001), associations that were stronger with underlying compared with cumulative SBP (all <0.05). At 5.6±1.2 years follow-up post-visit 5, higher cumulative measured and underlying SBP were associated with incident HF (hazard ratio per 10 mm Hg for measured: 1.12 [1.01-1.24]; underlying: 1.19 [95% CI, 1.10-1.30]) and HF with preserved ejection fraction (measured: 1.15 [1.00-1.33]; underlying: 1.28 [1.14-1.45]), but not HF with reduced ejection fraction (measured: 1.11 [0.94-1.32]; underlying: 1.11 [0.96-1.24]). Associations with HF and HF with preserved ejection fraction were more robust with cumulative underlying compared with measured SBP (all <0.05). Time-averaged cumulative SBP in mid to late life is associated with worse cardiac function and risk of incident HF, especially HF with preserved ejection fraction, in late life. These associations were stronger considering underlying as opposed to measured SBP, highlighting the importance of prevention and effective treatment of hypertension to prevent late-life cardiac dysfunction and HF.



Hypertension: 14 Jun 2020:HYPERTENSIONAHA12014833; epub ahead of print
Teramoto K, Nadruz Junior W, Matsushita K, Claggett B, ... Cheng S, Shah AM
Hypertension: 14 Jun 2020:HYPERTENSIONAHA12014833; epub ahead of print | PMID: 32536273
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Abstract

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State.

Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, ... Holtgrave DR, Zucker HA
Importance
Hydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events.
Objective
To describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19.
Design, setting, and participants
Retrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020.
Exposures
Receipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither.
Main outcomes and measures
Primary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation).
Results
Among 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine + azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine + azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine + azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings.
Conclusions and relevance
Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.



JAMA: 10 May 2020; epub ahead of print
Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, ... Holtgrave DR, Zucker HA
JAMA: 10 May 2020; epub ahead of print | PMID: 32392282
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Abstract

Abnormalities in Sodium Current and Calcium Homeostasis as Drivers of Arrhythmogenesis in Hypertrophic Cardiomyopathy.

Coppini R, Santini L, Olivotto I, Ackerman MJ, Cerbai E

Hypertrophic cardiomyopathy (HCM) is a common inherited monogenic disease with a prevalence of 1/500 in the general population, representing an important cause of arrhythmic sudden cardiac death (SCD), heart failure, and atrial fibrillation in the young. HCM is a global condition, diagnosed in more than 50 countries and in all continents, HCM affects people of both sexes and various ethnic and racial origins, with similar clinical course and phenotypic expression. The most unpredictable and devastating consequence of HCM is represented by arrhythmic SCD, most commonly caused by sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Indeed, HCM represents one of the main causes of arrhythmic SCD in the young, with a marked preference for children and adults <30 years. SCD is most prevalent in patients with pediatric onset of HCM but may occur at any age. However, risk is substantially lower after 60 years, suggesting that the potential for ventricular tachyarrhythmias is mitigated by ageing. SCD had been linked originally to sports and vigorous activity in HCM patients. However, it is increasingly clear that the majority of events occur at rest or during routine daily occupations, suggesting that triggers are far from consistent. In general, the pathophysiology of SCD in HCM remains unresolved. While the pathologic and physiologic substrates abound and have been described in detail, specific factors precipitating ventricular tachyarrhythmias are still unknown. SCD is a rare phenomenon in HCM cohorts (<1%/year) and attempts to identify patients at risk, while generating clinically useful algorithms for primary prevention, remain very inaccurate on an individual basis. One of the reasons for our limited understanding of these phenomena is that limited translational research exists in the field, while most efforts have focused on clinical markers of risk derived from pathology, instrumental patient evaluation and imaging. Specifically, few studies conducted in animal models and human samples have focused on targeting the cellular mechanisms of arrhythmogenesis in HCM, despite potential implications for therapeutic innovation and SCD prevention. These studies found that altered intracellular Ca2+ homeostasis and increased late Na+ current, leading to an increased likelihood of early and delayed after-depolarizations, contribute to generate arrhythmic events in diseased cardiomyocytes. As an array of novel experimental opportunities have emerged to investigate these mechanisms, including novel \"disease-in-the-dish\" cellular models with patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), important gaps in knowledge remain. Accordingly, the aim of the present review is to provide a contemporary reappraisal of the cellular basis of SCD-predisposing arrhythmias in patients with HCM and discuss the implications for risk stratification and management.

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

Cardiovasc Res: 03 May 2020; epub ahead of print
Coppini R, Santini L, Olivotto I, Ackerman MJ, Cerbai E
Cardiovasc Res: 03 May 2020; epub ahead of print | PMID: 32365196
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Abstract

Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does not Alter Ventricular Function.

Zhang J, Vincent KP, Peter AK, Klos M, ... Knowlton KU, Ross RS

Zonula occludens-1 (ZO-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown.To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function.We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre, (ZO-1cKO), and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO vs control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1 associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CMs in a presumed compensatory manner, but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO vs. CTL.ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.



Circ Res: 28 Apr 2020; epub ahead of print
Zhang J, Vincent KP, Peter AK, Klos M, ... Knowlton KU, Ross RS
Circ Res: 28 Apr 2020; epub ahead of print | PMID: 32345129
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Abstract

Comprehensive review of evaluation and management of cardiac paragangliomas.

Tella SH, Jha A, Taïeb D, Horvath KA, Pacak K

Cardiac paraganglioma (PGL) is a rare neuroendocrine tumour causing significant morbidity primarily due to norepinephrine secretion potentially causing severe hypertension, palpitations, lethal tachyarrhythmias, stroke and syncope. Cardiologists are faced with two clinical scenarios. The first is the elevated norepinephrine, whose actions must be properly counteracted by adrenoceptor blockade to avoid catastrophic consequences. The second is to evaluate the precise location of a cardiac PGL and its spread since compression of cardiovascular structures may result in ischaemia, angina, non-noradrenergic-induced arrhythmia, cardiac dysfunction or failure. Thus, appropriate assessment of elevated norepinephrine by its metabolite normetanephrine is a gold biochemical standard at present. Furthermore, dedicated cardiac CT, MRI and transthoracic echocardiogram are necessary for the precise anatomic information of cardiac PGL. Moreover, a cardiologist needs to be aware of advanced functional imaging using Ga-DOTA(0)-Tyr(3)-octreotide positron emission tomography/CT, which offers the best cardiac PGL-specific diagnostic accuracy and helps to stage and rule out metastasis, determining the next therapeutic strategies. Patients should also undergo genetic testing, especially for mutations in genes encoding succinate dehydrogenase enzyme subunits that are most commonly present as a genetic cause of these tumours. Curative surgical resection after appropriate α-adrenoceptor and β-adrenoceptor blockade in norepinephrine-secreting tumours is the primary therapeutic strategy. Therefore, appropriate and up-to-date knowledge about early diagnosis and management of cardiac PGLs is paramount for optimal outcomes in patients where a cardiologist is an essential team member of a multidisciplinary team in its management.

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

Heart: 21 May 2020; epub ahead of print
Tella SH, Jha A, Taïeb D, Horvath KA, Pacak K
Heart: 21 May 2020; epub ahead of print | PMID: 32444502
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Abstract

Obesity Phenotypes, Diabetes, and Cardiovascular Diseases.

Piché ME, Tchernof A, Després JP

This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.



Circ Res: 21 May 2020; 126:1477-1500
Piché ME, Tchernof A, Després JP
Circ Res: 21 May 2020; 126:1477-1500 | PMID: 32437302
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Abstract

Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation.

Kolijn D, Pabel S, Tian Y, Lódi M, ... Sossalla S, Hamdani N
Aims
Sodium-glucose-cotransporter-2 (SGLT2) inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF).
Methods and results
The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1,VCAM-1,TNF-α,IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO-levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an antioxidative/PKGIα-dependent manner. Monovariate linear regression-analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients.
Conclusion
Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO-sGC-cGMP-cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.
Translational perspective
Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have shown beneficial effects in heart failure (HF) patients with and without diabetes. Clinical trials are recruiting HF patients with preserved ejection fraction (HFpEF) to test for SGLT2 inhibitor effects. However, the underlying mechanisms by which these drugs exert their beneficial effects remain elusive. Our study demonstrates that acute empagliflozin in human and rat HFpEF myocardium reduces inflammatory/oxidative stress and improves the NO-sGC-cGMP-cascade and PKGIα activity via reduced PKGIα oxidation. Consequently, leading to improved cardiomyocyte function via PKGIα and its concomitant anti-oxidative effect. This study, therefore, provides mechanistic evidence supporting further clinical investigation of empagliflozin in HFpEF.

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

Cardiovasc Res: 11 May 2020; epub ahead of print
Kolijn D, Pabel S, Tian Y, Lódi M, ... Sossalla S, Hamdani N
Cardiovasc Res: 11 May 2020; epub ahead of print | PMID: 32396609
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Abstract

Early cardiac magnetic resonance imaging in troponin-positive acute chest pain and non-obstructed coronary arteries.

Vágó H, Szabó L, Dohy Z, Czimbalmos C, ... Becker D, Merkely B
Objective
We assessed the diagnostic and prognostic implications of early cardiac magnetic resonance (CMR), CMR-based deformation imaging and conventional risk factors in patients with troponin-positive acute chest pain and non-obstructed coronary arteries.
Methods
In total, 255 patients presenting between 2009 and 2019 with troponin-positive acute chest pain and non-obstructed coronary arteries who underwent CMR in ≤7 days were followed for a clinical endpoint of all-cause mortality. Cine movies, T2-weighted and late gadolinium-enhanced images were evaluated to establish a diagnosis of the underlying heart disease. Further CMR analysis, including left ventricular strain, was carried out.
Results
CMR (performed at a mean of 2.7 days) provided the diagnosis in 86% of patients (54% myocarditis, 22% myocardial infarction (MI) and 10% Takotsubo syndrome and myocardial contusion (n=1)). The 4-year mortality for a diagnosis of MI, myocarditis, Takotsubo and normal CMR patients was 10.2%, 1.6%, 27.3% and 0%, respectively. We found a strong association between CMR diagnosis and mortality (log-rank: 24, p<0.0001). Takotsubo and MI as the diagnosis, age, hypertension, diabetes, female sex, ejection fraction, stroke volume index and most of the investigated strain parameters were univariate predictors of mortality; however, in the multivariate analysis, only hypertension and circumferential mechanical dispersion measured by strain analysis were independent predictors of mortality.
Conclusions
CMR performed in the early phase establishes the proper diagnosis in patients with troponin-positive acute chest pain and non-obstructed coronary arteries and provides additional prognostic factors. This may indicate that CMR could play an additional role in risk stratification in this patient population.

© 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: 22 May 2020; epub ahead of print
Vágó H, Szabó L, Dohy Z, Czimbalmos C, ... Becker D, Merkely B
Heart: 22 May 2020; epub ahead of print | PMID: 32447308
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Abstract

Altered Atrial Cytosolic Calcium Handling Contributes to the Development of Postoperative Atrial Fibrillation.

Fakuade FE, Steckmeister V, Seibertz F, Gronwald J, ... Mason FE, Voigt N
Aims
Atrial fibrillation is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation-contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF.
Methods and results
Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (AP, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaT) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved NCX function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modeling indicated that reduced SERCA activity promotes occurrence of CaT- and AP-alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25-8 Hz).
Conclusions
Biochemical, functional and modeling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.
Translational perspective
Development of atrial fibrillation (AF) within the immediate postoperative period (poAF), represents one of the most frequent complications after cardiac surgery and is associated with poorer outcomes. Our results suggest that reduced Ca2+ uptake into the sarcoplasmic reticulum (SR), associated with increased cellular susceptibility to Ca2+-transient (CaT)- and action potential (AP)-alternans, contributes to the arrhythmogenic substrate predisposing patients to the development of poAF. Therefore, modulation of SERCA activity may represent a novel mechanistic target to prevent development of poAF.Furthermore, we show that the impaired SR Ca2+ uptake contributes to reduced systolic Ca2+ release and impaired atrial contractility in poAF patients. Atrial contractility may therefore represent an important factor for identification of patients at risk for poAF development.

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

Cardiovasc Res: 09 Jun 2020; epub ahead of print
Fakuade FE, Steckmeister V, Seibertz F, Gronwald J, ... Mason FE, Voigt N
Cardiovasc Res: 09 Jun 2020; epub ahead of print | PMID: 32520995
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Abstract

Positron emission tomography imaging in cardiovascular disease.

Tarkin JM, Ćorović A, Wall C, Gopalan D, Rudd JH

Positron emission tomography (PET) imaging is useful in cardiovascular disease across several areas, from assessment of myocardial perfusion and viability, to highlighting atherosclerotic plaque activity and measuring the extent of cardiac innervation in heart failure. Other important roles of PET have emerged in prosthetic valve endocarditis, implanted device infection, infiltrative cardiomyopathies, aortic stenosis and cardio-oncology. Advances in scanner technology, including hybrid PET/MRI and total body PET imaging, as well as the development of novel PET tracers and cardiac-specific postprocessing techniques using artificial intelligence will undoubtedly continue to progress the field.

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

Heart: 21 Jun 2020; epub ahead of print
Tarkin JM, Ćorović A, Wall C, Gopalan D, Rudd JH
Heart: 21 Jun 2020; epub ahead of print | PMID: 32571959
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Abstract

Advanced imaging of right ventricular anatomy and function.

Badano LP, Addetia K, Pontone G, Torlasco C, ... Parati G, Muraru D

Right ventricular (RV) size and function are important predictors of cardiovascular morbidity and mortality in patients with various conditions. However, non-invasive assessment of the RV is a challenging task due to its complex anatomy and location in the chest. Although conventional echocardiography is widely used, its limitations in RV assessment are well recognised. New techniques such as three-dimensional and speckle tracking echocardiography have overcome the limitations of conventional echocardiography allowing a comprehensive, quantitative assessment of RV geometry and function without geometric assumptions. Cardiac magnetic resonance (CMR) and CT provide accurate assessment of RV geometry and function, too. In addition, tissue characterisation imaging for myocardial scar and fat using CMR and CT provides important information regarding the RV that has clinical applications for diagnosis and prognosis in a broad range of cardiac conditions. Limitations also exist for these two advanced modalities including availability and patient suitability for CMR and need for contrast and radiation exposure for CT. Hybrid imaging, which is able to integrate anatomical information (usually obtained by CT or CMR) with physiological and molecular data (usually obtained with positron emission tomography), can provide optimal in vivo evaluation of Rv functional impairment. This review summarises the clinically useful applications of advanced echocardiography techniques, CMR and CT for comprehensive assessment of RV size, function and mechanics.

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

Heart: 02 Jul 2020; epub ahead of print
Badano LP, Addetia K, Pontone G, Torlasco C, ... Parati G, Muraru D
Heart: 02 Jul 2020; epub ahead of print | PMID: 32620556
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Abstract

Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review.

Gertz MA, Dispenzieri A
Importance
Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis and 25% of patients with amyloid transthyretin (ATTR) amyloidosis die within 24 months of diagnosis. Effective therapy exists but is ineffective if end-organ damage is severe.
Objective
To provide evidence-based recommendations that could allow clinicians to diagnose this rare set of diseases earlier and enable accurate staging and counseling about prognosis.
Evidence review
A comprehensive literature search was conducted by a reference librarian with publication dates from January 1, 2000, to December 31, 2019. Key search terms included amyloid, amyloidosis, nephrotic syndrome, heart failure preserved ejection fraction, and peripheral neuropathy. Exclusion criteria included case reports, non-English-language text, and case series of fewer than 10 patients. The authors independently selected and appraised relevant literature.
Findings
There was a total of 1769 studies in the final data set. Eighty-one articles were included in this review, of which 12 were randomized clinical trials of therapy that included 3074 patients, 9 were case series, and 3 were cohort studies. The incidence of AL amyloidosis is approximately 12 cases per million persons per year and there is an estimated prevalence of 30 000 to 45 000 cases in the US and European Union. The incidence of variant ATTR amyloidosis is estimated to be 0.3 cases per year per million persons with a prevalence estimate of 5.2 cases per million persons. Wild-type ATTR is estimated to have a prevalence of 155 to 191 cases per million persons. Amyloidosis should be considered in the differential diagnosis of adult nondiabetic nephrotic syndrome; heart failure with preserved ejection fraction, particularly if restrictive features are present; unexplained hepatomegaly without imaging abnormalities; peripheral neuropathy with distal sensory symptoms, such as numbness, paresthesia, and dysesthesias (although the autonomic manifestations occasionally may be the presenting feature); and monoclonal gammopathy of undetermined significance with atypical clinical features. Staging can be performed using blood testing only. Therapeutic decision-making for AL amyloidosis involves choosing between high-dose chemotherapy and stem cell transplant or bortezomib-based chemotherapy. There are 3 therapies approved by the US Food and Drug Administration for managing ATTR amyloidosis, depending on clinical phenotype.
Conclusions and relevance
All forms of amyloidosis are underdiagnosed. All forms now have approved therapies that have been demonstrated to improve either survival or disability and quality of life. The diagnosis should be considered in patients that have a multisystem disorder involving the heart, kidney, liver, or nervous system.



JAMA: 06 Jul 2020; 324:79-89
Gertz MA, Dispenzieri A
JAMA: 06 Jul 2020; 324:79-89 | PMID: 32633805
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Abstract

The Trouble with Group 3 Pulmonary Hypertension in Interstitial Lung Disease: Dilemmas in Diagnosis and the Conundrum of Treatment.

King CS, Shlobin OA

Pulmonary hypertension due to interstitial lung disease (PH-ILD) can complicate a multitude of interstitial lung diseases including idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, and non-specific interstitial pneumonitis. Development of PH-ILD is associated with increased need for supplemental oxygen, reduced mobility, and decreased survival. A high index of suspicion is required to make the diagnosis given the substantial overlap in symptoms with those of interstitial lung disease without PH. Severely reduced diffusing capacity or six-minute walk test distance, prominent exertional desaturation and impaired heart rate recovery following exercise are all suggestive of the development of PH-ILD. Traditional transthoracic echocardiography (TTE) is the most commonly employed screening test for PH-ILD but it lacks sensitivity and specificity. Newer echocardiograpahic tools employing 3D assessment of the right ventricle may have a role in both prognosis and monitoring of patients with PH-ILD. Right heart catheterization remains the gold standard for confirming a diagnosis of PH-ILD. While there is little debate over the use of supplemental oxygen and diuretic therapy in the treatment of PH-ILD, treatment with pulmonary vasodilator therapy remains controversial. Although several studies have been terminated prematurely for harm, the recently completed INCREASE trial of inhaled treprostinil appears to validate the concept of treatment of PH-ILD with pulmonary vasodilators and hopefully will serve as a foundation from which future studies can be developed.

Copyright © 2020. Published by Elsevier Inc.

Chest: 05 May 2020; epub ahead of print
King CS, Shlobin OA
Chest: 05 May 2020; epub ahead of print | PMID: 32387520
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Abstract

Obstructive sleep apnoea syndrome and left ventricular hypertrophy: a meta-analysis of echocardiographic studies.

Cuspidi C, Tadic M, Sala C, Gherbesi E, Grassi G, Mancia G
Aim
We investigated the association between obstructive sleep apnoea (OSA) and subclinical cardiac organ damage through a meta-analysis of echocardiographic studies that provided data on left ventricular hypertrophy (LVH), assessed as a categorical or continuous variable.
Design
The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from 1 January 2000 to 15 August 2019. Studies were detected by using the following terms: \'obstructive sleep apnea\', \'sleep quality\', \'sleep disordered breathing\', \'cardiac damage\', \'left ventricular mass\', \'left ventricular hypertrophy\', and \'echocardiography\'.
Results
Meta-analysis included 5550 patients with OSA and 2329 non-OSA controls from 39 studies. The prevalence of LVH in the pooled OSA population was 45% (CI 35--55%). Meta-analysis of studies comparing the prevalence of LVH in participants with OSA and controls showed that OSA was associated with an increased risk of LVH (OR = 1.70, CI 1.44-2.00, P < 0.001). LV mass was significantly increased in patients with severe OSA as compared with controls (SMD 0.46 ± 0.08, CI 0.29-0.62, P < 0.001) or with mild OSA. This was not the case for studies comparing patients with unselected or predominantly mild OSA and controls (0.33 ± 0.17, CI -0.01 to 0.67, P = 0.057).
Conclusion
The present meta-analysis expands previous information on the relationship between OSA and echocardiographic LVH, so far based on individual studies. The overall evidence strongly suggests that the likelihood of LVH increases with the severity of OSA, thus exhibiting a continuous relationship.



J Hypertens: 03 May 2020; epub ahead of print
Cuspidi C, Tadic M, Sala C, Gherbesi E, Grassi G, Mancia G
J Hypertens: 03 May 2020; epub ahead of print | PMID: 32371766
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Abstract

COVID-19 and Decompressive Hemicraniectomy for Acute Ischemic Stroke.

Liang JW, Reynolds AS, Reilly K, Lay C, ... Dangayach NS,
Background and purpose
Young patients with malignant cerebral edema have been shown to benefit from early decompressive hemicraniectomy. The impact of concomitant infection with coronavirus disease 2019 (COVID-19) and how this should weigh in on the decision for surgery is unclear.
Methods
We retrospectively reviewed all COVID-19-positive patients admitted to the neuroscience intensive care unit for malignant edema monitoring. Patients with >50% of middle cerebral artery involvement on computed tomography imaging were considered at risk for malignant edema.
Results
Seven patients were admitted for monitoring of whom 4 died. Cause of death was related to COVID-19 complications, and these were either seen both very early and several days into the intensive care unit course after the typical window of malignant cerebral swelling. Three cases underwent surgery, and 1 patient died postoperatively from cardiac failure. A good outcome was attained in the other 2 cases.
Conclusions
COVID-19-positive patients with large hemispheric stroke can have a good outcome with decompressive hemicraniectomy. A positive test for COVID-19 should not be used in isolation to exclude patients from a potentially lifesaving procedure.



Stroke: 07 Jul 2020:STROKEAHA120030804; epub ahead of print
Liang JW, Reynolds AS, Reilly K, Lay C, ... Dangayach NS,
Stroke: 07 Jul 2020:STROKEAHA120030804; epub ahead of print | PMID: 32639861
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Abstract

Performance and Interpretation of Invasive Hemodynamic Exercise Testing.

Jain CC, Borlaug BA

Exertional dyspnea is a common complaint for patients seen in pulmonary, cardiac and general medicine clinics, and elucidating the cause is often challenging, particularly when physical examination, echocardiography, radiography and pulmonary function test results are inconclusive. Invasive cardiopulmonary exercise testing (CPET) has emerged as the gold standard test to define causes of dyspnea and exertional limitation in this population. In this review, we describe the methods for performing and interpreting invasive CPET, with particular attention to the hemodynamic and blood sampling data as they apply to patients being evaluated for heart failure and pulmonary hypertension.

Copyright © 2020. Published by Elsevier Inc.

Chest: 27 May 2020; epub ahead of print
Jain CC, Borlaug BA
Chest: 27 May 2020; epub ahead of print | PMID: 32473950
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Abstract

Association between right ventricle dysfunction and poor outcome in patients with septic shock.

Kim JS, Kim YJ, Kim M, Ryoo SM, Kim WY
Objective
Sepsis-induced myocardial dysfunction (SIMD) can involve both the left and right ventricles. However, the characteristics and outcomes across various manifestations of SIMD remain unknown.
Methods
This was a retrospective cohort study using a prospective registry of septic shock from January 2011 and April 2017. Patients with clinically presumed cardiac dysfunction underwent echocardiography within 72 hours after admission and were enrolled (n=778). SIMD was classified as left ventricle (LV) systolic/diastolic and right ventricle (RV) dysfunction, which were defined based on the American Society of Echocardiography criteria. The primary outcome was 28-day mortality.
Results
Of the 778 septic shock patients who underwent echocardiography, 270 (34.7%) showed SIMD. The median age was 67.0 years old, and the male was predominant (57.3%). Among them, 67.3% had LV systolic dysfunction, 40.7% had RV dysfunction and 39.3% had LV diastolic dysfunction. Although serum lactate level and sequential organ failure assessment score were not significantly different between groups, SIMD group showed higher troponin I (0.1 vs 0.1 ng/mL; p=0.02) and poor clinical outcomes, including higher 28-day mortality (35.9 vs 26.8%; p<0.01), longer intensive care unit length of stay (5 vs 2 days; p<0.01) and prolonged mechanical ventilation (9 vs 4 days; p<0.01). Multivariate analysis showed that isolated RV dysfunction was an independent risk factor of 28-day mortality (OR 2.26, 95% CI 1.04 to 4.91).
Conclusions
One-third of patients with septic shock showed various myocardial dysfunctions. LV systolic dysfunction was common; however, only RV dysfunction was associated with short-term mortality.

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

Heart: 07 Jul 2020; epub ahead of print
Kim JS, Kim YJ, Kim M, Ryoo SM, Kim WY
Heart: 07 Jul 2020; epub ahead of print | PMID: 32641318
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Abstract

Maternal myocardial dysfunction after normotensive fetal growth restriction compared with hypertensive pregnancies: a speckle-tracking study.

Orabona R, Mohseni Z, Sciatti E, Mulder EG, ... Ghossein-Doha C, Spaanderman MEA
Objective
Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR.
Methods
For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity.
Results
Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR.
Conclusion
Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.



J Hypertens: 05 Jun 2020; epub ahead of print
Orabona R, Mohseni Z, Sciatti E, Mulder EG, ... Ghossein-Doha C, Spaanderman MEA
J Hypertens: 05 Jun 2020; epub ahead of print | PMID: 32516293
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Abstract

Mechanisms of exercise limitation and prevalence of pulmonary hypertension in pulmonary Langerhans cell histiocytosis.

Heiden GI, Sobral JB, Gonçalves Freitas CS, Pereira de Albuquerque AL, ... Souza R, Baldi BG
Background
Pulmonary Langerhans cell histiocytosis (PLCH) determines reduced exercise capacity. The speculated mechanisms of exercise impairment in PLCH are ventilatory and cardiocirculatory limitations, including pulmonary hypertension (PH).
Research question
What are the mechanisms of exercise limitation, the exercise capacity and the prevalence of dynamic hyperinflation (DH) and PH in PLCH?
Study design and methods
In a cross-sectional study, PLCH patients underwent an incremental treadmill cardiopulmonary exercise test with an evaluation of DH, pulmonary function tests, and transthoracic echocardiography. Those patients with lung diffusing capacity for carbon monoxide (DLCO) less than 40% predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity (TRV) greater than 2.5 m/s and/or with indirect PH signs underwent right heart catheterization.
Results
Thirty-five patients were included (68% women, 47 ± 11 years old). Ventilatory and cardiocirculatory limitations, impairment suggestive of PH, and impaired gas exchange occurred in 88%, 67%, 29%, and 88% of patients, respectively. The limitation was multifactorial in 71%, exercise capacity was reduced in 71%, and DH occurred in 68% of patients. Forced expiratory volume in the first second (FEV) and DLCO were 64 ± 22% predicted and 56 ± 21% predicted, respectively. Reduction in DLCO, an obstructive pattern, and air trapping occurred in 80%, 77%, and 37% of patients, respectively. FEV and DLCO were good predictors of exercise capacity. The prevalence of PH was 41%, predominantly with pre-capillary pattern, and mean pulmonary artery pressure correlated best with FEV and TRV.
Interpretation
PH is frequent and exercise impairment is common and multifactorial in PLCH. The most prevalent mechanisms include ventilatory, cardiocirculatory, and suggestive of PH limitations.

Copyright © 2020. Published by Elsevier Inc.

Chest: 28 Jun 2020; epub ahead of print
Heiden GI, Sobral JB, Gonçalves Freitas CS, Pereira de Albuquerque AL, ... Souza R, Baldi BG
Chest: 28 Jun 2020; epub ahead of print | PMID: 32615192
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Abstract

Evaluation of left ventricular systolic function using synchronized analysis of heart sounds and the electrocardiogram.

Li XC, Liu XH, Liu LB, Li SM, Wang YQ, Mead RH
Background
Heart failure is a major health concern and often requires echocardiography to confirm the diagnosis. We introduce a new method that uses a wearable heart sound and electrocardiogram (ECG) device that can be used in the outpatient setting.
Objective
The purpose of this study was to determine the value of synchronized analysis of heart sounds and ECG in identifying patients with depressed left ventricular ejection fraction (dLVEF) <50%.
Methods
One hundred eighty-nine patients (76 with dLVEF; 113 with normal ejection fraction) were enrolled. All were admitted to the hospital because of dyspnea or chest discomfort. N-Terminal pro-B-type natriuretic peptide (NT-proBNP) was measured in all patients. LVEF was determined by echocardiography. Heart sound and ECG signals were simultaneously recorded using the wearable synchronized phonocardiogram and ECG device. Heart sound and ECG signals were automatically analyzed using wavelet analysis and utilized to determine electromechanical activation time (EMAT), EMAT/RR, S1-S2 time, and S1-S2/RR.
Results
EMAT in the dLVEF group was significantly higher than that in the control group (159.82 ± 83 ms vs 91.58 ± 28 ms). Pearson correlation test showed a negative correlation between EMAT and LVEF (r = -0.449; P <.001). Receiver operating characteristic curve analysis demonstrated that the sensitivity and specificity of EMAT ≥104 ms for the diagnosis of EF <50% were 92.1% and 92%, respectively. Patients with intermediate NT-proBNP values were identified as dLVEF by EMAT ≥104 ms, with sensitivity of 93.5% and specificity of 92.8%.
Conclusion
The heart sound and ECG signal index EMAT contributes to the diagnosis of EF <50% and is especially helpful in patients with an inconclusive NT-proBNP value.

Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Heart Rhythm: 29 Apr 2020; 17:876-880
Li XC, Liu XH, Liu LB, Li SM, Wang YQ, Mead RH
Heart Rhythm: 29 Apr 2020; 17:876-880 | PMID: 32354453
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Abstract

Cardiac magnetic resonance-derived fibrosis, strain and molecular biomarkers of fibrosis in hypertensive heart disease.

Pichler G, Redon J, Martínez F, Solaz E, ... Karth GD, Maceira A
Aims
Myocardial fibrosis is a relevant component of hypertensive heart disease (HHD). Novel cardiovascular magnetic resonance (CMR) imaging techniques have shown potential in quantification of diffuse cardiac fibrosis, with T1 mapping, and estimating preclinical cardiac dysfunction, with strain analysis. Molecular biomarkers of fibrosis have been related with clinical outcomes and histologically proven myocardial fibrosis. The relationship between these CMR-imaging techniques and circulating biomarkers is not fully understood.
Methods and results
CMR was performed on a 3T scanner in 36 individuals with HHD. Extracellular volume fraction (ECV) and the partition coefficient were assessed using the T1 mapping technique shMOLLI. Longitudinal, circumferential and radial strain was assessed using CMR-Feature Tracking. Molecular biomarkers of collagen synthesis (PICP and PIIINP) and collagen degradation (CITP and MMP-1) were measured in blood using commercial kits. Correlation models showed a significant relationship of T1 mapping measures with left atrial diameter, LV mass, LV posterior wall thickness, LV end-diastolic volume and longitudinal strain. In fully adjusted regression models, ECV was associated with left atrial diameter (β=0.75, P = 0.005) and longitudinal strain (β = 0.43, P = 0.030); the partition coefficient was associated with LV posterior wall thickness (β = 0.53, P = 0.046). Strain measures were associated with cardiac geometry, and longitudinal strain was marginally associated with CITP.
Conclusion
In individuals with HHD, CMR-derived measures of myocardial fibrosis and function are related and might be useful tools for the identification and characterization of preclinical cardiac dysfunction and diffuse myocardial fibrosis. Molecular biomarkers of fibrosis were marginally associated with myocardial strain, but not with the extension of CMR-measured cardiac fibrosis.



J Hypertens: 24 Jun 2020; epub ahead of print
Pichler G, Redon J, Martínez F, Solaz E, ... Karth GD, Maceira A
J Hypertens: 24 Jun 2020; epub ahead of print | PMID: 32618887
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Abstract

A speckle tracking echocardiographic study on right ventricular function in primary aldosteronism.

Chen YL, Xu TY, Xu JZ, Zhu LM, Li Y, Wang JG
Objective
We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism.
Methods
Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS).
Results
Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ± 22.6 vs. 95.8 ± 18.5 g/m) and left atrial volume index (26.9 ± 6.0 vs. 24.7 ± 5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E\'t (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P < 0.001) lower RV4CLS (-18.1 ± 2.5 vs. -23.3 ± 3.4%) and RVFWLS (-21.7 ± 3.7 vs. -27.9 ± 4.5%) than primary hypertensive patients. Overall, RV4CLS and RVFWLS were significantly (r = -0.58 to -0.41, P < 0.001) correlated with plasma aldosterone concentration and 24-h urinary aldosterone excretion. After adjustment for confounding factors, the associations for RV4CLS and RVFWLS with 24-h urinary aldosterone excretion remained significant (P < 0.001), with a standardized coefficient of -0.48 and -0.55, respectively.
Conclusion
In addition to left ventricular abnormalities, primary aldosteronism patients also show impaired right ventricular function, probably because of hyperaldosteronism.



J Hypertens: 24 Jun 2020; epub ahead of print
Chen YL, Xu TY, Xu JZ, Zhu LM, Li Y, Wang JG
J Hypertens: 24 Jun 2020; epub ahead of print | PMID: 32618893
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Abstract

Late I blocker GS967 Suppress Polymorphic VT in a Transgenic Rabbit Model of Long QT Type 2.

Hwang J, Kim TY, Terentyev D, Zhong M, ... Koren G, Choi BR

- Long QT syndrome (LQTS) has been associated with sudden cardiac death likely caused by early afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late sodium current (I) may counterbalance the reduced repolarization reserve in LQTS and prevent EADs and PVTs.- We tested the effects of the selective I blocker GS967 on PVT induction in a transgenic rabbit model of LQTS type 2 (LQT2) using intact heart optical mapping, cellular electrophysiology and confocal Ca imaging, and computer modeling.- GS967 reduced (ventricular fibrillation) VF induction under a rapid pacing protocol (n=7/14 hearts in control vs. 1/14 hearts at 100 nM) without altering APD or restitution and dispersion. GS967 suppressed PVT incidences by reducing Ca-mediated EADs and focal activity during isoproterenol perfusion (at 30 nM, n=7/12 and 100 nM n=8/12 hearts without EADs and PVTs). Confocal Ca imaging of LQT2 myocytes revealed that GS967 shortened Ca transient duration via accelerating Na/Ca exchanger (I)-mediated Ca efflux from cytosol, thereby reducing EADs. Computer modeling revealed that I potentiates EADs in the LQT2 setting through 1) providing additional depolarizing currents during AP plateau phase, 2) increasing intracellular Na (Na) that decreases the depolarizing I thereby suppressing the AP plateau and delaying the activation of slowly-activating delayed rectifier K channels (I), suggesting important roles of I in regulating Na.- Selective I blockade by GS967 prevents EADs and abolishes PVT in LQT2 rabbits by counterbalancing the reduced repolarization reserve and normalizing Na.



Circ Arrhythm Electrophysiol: 05 Jul 2020; epub ahead of print
Hwang J, Kim TY, Terentyev D, Zhong M, ... Koren G, Choi BR
Circ Arrhythm Electrophysiol: 05 Jul 2020; epub ahead of print | PMID: 32628505
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Impact:
Abstract

Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management.

Siripanthong B, Nazarian S, Muser D, Deo R, ... Cooper LT, Chahal CAA

Human coronavirus-associated myocarditis is known, and a number of COVID-19-related myocarditis cases have been reported. The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host\'s immune response. COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience. The clinical findings include changes in ECG, cardiac biomarkers, and impaired cardiac function. When cardiac MRI is infeasible, cardiac CT angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns. Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered. Where the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression. Arrhythmias are not uncommon in the COVID-19 patients; however, its pathophysiology is still speculative. Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatments. The long-term impact of COVID-19 myocarditis, including in the majority of mild cases remains unknown.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 04 May 2020; epub ahead of print
Siripanthong B, Nazarian S, Muser D, Deo R, ... Cooper LT, Chahal CAA
Heart Rhythm: 04 May 2020; epub ahead of print | PMID: 32387246
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Abstract

Coronary perivascular epicardial adipose tissue and major adverse cardiovascular events after ST segment-elevation myocardial infarction.

Toya T, Corban MT, Imamura K, Bois JP, ... Lerman LO, Lerman A
Background and aims
Perivascular epicardial adipose tissue (pEAT) plays a key role in the progression of atherosclerosis, plaque rupture, and thrombosis. However, the relationship between pEAT and prognosis after revascularization of ST-segment elevation myocardial infarction (STEMI) is unknown. This study aimed to investigate the relationship between pEAT thickness and prognosis after STEMI.
Methods
We studied 180 STEMI patients (mean age 59.4 ± 13.3 years, 78.9% male) who underwent cardiac magnetic resonance (CMR) imaging within 1 week of prompt infarct-related artery revascularization and 52 age/sex/body mass index-matched controls (mean age 59.9 ± 13.5 years, 78.9% male). pEAT thickness indexed to body surface area at five locations, infarct size, left ventricular ejection fraction (LVEF), and coronary microvascular obstruction (MVO) were evaluated by CMR. Associations between pEAT index and 1-year composite major adverse cardiovascular events (MACE), infarct size, LVEF, and MVO were analyzed.
Results
Mean pEAT indices were significantly higher in STEMI patients than controls. In STEMI patients, higher pEAT indices at the superior and inferior interventricular groove (SIVG and IIVG, respectively) were significantly associated with larger infarct size, higher prevalence of MVO, and inversely correlated with post-infarct LVEF. SIVG pEAT index was an independent predictor of composite MACE in post-STEMI patients with an odds ratio of 2.26 (95% confidence interval 1.63-3.13; p < 0.0001) after adjustment for age, sex, LVEF, and 2.71 (95% confidence interval 1.93-3.80; p < 0.0001) after adjustment for age, sex, previous myocardial infarction, diabetes mellitus, and renal function.
Conclusions
STEMI patients have significantly higher pEAT indices than controls. SIVG pEAT index independently predicts composite MACE in revascularized STEMI patients, underscoring the potentially prognostic value of this variable.

Copyright © 2020. Published by Elsevier B.V.

Atherosclerosis: 28 Apr 2020; 302:27-35
Toya T, Corban MT, Imamura K, Bois JP, ... Lerman LO, Lerman A
Atherosclerosis: 28 Apr 2020; 302:27-35 | PMID: 32417697
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Abstract

A novel nine-partition method using fluoroscopic images for guiding left bundle branch pacing.

Jiang H, Hou X, Qian Z, Wang Y, ... Li K, Zou J
Background
Left bundle branch (LBB) pacing is a novel pacing modality but there is no standard fluoroscopic methodology.
Objective
This study aimed to analyze the characteristics of His bundle (HB) and LBB pacing lead locations and establish a method to guide LBB pacing using fluoroscopic images.
Methods
Seventy patients who underwent HB or LBB pacing were enrolled. The fluoroscopic image was recorded and ventricular contraction ring in the RAO 30° projection was determined. The region between the apex and ventricular contraction ring was divided into nine partitions. All patients underwent postoperative CT scan to confirm components of ventricular contraction ring and to measure the distance from lead tip to junction of non-coronary and right coronary cusp (Tip-NCC).
Results
HB and LBB pacing leads were successfully implanted in 11 and 35 patients, respectively. All HB pacing leads were distributed in the second partition, and 94.2% of LBB pacing leads were in the junctional area of second and fifth partitions. CT image confirmed that ventricular contraction ring was composed of cardiac valves. The Tip-NCC distance of LBB and HB pacing leads were 3.8 ± 0.6 cm and 1.9 ± 0.2 cm. Under the guidance of the nine-partition method, the success rate of LBB pacing in 30 prospective patients increased from 58.3% to 83.3% (p = 0.03). The fluoroscopic time and number of screwing sites also significantly decreased.
Conclusion
The distributions of HB and LBB pacing leads exhibited unique imaging characteristics. A new nine-partition method is useful to guide successful LBB pacing.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 13 May 2020; epub ahead of print
Jiang H, Hou X, Qian Z, Wang Y, ... Li K, Zou J
Heart Rhythm: 13 May 2020; epub ahead of print | PMID: 32417259
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Abstract

Clinical impact of left ventricular paced conduction disturbance in cardiac resynchronization therapy.

Ueda N, Noda T, Nakajima I, Ishibashi K, ... Yasuda S, Kusano K
Background
Myocardial scarring is associated with non-response to cardiac resynchronization therapy (CRT) and conduction delay. Little is known about the significance and cause of left ventricular (LV) paced conduction disturbance (LPCD).
Objective
The purpose of this study was to investigate the clinical impact of paced interlead electrical delay and the difference in each conduction time from LV pace to right ventricular (RV) sense (LVp-RVs) and from RV pace to LV sense (RVp-LVs) [(LVp-RVs) - (RVp-LVs)], in CRT.
Methods
Among 137 patients who underwent CRT implantation, LVp-RVs and RVp-LVs were measured intraoperatively. The relationships between [(LVp-RVs) - (RVp-LVs)] and perfusion defects on myocardial perfusion single photon emission computed tomography (SPECT) imaging or [(LVp-RVs) - (RVp-LVs)] and clinical outcomes were also assessed.
Results
After CRT implantation, 81 patients (59%) responded to CRT. [(LVp-RVs) - (RVp-LVs)] was significantly longer in non-responders than in responders (9.7±47.3 vs. -4.5±33.2 ms, p=0.042). Patients with LPCD [(LVp-RVs) > (RVp-LVs)] had higher perfusion defects in the anterolateral region (2.7±2.7 vs. 1.1±1.6, p=0.0015) on SPECT. Multivariate analysis showed that LPCD was the independent predictor of non-response to CRT (odds ratio: 0.40 [95% confidence interval (CI): 0.17-0.90], p=0.026). During a median follow-up of 2.3 years (interquartile range: 1.3-5.5), LPCD was the independent predictor of cardiac death and/or heart failure hospitalization in multivariate analysis (hazard ratio: 1.82, 95%CI: 1.11-3.03, p=0.018).
Conclusions
The LPCD could predict non-response to CRT and poor outcome. Further intervention, such as adjustment of pacing timing or multi-point/site pacing, may be needed in such patients.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 25 May 2020; epub ahead of print
Ueda N, Noda T, Nakajima I, Ishibashi K, ... Yasuda S, Kusano K
Heart Rhythm: 25 May 2020; epub ahead of print | PMID: 32470623
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Abstract

QRS Morphology in Lead V1 for the Rapid Localization of Idiopathic Ventricular Arrhythmias Originating from The Left Ventricular Papillary Muscles: A Novel Electrocardiographic Criterion.

Briceño DF, Santangeli P, Frankel DS, Liang JJ, ... Marchlinski FE, Schaller RD
Background
12-lead electrocardiogram (ECG) criteria have been developed to identify idiopathic ventricular arrhythmias (VAs) from the left ventricular (LV) papillary muscles (PAPs), but accurate localization remains a challenge.
Objective
To develop ECG criteria for accurate localization of LV PAP VAs utilizing lead V1 exclusively.
Methods
Consecutive patients undergoing mapping and ablation of VAs from the LV PAPs guided by intracardiac echocardiography from 2007-2018 were reviewed (study group). The QRS morphology in V1 was compared to patients with VAs with a \"RBBB\" morphology from other LV locations (reference group). Patients with structural heart disease were excluded.
Results
111 patients with LV PAP VAs (age 54±16, male 59%) including 64 (55%) from the posteromedial PAP and 47 (42%) from the anterolateral PAP. The reference group included patients with VAs from the following LV locations: fascicles (n=21), outflow tract (n=36), ostium (n=37), inferobasal segment (n=12), and apex (5). PAP VAs showed 3 distinct QRS morphologies in V1 93% of the time: Rr (53%), R with a slurred downslope (29%), and RR (11%). Sensitivity, specificity, and positive and negative predictive values for the 3 morphologies combined are 93%, 98%, 98%, and 93%, respectively. The intrinsicoid deflection of the PAP VAs in V1 were shorter than the reference group (63±13 ms versus 79±24 ms; p<0.001). An intrinsicoid deflection time less than 74 ms best differentiated the two groups (sensitivity, 79%; specificity, 87%).
Conclusion
VAs originating from the LV PAPs manifest unique QRS morphologies in lead V1, which can aid in rapid and accurate localization.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 22 May 2020; epub ahead of print
Briceño DF, Santangeli P, Frankel DS, Liang JJ, ... Marchlinski FE, Schaller RD
Heart Rhythm: 22 May 2020; epub ahead of print | PMID: 32454219
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Abstract

Comparison of Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction With Versus Without Hyperuricemia or Gout.

Carnicelli AP, Clare R, Chiswell K, Lytle B, ... Roe MT, Mentz RJ

Hyperuricemia and gout are common in patients with heart failure (HF) and are associated with poor outcomes. Data describing hyperuricemia and gout in patients with HF with preserved ejection fraction (HFpEF) are limited. We used data from the Duke University Health System to describe characteristics of patients with HFpEF and hyperuricemia (serum uric acid >6 mg/dl) or gout (gout diagnosis or gout medication within the previous year) and to explore associations with 5-year outcomes (death and hospitalization). We identified 7,004 patients in the Duke University Health System with a known diagnosis of HFpEF who underwent transthoracic echocardiography between January 1, 2005 and December 31, 2017. A total of 1,136 (16.2%) patients with HFpEF also had hyperuricemia or gout. Patients with HFpEF and hyperuricemia or gout had a greater co-morbidity burden, more echocardiographic findings of cardiac remodeling, and higher unadjusted rates of all-cause death, all-cause hospitalization, and HF hospitalization compared with those with HFpEF without hyperuricemia or gout. After multivariable adjustment, patients with HFpEF and hyperuricemia or gout had a significantly higher rates of first all-cause hospitalization (adjusted hazard ratio 1.10 [95% confidence interval 1.02 to 1.19]; p = 0.020) and recurrent all-cause hospitalization (associated rate ratio 1.13 [95% confidence interval 1.01 to 1.25]; p = 0.026). After adjustment, no significant differences in death or HF hospitalization were observed. In conclusion, patients with HFpEF and hyperuricemia or gout were found to have a higher burden of co-morbidities and a higher rate of all-cause hospitalization, even after multivariable adjustment, compared to patients with HFpEF without hyperuricemia or gout.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 21 Apr 2020; epub ahead of print
Carnicelli AP, Clare R, Chiswell K, Lytle B, ... Roe MT, Mentz RJ
Am J Cardiol: 21 Apr 2020; epub ahead of print | PMID: 32386813
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Abstract

Ten-year Outcomes of Transcaval Cardiac Puncture for Catheter Ablation after Extracardiac Fontan Surgery.

Moore JP, Gallotti RG, Tran E, Perens GS, Shannon KM
Background
Though at lower risk, patients with prior extracardiac conduit (EC) Fontan still may require catheter ablation for supraventricular arrhythmia.
Objective
To determine the optimal approach to pulmonary venous access (PVA) after EC Fontan operation.
Methods
All electrophysiologic procedures requiring PVA over a 10-year period at the UCLA Medical Center were reviewed. PVA was grouped by transcaval (TCP) or direct conduit puncture. Procedural characteristics and outcomes were compared.
Results
Between June 2009 and November 2019, 23 electrophysiology procedures requiring PVA access were performed in 17 EC Fontan patients (53% male, median age 25 years [11 - 34]). Cavo-atrial overlap was identified in 14 patients by pre-procedure imaging (10 cardiac CT, 4 cardiac MR). PVA access was obtained via TCP in 11, direct conduit puncture in 6, pre-existing fenestration in 5, and pulmonary artery puncture in 1. Time to PVA was significantly shorter for TCP vs direct conduit puncture (0.2 vs 1.1 hours, respectively; p=0.03). The only predictor of successful TCP was length of cavo-atrial overlap by pre-procedure imaging (14 mm vs 3 mm; p=0.02). There were no procedural complications. No change in oxygen saturation was noted and no evidence of residual shunting was detected by follow up echocardiography.
Conclusions
TCP is feasible in most patients after EC Fontan surgery and can be predicted by pre-procedural advanced imaging. TCP is associated with shorter time to PVA and was uncomplicated in this single center study. Pre-operative assessment of cavo-atrial overlap should be considered prior to catheter ablation for EC Fontan.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 09 May 2020; epub ahead of print
Moore JP, Gallotti RG, Tran E, Perens GS, Shannon KM
Heart Rhythm: 09 May 2020; epub ahead of print | PMID: 32438019
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Abstract

Predictors of change in left-ventricular structure and function in a trial of extended hours hemodialysis.

Smyth B, Chan CT, Grieve SM, Puranik R, ... Perkovic V, Jardine M
Background
Myocardial pathology is common in hemodialysis patients. To explore the effects of different aspects of dialysis treatment on its evolution, we examined the impact of change in markers of volume status, hemodynamics and solute clearance on left ventricular (LV) parameters in a randomized trial of extended dialysis hours.
Methods
ACTIVE Dialysis randomized 200 hemodialysis patients to extended dialysis hours (≥ 24 hours/week) or standard hours (12-18 hours/week) for 12 months. In a pre-specified substudy, 95 participants underwent cardiac magnetic resonance imaging (CMR) at baseline and study end. Generalized linear regression was used to model the relationship between changes LV parameters and markers of volume status (normalized ultrafiltration [UF] rate and total weekly interdialytic weight gain [IDWG]), hemodynamic changes (systolic and diastolic blood pressure [BP]) and solute control (Kt/V, dialysis hours and phosphate).
Results
Randomization to extended hours dialysis was not associated with change in any CMR parameter. Reduction in UF rate was associated with reduction in LV mass index (LVMI) (P=0.049) and improved ejection fraction (EF) (P=0.024); reduction in systolic BP was also associated with improvement in EF (P=0.045); reduction in IDWG was associated with reduced stroke volume (SV) (P=0.038). There were no associations between change in Kt/V, phosphate or total hours per week, and CMR parameters.
Conclusions
Reduction in ultrafiltration rate and blood pressure are associated with improved myocardial parameters in hemodialysis recipients independently of solute clearance or dialysis time. These findings underscore the importance of fluid status and related parameters as potential treatment targets in this population.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 13 Apr 2020; epub ahead of print
Smyth B, Chan CT, Grieve SM, Puranik R, ... Perkovic V, Jardine M
J Card Fail: 13 Apr 2020; epub ahead of print | PMID: 32302717
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Abstract

Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLrApoB mice.

Perazza LR, Mitchell PL, Jensen BAH, Daniel N, ... Mathieu P, Marette A
Background and aims
Poor dietary habits contribute to the obesity pandemic and related cardiovascular diseases but the respective impact of high saturated fat versus added sugar consumption remains debated. Herein, we aimed to disentangle the individual role of dietary fat versus sugar in cardiometabolic disease progression.
Methods
We fed pro-atherogenic LDLrApoB mice either a low-fat/high-sucrose (LFHS) or a high-fat/low-sucrose (HFLS) diet for 24 weeks. Weekly body weight gain was registered. 16S rRNA gene-based gut microbial analysis was performed to investigate gut microbial modulations. Intraperitoneal insulin (ipITT) and oral glucose tolerance test (oGTT) were conducted to assess glucose homeostasis and insulin sensitivity. Cytokines were assessed in fasted plasma, epididymal white adipose tissue and liver lysates. Heart function was evaluated by echocardiography. Aortic atheroma lesions were quantified according to the en face technique.
Results
HFLS feeding increased obesity, insulin resistance and dyslipidemia compared to LFHS feeding. Conversely, high sucrose consumption decreased gut microbial diversity while augmenting inflammation and the adaptative immune defense against metabolic endotoxemia and reduced macrophage cholesterol efflux capacity. This led to more severe cardiovascular complications as revealed by remarkably high level of atherosclerotic lesions and the early development of cardiac dysfunction in LFHS vs HFLS fed mice.
Conclusions
We uncoupled obesity-associated insulin resistance from cardiovascular diseases and provided novel evidence that dietary sucrose, not fat, is the main driver of metabolic inflammation accelerating severe atherosclerosis in hyperlipidemic mice.

Copyright © 2020 Elsevier B.V. All rights reserved.

Atherosclerosis: 23 May 2020; 304:9-21
Perazza LR, Mitchell PL, Jensen BAH, Daniel N, ... Mathieu P, Marette A
Atherosclerosis: 23 May 2020; 304:9-21 | PMID: 32563005
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Abstract

Infective endocarditis in patients with cardiac implantable electronic devices: a nationwide study.

Mateos Gaitán R, Boix-Palop L, Muñoz García P, Mestres CA, ... García Vázquez E, Martínez-Sellés M
Aims
Patients with infective endocarditis (IE) frequently have cardiac implantable electronic devices (CIEDs). Here, we aim to define the clinical profile and prognostic factors of IE in these patients.
Methods and results
Infective endocarditis cases were prospectively identified in the Spanish National Endocarditis Registry. From 3996 IE, 708 (17.7%) had a CIED and 424 CIED-related IE (lead vegetation). Patients with a CIED were older (68 ± 11 vs. 73 ± 8 years); had more comorbidities {pulmonary disease [176 (24.8%) vs. 545 (16.7%)], renal disease [239 (33.8%) vs. 740 (22.7%)], diabetes [248 (35.0%) vs. 867 (26.6%)], and heart failure [348 (49.2%) vs. 978 (29.9%)]}; and fewer complications {intracardiac destruction [106 (15%) vs. 1077 (33.1%)], heart failure [215 (30.3%) vs. 1340 (41.1%)], embolism [107 (15.1%) vs. 714 (21.9%)], and neurological involvement [77 (10.8%) vs. 702 (21.5%)]} (all P-values <0.001) in comparison to subjects without a CIED. In-hospital mortality was similar in patients with and without CIED [171 (24.2%) vs. 881 (27.0%), P = 0.82]. In subjects with a CIED, CIED-related IE was independently associated with in-hospital survival: odds ratio (OR) 0.4 [95% confidence interval (CI) 0.3-0.7, P = 0.001]. Surgery was independently associated with in-hospital survival in CIED-related IE: OR 0.4 (95% CI 0.2-0.7, P = 0.004); but not in subjects with valve IE and no CIED lead involvement: OR 0.9 (95% CI 0.5-1.7, P = 0.77).
Conclusion
Over a sixth of IE patients have a CIED. This group of patients is older, with more comorbidities and fewer IE-related complications in comparison to subjects without a CIED. In-hospital mortality was similar in patients with and without a CIED.

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

Europace: 10 May 2020; epub ahead of print
Mateos Gaitán R, Boix-Palop L, Muñoz García P, Mestres CA, ... García Vázquez E, Martínez-Sellés M
Europace: 10 May 2020; epub ahead of print | PMID: 32390046
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Abstract

Acute coronary syndromes and acute heart failure: a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology.

Harjola VP, Parissis J, Bauersachs J, Brunner-La Rocca HP, ... Weinstein JM, Yilmaz MB

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients.

© 2020 European Society of Cardiology.

Eur J Heart Fail: 28 Apr 2020; epub ahead of print
Harjola VP, Parissis J, Bauersachs J, Brunner-La Rocca HP, ... Weinstein JM, Yilmaz MB
Eur J Heart Fail: 28 Apr 2020; epub ahead of print | PMID: 32347648
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Abstract

Prevalence of atrial FDG uptake and association with atrial arrhythmias in patients with cardiac sarcoidosis.

Yodogawa K, Fukushima Y, Ando T, Iwasaki YK, ... Seino Y, Shimizu W
Background
There is increasing evidence that a proportion of patients with cardiac sarcoidosis (CS) have atrial arrhythmias (AA). Although 18F-fluorodeoxy-glucose (FDG) uptake in the ventricle on positron emission tomography/computed tomography (PET/CT) is well studied, FDG uptake in the atrium has not been elucidated in detail.
Objectives
To evaluate FDG uptake in the atrium and its relationship with AA in patients with CS.
Methods
We retrospectively investigated 62 CS patients. All patients underwent echocardiography and PET/CT. Serum angiotensin converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) levels, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations were also evaluated. ECG, Holter monitoring and device interrogations were used to detect AA.
Results
Of the studied population, 25 patients (40.3%) had AA, of which 2 patients had atrial tachycardia (AT) and 23 patients had atrial fibrillation (AF). Eighteen patients with AA had atrial FDG uptake on PET/CT, whereas 14 patients without AA had atrial FDG uptake (72.0% vs 37.8%, P = 0.017). Multivariate analysis revealed a significant association between AA and age (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 1.01-1.31, P = 0.040), atrial FDG uptake (odds ratio [OR]: 7.23; 95% confidence interval [CI]: 1.91-27.36, P = 0.004), and left atrial diameter (OR: 1.08; 95% CI: 1.01-1.16, P = 0.027). Meanwhile, gender, serum ACE and BNP levels, and left ventricular ejection fraction were not associated with AA.
Conclusions
Atrial FDG uptake was common in patients with CS and strongly associated with AA.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 18 Apr 2020; epub ahead of print
Yodogawa K, Fukushima Y, Ando T, Iwasaki YK, ... Seino Y, Shimizu W
Int J Cardiol: 18 Apr 2020; epub ahead of print | PMID: 32320785
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Abstract

Cardiac Function and Sudden Cardiac Death in Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial).

Kalra R, Gupta K, Sheets R, Aryal S, ... Prabhu SD, Bajaj NS

Patients with heart failure with preserved ejection fraction (HFpEF) have a significantly elevated risk of sudden cardiac death (SCD). However, few imaging data have been correlated to this risk. We evaluated the value of multiple echocardiographic markers of left ventricular (LV) function to predict SCD in HFpEF patients. The Treatment of Heart Failure with Preserved Ejection Fraction with Aldosterone Trial (TOPCAT)-Americas cohort was used to evaluate the echocardiographic predictors of SCD and/or aborted cardiac arrest (SCD/ACA). A retrospective cohort design was used. Cox proportional hazards and Poisson regression models were used to determine the associations between the risk of SCD/ACA and echocardiographic parameters: diastolic dysfunction grade, left ventricle ejection fraction, and LV global longitudinal strain (GLS) during follow-up. Impaired left ventricle ejection fraction and GLS were associated with SCD/ACA in univariate models (p = 0.007 and 0.002, respectively), but not diastolic function grade. After multivariate adjustment, only GLS remained a significant predictor of the incidence rate of SCD/ACA (p = 0.006). There was a 58% increase in the hazard of incident SCD/ACA for every 1 unit increase in GLS (1.58, 95%CI: 1.12 to 2.22, p = 0.009). These findings remained robust in the competing risk analyses. In conclusion, amongst the multiple echocardiographic parameters of LV function, GLS may help prognosticate the risk of SCD/ACA in HFpEF patients.

Published by Elsevier Inc.

Am J Cardiol: 14 May 2020; epub ahead of print
Kalra R, Gupta K, Sheets R, Aryal S, ... Prabhu SD, Bajaj NS
Am J Cardiol: 14 May 2020; epub ahead of print | PMID: 32563496
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Abstract

Risk Stratification in Patients with Non-ischemic Cardiomyopathy and Ventricular Arrhythmias Based on Quantification of Intramural Delayed Enhancement on Cardiac Magnetic Resonance Imaging.

Ghannam M, Siontis KC, Cochet H, Jais P, ... Morady F, Bogun F
Introduction
Intramural scarring is a risk factor for sudden cardiac death. The objective of this study was to determine the value of scar quantification for risk stratification in patients with nonischemic cardiomyopathy (NICM) undergoing ablation procedures for ventricular arrhythmias(VA).
Methods and results
Cardiac late gadolinium-enhanced magnetic resonance imaging was performed in patients with NICM referred for ablation of premature ventricular complexes or ventricular tachycardia (VT). Only patients with intramural delayed enhancement were included. Scar volume was measured and correlated with immediate and longterm outcomes. Receiver operator curves, Wilcoxon signed-rank testing, and logistic regression were used to compare patient characteristics. The study consisted of 99 patients (74 males, mean age: 59.6[54.0-68.1] years, EF: 46.0[35.0-60.0]%). Patients without clinical VT or inducible VT had smaller total and core scar size compared to patients with a history of VT or inducible VT (total scar 1.12[0.74 -1.79] cm vs 7.45[4.16 - 12.21] cm , p<0.001). A total scar volume of ≥2.78 cm was associated with inducibility of VT (AUC 0.94 95% CI[0.89 - 0.98], sensitivity 85%, specificity 90%). Scar volume was associated with VT inducibility independent of a prior history of VT or the pre-procedure EF (adjusted OR 1.67 [1.24-2.24]/cm , P<0.01).
Conclusion
Quantification of scar size in patients with intramural scarring is useful for risk stratification in patients with NICM and VA independent of the EF or a prior history of VT. Scar characteristics of patients without a history of VT who have inducible VT are similar to patients with a history of VT. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 22 Apr 2020; epub ahead of print
Ghannam M, Siontis KC, Cochet H, Jais P, ... Morady F, Bogun F
J Cardiovasc Electrophysiol: 22 Apr 2020; epub ahead of print | PMID: 32329161
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Abstract

Contemporary use of balloon aortic valvuloplasty and evaluation of its success in different hemodynamic entities of severe aortic valve stenosis.

Piayda K, Wimmer AC, Sievert H, Hellhammer K, ... Kelm M, Zeus T
Objectives
To evaluate outcome assessment of percutaneous balloon aortic valvuloplasty (BAV) in different flow and gradient patterns of severe aortic stenosis (AS).
Background
The mean pressure gradient reduction after BAV is an often-used surrogate parameter to evaluate procedural success. The definition of a successful BAV has not been evaluated in different subgroups of severe AS, which were introduced in the latest guidelines on the management of patients with valvular heart disease.
Methods
In this observational study, consecutive patients from July 2009 to March 2018 undergoing BAV were divided into normal-flow high-gradient (NFHG), low-flow low-gradient (LFLG), and paradoxical low-flow low-gradient (pLFLG) AS. Baseline characteristics, hemodynamic, and clinical information were collected and compared.
Results
One-hundred-fifty-six patients were grouped into NFHG (n = 68, 43.5%), LFLG (n = 68, 43.5%), and pLFLG (n = 20, 12.8%) AS. Mean age of the study population was 81 years. Cardiogenic shock or refractory heart failure (46.8%) was the most common underlying reasons for BAV. Spearman correlation revealed that the mean pressure gradient reduction, determined by echocardiography, had a moderate correlation with the increase in the aortic valve area (AVA) in patients with NFHG AS (ρ: 0.529, p < .001) but showed no association in patients with LFLG (ρ: 0.017, p = .289) and pLFLG (ρ: 0.030, p = .889) AS. BAV as bridge to surgical or transcatheter aortic valve replacement was possible in 44.2% of patients, with no difference between groups (p = .070).
Conclusion
The mean pressure gradient reduction might be an adequate surrogate parameter for BAV success in patients with NFHG AS but is not suitable for patients with other hemodynamic entities.

© 2020 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 26 Apr 2020; epub ahead of print
Piayda K, Wimmer AC, Sievert H, Hellhammer K, ... Kelm M, Zeus T
Catheter Cardiovasc Interv: 26 Apr 2020; epub ahead of print | PMID: 32339355
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Abstract

Restoration of sinus rhythm by pulmonary vein isolation improves heart failure with preserved ejection fraction in atrial fibrillation patients.

Rattka M, Pott A, Kühberger A, Weinmann K, ... Rottbauer W, Dahme T
Aims
Atrial fibrillation (AF) in patients suffering from heart failure with preserved ejection fraction (HFpEF) is associated with increased symptoms and higher morbidity and mortality. Effective treatment strategies for this patient population have not yet been established.
Methods and results
We analysed clinical outcomes and echocardiographic parameters of patients with AF and HFpEF who underwent pulmonary vein isolation (PVI). Out of 374 PVI patients, we identified 35 patients suffering from concomitant HFpEF. Freedom from atrial tachyarrhythmia (AT) after 1 year was 80%. Heart failure symptoms assessed by New York Heart Association class significantly improved from 2.7 ± 0.7 to 1.7 ± 0.9 (P < 0.001). We observed regression of diastolic dysfunction by echocardiography 12 months after the index procedure. Moreover, 15 patients (42.9%) experienced complete resolution of HFpEF after a single ablation procedure. Multivariate logistic regression revealed absence of AT recurrence as an independent predictor of recovery from HFpEF (hazard ratio 11.37, 95% confidence interval 1.70-75.84, P = 0.009). Furthermore, resolution of HFpEF by achieving freedom from AT recurrence by PVI, including multiple procedures, led to a significant reduction of hospitalizations.
Conclusion
Our results suggest that restoration of sinus rhythm by PVI in HFpEF patients with concomitant AF induces reverse remodelling, improvement of symptoms, resolution of HFpEF and subsequently decrease of hospitalizations. Randomized controlled trials are warranted to confirm our results.

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

Europace: 24 May 2020; epub ahead of print
Rattka M, Pott A, Kühberger A, Weinmann K, ... Rottbauer W, Dahme T
Europace: 24 May 2020; epub ahead of print | PMID: 32449907
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Abstract

Right Atrial Conduit Phase Emptying Predicts Risk of Adverse Events in Pediatric Pulmonary Arterial Hypertension.

Frank BS, Schafer M, Thomas TM, Haxel C, Ivy DD, Jone PN
Background
Idiopathic pulmonary arterial hypertension (PAH) is a severe disease associated with a 20% 5-year mortality, often due to right heart failure. Recent studies suggest that compensatory changes in right atrial (RA) function may precede other clinical and echocardiographic evidence of right ventricular dysfunction. No prior prospective study has evaluated the role of RA emptying pattern as a prognostic marker of adverse clinical events in pediatric PAH.
Objective
To demonstrate whether RA fractional emptying indices will prospectively predict risk of adverse clinical outcomes in pediatric PAH patients.
Methods
Single-center, prospective cohort analysis of 41 patients with idiopathic or heritable PAH and 1:1 age and sex-matched controls with normal echo and electrocardiogram. Right atrial area (RAA) was measured just prior to tricuspid valve opening (RAAmax), at electrical p wave (RAAp), and just after tricuspid valve closing (RAAmin). Right atrial conduit fraction percent (RA cF%) was defined as the percentage of total RAA change happening prior to the electrical p wave = (RAAmax - RAAp)/(RAAmax - RAAmin) ∗ 100. Clinical worsening was analyzed with a predefined composite adverse event outcome.
Results
RA measurements were technically feasible in all study participants. The PAH patients (median age 11.9 years) had decreased RA cF% compared with controls (P < .0001), and PAH subjects with lower RA cF% demonstrated higher right ventricular systolic (R = -0.49, P = .019) and end-diastolic (R = -0.52, P = .012) pressure than those with higher RA cF%. Sixteen subjects had a clinical event. Right atrial cF% (hazard ratio = 0.09; P < .001) was highly prognostic for risk of adverse clinical event with area under the curve = 0.90 on receiver operating characteristic curve analysis (median 3.2-year follow-up).
Conclusions
Right atrial conduit phase emptying is significantly altered in pediatric PAH. Within the PAH population, decreased RA cF% was prognostic for risk of clinical worsening. The combination of accuracy and ease of measurement could make RA cF% a clinically useful, noninvasive biomarker of early right heart failure and risk of disease progression in pediatric PAH.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 22 Apr 2020; epub ahead of print
Frank BS, Schafer M, Thomas TM, Haxel C, Ivy DD, Jone PN
J Am Soc Echocardiogr: 22 Apr 2020; epub ahead of print | PMID: 32336608
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Abstract

Correlation of magnetic resonance imaging and post-ablation endoscopy to detect oesophageal thermal injury in patients after atrial fibrillation ablation: MRI-EDEL-study.

Halbfass P, Lehmkuhl L, Foldyna B, Berkovitz A, ... Lüsebrink U, Deneke T
Aims
To correlate oesophageal magnetic resonance imaging (MRI) abnormalities with ablation-induced oesophageal injury detected in endoscopy.
Methods and results
Ablation-naïve patients with atrial fibrillation (AF), who underwent ablation using a contact force sensing irrigated radiofrequency ablation catheter, received a cardiac MRI on the day of ablation, and post-ablation oesophageal endoscopy (OE) 1 day after ablation. Two MRI expert readers recorded presence of abnormal oesophageal tissue signal intensities, defined as increased oesophageal signal in T2-fat-saturated (T2fs), short-tau inversion-recovery (STIR), or late gadolinium enhancement (LGE) sequences. Oesophageal endoscopy was performed by experienced operators. Finally, we correlated the presence of any affection with endoscopically detected oesophageal thermal lesions (EDEL). Among 50 consecutive patients (age 67 ± 7 years, 60% male), who received post-ablation MRI and OE, complete MRI data were available in 44 of 50 (88%) patients. In OE, 7 of 50 (14%) presented with EDEL (Category 1 lesion: erosion n = 3, Category 2 lesion: ulcer n = 4). Among those with EDEL, 6 of 7 (86%) patients presented with increased signal intensities in all three MRI sequences, while only 2 of 37 (5%) showed hyperintensities in all three MRI sequences and negative endoscopy. Correspondingly, sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for MRI (increased signal in T2fs, STIR, and LGE) were 86%, 95%, 75%, and 97%, respectively.
Conclusion
Increased signal intensity in T2fs, STIR, and LGE represents independent markers of EDEL. In particular, the combination of all three has the highest diagnostic value. Hence, MRI may represent an accurate, non-invasive method to exclude acute oesophageal injury after AF ablation (NPV: 97%).

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

Europace: 18 May 2020; epub ahead of print
Halbfass P, Lehmkuhl L, Foldyna B, Berkovitz A, ... Lüsebrink U, Deneke T
Europace: 18 May 2020; epub ahead of print | PMID: 32428229
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Abstract

Central role of left atrial dynamics in limiting exercise cardiac output increase and oxygen uptake in heart failure: insights by cardiopulmonary imaging.

Sugimoto T, Barletta M, Bandera F, Generati G, ... Cicoira M, Guazzi M
Aims
In heart failure (HF), the haemodynamic response to exercise in relation to left atrial (LA) dynamics is unexplored. We sought to define whether abnormal LA dynamics during exercise may play a role in cardiac output (CO) limitation and tested its ability to predict outcome.
Methods and results
A total of 195 HF patients with reduced (n = 105), mid-range (n = 48), and preserved (n = 42) left ventricular ejection fraction (LVEF) and 46 non-cardiac dyspnoea (NCD) subjects underwent cardiopulmonary imaging with assessment of LA strain and strain rate (sra). HF patients, irrespective of LVEF, exhibited a significantly impaired LA strain and LA sra at rest, during exercise and recovery compared to NCD subjects with a blunted response in CO and right ventricular to pulmonary circulation coupling. LA strain and LA sra during exertion were significantly correlated with peak stroke volume index, peak CO and peak cardiac power output (R = 0.33, 0.48, 0.50 and R = 0.36, 0.51, 0.52 for LA strain and LA sra, respectively; all P < 0.001). In HF, after adjustment for age, gender, left atrial volume index, peak mitral regurgitation > 2, peak LVEF and peak heart rate, a higher LA strain (1% increase) during exercise was associated with a higher peak stroke volume index (mL/m ), CO (L/min) and cardiac power output (mmHg L/min) at multivariable analyses (β-coefficients ± standard error = 0.23 ± 0.07, 0.046 ± 0.014 and 0.012 ± 0.004, respectively; P < 0.05). The same associations were found also for LA sra (absolute value) (1/s increase, β-coefficients ± standard error = 1.91 ± 0.68, 0.43 ± 0.14 and 0.12 ± 0.04, respectively; P < 0.05). Exercise LA strain (adjusted hazard ratio 0.94, 95% confidence interval 0.92-0.97, P < 0.001) and LA sra (adjusted hazard ratio 0.60, 95% confidence interval 0.43-0.84, P = 0.003) were associated with a worse outcome after adjusting for age and gender.
Conclusions
In HF, LA dynamics may play a key role in exercise CO increase due to an impaired forward (left ventricular filling) and backward (right ventricular to pulmonary circulation uncoupling) combination of mechanisms, irrespective of LVEF. The blunted LA strain and LA sra reserve during exercise are associated with a worse cardiopulmonary performance and outcome.

© 2020 European Society of Cardiology.

Eur J Heart Fail: 29 Apr 2020; epub ahead of print
Sugimoto T, Barletta M, Bandera F, Generati G, ... Cicoira M, Guazzi M
Eur J Heart Fail: 29 Apr 2020; epub ahead of print | PMID: 32352628
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Abstract

Heart Rate, Brain Imaging Biomarkers and Cognitive Impairment in Older (≥63 years) Women.

Haring B, Liu J, Rapp SR, Shimbo D, ... Espeland M, Wassertheil-Smoller S

Evidence on the relations between heart rate, brain morphology, and cognition is limited. We examined the associations of resting heart rate (RHR), visit-to-visit heart rate variation (VVHRV), brain volumes and cognitive impairment. The study sample consisted of postmenopausal women enrolled in the Women\'s Health Initiative Memory Study and its ancillary MRI sub-studies (WHIMS-MRI 1 and WHIMS-MRI 2) without a history of cardiovascular disease, including 493 with one and 299 women with 2 brain magnetic resonance imaging (MRI) scans. HR readings were acquired annually starting from baseline visit (1996-1998). RHR was calculated as the mean and VVHRV as standard deviation of all available HR readings. Brain MRI scans were performed between 2005 and 2006 (WHIMS-MRI 1), and approximately 5 years later (WHIMS-MRI 2). Cognitive impairment was defined as incident mild cognitive impairment or probable dementia until December 30, 2017. An elevated RHR was associated with greater brain lesion volumes at the first MRI exam (7.86 cm3 [6.48, 9.24] vs 4.78 cm3 [3.39, 6.17], p-value <0.0001) and with significant increases in lesion volumes between brain MRI exams (6.20 cm3 [4.81, 7.59] vs 4.28 cm3 [2.84, 5.73], p-value = 0.0168). Larger ischemic lesion volumes were associated with a higher risk for cognitive impairment (Hazard Ratio [95% confidence interval], 2.02 [1.18, 3.47], p-value = 0.0109). Neither RHR nor VVHRV were related to cognitive impairment. In sensitivity analyses, we additionally included women with a history of cardiovascular disease to the study sample. The main results were consistent to those without a history of cardiovascular disease. In conclusion, these findings show an association between elevated RHR and ischemic brain lesions, probably due to underlying subclinical disease processes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 25 May 2020; epub ahead of print
Haring B, Liu J, Rapp SR, Shimbo D, ... Espeland M, Wassertheil-Smoller S
Am J Cardiol: 25 May 2020; epub ahead of print | PMID: 32576368
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Abstract

Carotid intima-media thickness and subclinical left heart dysfunction in the general population.

Nakanishi K, Daimon M, Yoshida Y, Ishiwata J, ... Homma S, Komuro I
Background and aims
Although carotid intima-media thickness (IMT) is an established marker of atherosclerosis and carries independent risk for cardiovascular disease, its possible association with subclinical cardiac dysfunction has not been extensively evaluated. Left ventricular global longitudinal strain (LVGLS) and peak left atrial longitudinal systolic strain (PALS) can detect subclinical left heart dysfunction. This study aimed to investigate the association between carotid IMT and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease.
Methods
We examined 1161 participants who underwent extensive cardiovascular examination. Ultrasonography of common carotid artery was performed for the measurement of maximal carotid IMT. LVGLS and PALS were assessed by 2-dimensional speckle-tracking echocardiography.
Results
Mean age was 62 ± 12 years, and 56% were male. The prevalence of abnormal LVGLS (>-18.6%) and PALS (<31.4%) was greatest in the upper quartile of carotid IMT (both p < 0.001). In multivariable analyses, carotid IMT was associated with abnormal LVGLS (adjusted odds ratio = 1.33 per 1SD increase of IMT, p = 0.003) as well as PALS (adjusted odds ratio = 1.33 per 1SD increase of IMT, p = 0.005) independent of traditional cardiovascular risk factors, echocardiographic parameters including LV ejection fraction, LV mass index and diastolic dysfunction, and pertinent laboratory parameters. The independent association between carotid IMT and PALS persisted even after adjustment for LVGLS.
Conclusions
Participants with increased IMT had significantly impaired LV and LA function in an unselected community-based cohort. This association may be involved in the higher incidence of cardiovascular disease in individuals with increased carotid IMT.

Copyright © 2020 Elsevier B.V. All rights reserved.

Atherosclerosis: 14 Jun 2020; 305:42-49
Nakanishi K, Daimon M, Yoshida Y, Ishiwata J, ... Homma S, Komuro I
Atherosclerosis: 14 Jun 2020; 305:42-49 | PMID: 32629183
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Abstract

Comparison of Outcomes in Patients With Heart Failure With Versus Without Lead-Induced Tricuspid Regurgitation After Cardiac Implantable Electronic Devices Implantations.

Seo Y, Nakajima H, Ishizu T, Iida N, ... Ohte N, Ieda M

Cardiac implantable electronic devices (CIED) implantations may cause lead-induced tricuspid regurgitation (LITR). Although patients with CIED have the risk of functional non-lead induced TR (Non-LITR). This study aimed to compare of clinical outcome between LITR and Non-LITR. The mechanism of TR was determined by 3-dimensional echocardiography. The primary end point was heart failure (HF) hospitalizations after CIED implantation. In patients with HF events, subsequent clinical outcomes after HF hospitalization were compared between no TR, LITR, and Non-LITR groups. In eligible 373 patients, 67 patients had HF hospitalization, of whom worsened TR was observed in 49 patients. In the remaining 307 patients, worsened TR was observed in only 10 patients (3.3%). Of the 49 patients with worsened TR, 18 patients (37%) had LITR. In 67 patients with HF hospitalization, 25 patients (37%) met rehospitalization. All severe LITR persisted after HF events. Meanwhile, severe Non-LITR improved to moderate or mild level. Cox proportional hazard model analyses revealed LITR was the independent risk factor of rehospitalization. Both LITR and Non-LITR were common at HF events after CIED implantations. However, LITR persisted and might contribute to a worse prognosis. In patients with TR after CIED implantations, 3-dimensional echocardiography should be performed to diagnose the LITR accurately, which may contribute to improving the clinical outcome.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 06 Jun 2020; epub ahead of print
Seo Y, Nakajima H, Ishizu T, Iida N, ... Ohte N, Ieda M
Am J Cardiol: 06 Jun 2020; epub ahead of print | PMID: 32622503
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Abstract

Effectiveness and Safety of the ACURATE Neo Prosthesis in 1,000 Patients With Aortic Stenosis.

Kim WK, Möllmann H, Liebetrau C, Renker M, Walther T, Hamm CW

The ACURATE neo transcatheter heart valve has demonstrated a balanced profile with low rates of permanent pacemaker implantation, low risk of coronary obstruction, and favorable hemodynamic properties whilst having an acceptable rate of ≥moderate paravalvular leakage (PVL). Here, we report in-hospital results and assess the learning curve for implantation of the ACURATE neo device in a large, single-center cohort. The cohort of this retrospective, observational study comprised 1,000 consecutive patients with severe aortic stenosis who underwent transfemoral transcatheter aortic valve implantation using the ACURATE neo prosthesis between May 2012 and December 2019. We determined procedural outcomes with emphasis on PVL and analyzed the learning curve. The median age was 81.9 years [IQR 78.8; 85.1], and the Euroscore II was 4.2% [IQR 2.7; 7.3]. The rate of PVL ≥moderate measured by echocardiography at discharge was 3.7% (37 of 988). We observed a learning curve, with a decline in ≥moderate PVL from 6.7% in the first quartile to 0.8% in the last quartile, that was related to better patient selection, more oversizing, and consideration of the amount and distribution of aortic valve calcification. In this thus far largest single-center experience using the ACURATE neo prosthesis, we demonstrate that after completing a learning curve and observation of precepts that include patient selection, careful sizing, and procedural aspects, the rate of ≥moderate PVL may be reduced to <1%.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 06 Jun 2020; epub ahead of print
Kim WK, Möllmann H, Liebetrau C, Renker M, Walther T, Hamm CW
Am J Cardiol: 06 Jun 2020; epub ahead of print | PMID: 32622500
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Abstract

Plasma levels of soluble TNF receptors are associated with cardiac function in patients with Chagas heart disease.

Silva WT, Costa HS, de Lima VP, Xavier DM, ... Rocha MOC, Figueiredo PHS
Background
The soluble receptors tumor necrosis factor-alpha (sTNFRs) can lead to an increase in the expression of tumor necrosis factor, increasing its detrimental to systemic inflammatory activation in Chagas cardiomyopathy (ChC). However, the correlation between sTNFRs levels, echocardiographic, and functional levels in patients with ChC remains unknown. This study aimed to verify the correlation between the plasma sTNFRs levels, echocardiographic, and NYHA functional levels in patients with ChC.
Methods
Sixty-four patients with ChD (54 ± 2 years, 44% males, NYHA I-II) were evaluated by anamnesis protocol, echocardiography, and plasma sTNFR1 and sTNFR2 measurement. Linear regression analysis and Student\'s t-test were used as appropriate.
Results
Higher plasma sTNFR1 and sTNFR2 levels were associate with worse systolic function (R2 = 0.10; p = 0.008 and R2 = 0.44; p < 0.001) and cardiac dilation (R2 = 0.13; p = 0.002 and R2 = 0.43; p < 0.001). Patients with systolic dysfunction and cardiac dilatation had higher sTNFRs levels (p < 0.001). There were no significant differences among NYHA functional classes for both sTNFRs.
Conclusion
Plasma sTNFR1 and sTNFR2 levels are associated with greater cardiac dilation and poor systolic function in ChC patients.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 18 Apr 2020; epub ahead of print
Silva WT, Costa HS, de Lima VP, Xavier DM, ... Rocha MOC, Figueiredo PHS
Int J Cardiol: 18 Apr 2020; epub ahead of print | PMID: 32320786
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Impact:
Abstract

High-intensity endurance training is associated with left atrial fibrosis.

Peritz DC, Catino AB, Csecs I, Kaur G, ... Morris A, Marrouche NF
Introduction
Endurance athletes are at higher risk for developing atrial fibrillation as compared to the general population. The exact mechanism to explain this observation is incompletely understood. Our study aimed to determine whether degree of left atrial fibrosis detected by late gadolinium-enhancement magnetic resonance imaging (LGE-MRI) differed between Masters athletes and non-athlete controls.
Methods
We recruited 20 endurance healthy Masters athletes and 20 healthy control subjects who underwent cardiac MRI. Healthy controls were recruited during screening colonoscopies and Masters athletes were recruited through word of mouth and at competitions. The two groups were age and gender matched. None of the participants were known to have an arrhythmia. Fibrosis, as measured by late gadolinium-enhancement, was measured in each participant by blinded readers. The degree of left atrial fibrosis was compared between the two groups. All participants were recruited from the Salt Lake City region and scanned at the University of Utah healthcare complex.
Results
Left ventricular function was normal in all study participants. Left atrial volumes were significantly larger in the athletes (74.2 ml ± 14.4) as compared to the healthy control subjects (60.8 mL ± 21.4) (P = .02). Mean left atrial fibrosis score, reported as a percentage of the LA, was 15.5% ± 5.9 in the athlete cohort compared to 9.6% ± 4.9 in the controls (P = .002).
Conclusions
To our knowledge this is the first study that describes, characterizes and specifically quantifies fibrotic changes within the left atrium of highly trained endurance athletes. Increased atrial fibrosis seen in this population may be an early indicator for endurance athletes at risk of developing atrial arrhythmias.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 29 May 2020; 226:206-213
Peritz DC, Catino AB, Csecs I, Kaur G, ... Morris A, Marrouche NF
Am Heart J: 29 May 2020; 226:206-213 | PMID: 32615358
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Abstract

Characteristics and Prognostic Associations of Echocardiographic Pulmonary Hypertension With Normal Left Ventricular Systolic Function in Patients ≥90 Years of Age.

Shimada S, Uno G, Omori T, Rader F, Siegel RJ, Shiota T

The high prevalence of pulmonary hypertension (PH) in elderly patients is well known. However, much remains unknown about those population. We sought to find the clinical characteristics of echocardiographic PH and the prognostic factors in patients ≥90 years of age. We retrospectively reviewed 310 patients ≥90 years of age (median age 92 years, 64% women) diagnosed as echocardiographic PH (peak systolic pulmonary arterial pressure ≥40 mm Hg) with normal left ventricular systolic function. We defined left heart disease (LHD) as significant left-sided valve diseases, left ventricular hypertrophy and left ventricular diastolic dysfunction by using echocardiography. The endpoint was all-cause death at 2,000 days after diagnosis. LHD was found in 92% of patients. During the median follow-up of 367 days (interquartile range, 39-1,028 days), 151 all-cause deaths (49%) occurred. Multivariable Cox regression analysis demonstrated that right ventricular fraction area change <35% (adjusted hazard ratio [HR]: 2.31; p <0.001), pericardial effusion (adjusted HR: 2.28; p <0.001), serum albumin <3.5 g/dL (adjusted HR: 1.76; p = 0.001), chronic obstructive pulmonary disease (adjusted HR: 1.93; p = 0.001) and New York Heart Association (NYHA) class ≥II (adjusted HR: 1.73; p = 0.004) were associated with mortality after adjusted for age. In conclusion, LHD was significantly associated with echocardiographic PH in most patients ≥90 years of age. Also, the co-morbid factors at diagnosis (right ventricular systolic dysfunction, pericardial effusion, hypoalbuminemia, chronic obstructive pulmonary disease, and NYHA class ≥II) were independently associated with mortality.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 25 May 2020; epub ahead of print
Shimada S, Uno G, Omori T, Rader F, Siegel RJ, Shiota T
Am J Cardiol: 25 May 2020; epub ahead of print | PMID: 32624190
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Impact:
Abstract

Echocardiography in the Era of Obesity.

El Hajj MC, Litwin SE

Patients with obesity are at increased risk for coronary artery disease and heart failure and often present with symptoms of dyspnea, fatigue, edema, or chest pain. Echocardiography is frequently used to help distinguish whether these symptoms are due to cardiac disease. Unfortunately, obesity has a significant impact on image quality because of signal attenuation. Ultrasound-enhancing agents may improve the detection of structural remodeling and subclinical left ventricular dysfunction in patients with obesity. Assessment of chamber sizes and cardiac remodeling in severely obese subjects must be interpreted with caution, however, as the current recommendations for indexing cardiac chamber sizes to body size may lead to false conclusions about chamber volumes or mass, particularly in settings in which weight is changing. As a result of increases in stroke volume and cardiac output, obesity may exacerbate hemodynamic compromise in obstructive structural or valvular disease. With regard to assessment of ischemic heart disease, stress echocardiography can effectively risk-stratify patients with obesity and may have advantages over other noninvasive modalities. In general, transesophageal echocardiography is safe in patients with obesity, although some precautions should be observed. Stress echocardiography using the transesophageal approach is an alternative for preoperative or ischemia evaluation in patients with suboptimal transthoracic views.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Apr 2020; epub ahead of print
El Hajj MC, Litwin SE
J Am Soc Echocardiogr: 27 Apr 2020; epub ahead of print | PMID: 32359803
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Impact:
Abstract

Sex Differences in the Association of Cumulative Body Mass Index from Early Adulthood to Middle Age and Left Atrial Remodeling Evaluated by Three-Dimensional Echocardiography: The Coronary Artery Risk Development in Young Adults Study.

Doria de Vasconcellos H, Betoko A, Ciuffo LA, Moreira HT, ... Gidding SS, Lima JAC
Background
The relationship between long-term obesity and left atrial (LA) structure and function is not entirely understood. We examined the association of cumulative body mass index (cBMI) with LA remodeling using three-dimensional (3D) speckle-tracking echocardiography (STE).
Methods
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a community-based cohort of black and white, men and women, ages 18-30 years at baseline in 1985-86 from four U.S. centers. This study included 2,144 participants who had satisfactory image quality and body mass index measurements during the entire follow-up period. The 3D STE-derived LA parameters were maximum, minimum, and pretrial contraction volumes; total, passive, and active emptying fraction; maximum systolic longitudinal strain; and early and late diastolic longitudinal strain rates. Multivariable linear regression analyses stratified by sex assessed the relationship between cBMI and 3D STE-derived LA parameters, adjusting for demographics and traditional cardiovascular.
Results
The mean age of the cohort was 55 ± 3.6 years; 54.8% were women, and 46.5% were black. There were statistically significant additive sex interactions for the association between cBMI and LA minimum contraction value, maximum systolic longitudinal strain, and early and late diastolic longitudinal strain rates. In the fully adjusted model, greater cBMI was associated with lower magnitude LA longitudinal deformation (maximum systolic longitudinal strain and early and late diastolic longitudinal strain rates) in men and with higher LA emptying fraction in women. In addition, greater cBMI was associated with higher LA phasic volumes indices in both men and women.
Conclusions
This study showed that while greater cBMI from early adulthood throughout middle age was associated with higher LA volumes in both genders, differences were found for LA function, with lower longitudinal deformation in men and higher reservoir and active LA function in women.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 22 Apr 2020; epub ahead of print
Doria de Vasconcellos H, Betoko A, Ciuffo LA, Moreira HT, ... Gidding SS, Lima JAC
J Am Soc Echocardiogr: 22 Apr 2020; epub ahead of print | PMID: 32336609
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Impact:
Abstract

Differences between gap-related persistent conduction and carina-related persistent conduction during radiofrequency pulmonary vein isolation.

Mulder MJ, Kemme MJB, Götte MJW, van de Ven PM, ... van Rossum AC, Allaart CP
Background
During pulmonary vein isolation (PVI), non-isolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the WACA (wide-area circumferential ablation) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap-related persistent conduction (gap-RPC) and carina-related persistent conduction (carina-RPC) during PVI.
Methods and results
Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62±9 years) undergoing first contact force-guided radiofrequency PVI were studied. Pre-procedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap-RPC or carina-RPC, depending on the earliest activation site. The 1-year AF recurrence rate was higher in patients with gap-RPC (47%) compared to patients without gap-RPC (28%; p=0.003). No significant difference in 1-year recurrence rate was found between patients with carina-RPC (37%) and patients without carina-RPC (31%, p=0.379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap-RPC, whereas carina width and WACA circumference correlated with carina-RPC.
Conclusions
Gap-RPC is associated with increased AF recurrence risk after PVI, whereas carina-RPC does not predict AF recurrence. Moreover, gap-RPC and carina-RPC have different correlates and may thus have different underlying mechanisms. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 12 May 2020; epub ahead of print
Mulder MJ, Kemme MJB, Götte MJW, van de Ven PM, ... van Rossum AC, Allaart CP
J Cardiovasc Electrophysiol: 12 May 2020; epub ahead of print | PMID: 32406138
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Impact:
Abstract

Invasive strategy for COVID patients presenting with acute coronary syndrome: The first multicenter Italian experience.

Secco GG, Tarantini G, Mazzarotto P, Garbo R, ... Centini G, Di Mario C
Objective
To report our initial experience of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/acute coronary syndrome (ACS) patients undergoing standard of care invasive management.
Background
The rapid diffusion of the SARS-CoV-2 together with the need for isolation for infected patients might be responsible for a suboptimal treatment for SARS-CoV-2 ACS patients. Recently, the group of Sichuan published a protocol for COVID/ACS infected patients that see the thrombolysis as the gold standard of care.
Methods
We enrolled 31 consecutive patients affected by SARS-COV-2 admitted to our emergencies room for suspected ACS.
Results
All patients underwent urgent coronary angiography and percutaneous coronary intervention (PCI) when required except two patients with severe hypoxemia and unstable hemodynamic condition that were conservatively treated. Twenty-one cases presented diffuse ST-segment depression while in the remaining cases anterior and inferior ST-elevation was present in four and six cases, respectively. PCI was performed in all cases expect two that were diagnosed as suspected myocarditis because of the absence of severe coronary disease and three with apical ballooning at ventriculography diagnostic for Tako-Tsubo syndromes. Two patients conservatively treated died. The remaining patients undergoing PCI survived except one that required endotracheal intubation (ETI) and died at Day 6. ETI was required in five more patients while in the remaining cases CPAP was used for respiratory support.
Conclusions
Urgent PCI for ACS is often required in SARS-CoV-2 patients improving the prognosis in all but the most advanced patients. Complete patient history and examination, routine ECG monitoring, echocardiography, and careful evaluation of changes in cardiac enzymes should be part of the regular assessment procedures also in dedicated COVID positive units.

© 2020 Wiley Periodicals, Inc.

Catheter Cardiovasc Interv: 11 May 2020; epub ahead of print
Secco GG, Tarantini G, Mazzarotto P, Garbo R, ... Centini G, Di Mario C
Catheter Cardiovasc Interv: 11 May 2020; epub ahead of print | PMID: 32400049
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Impact:
Abstract

Identification of KIAA0196 as a novel susceptibility gene for myofibril structural disorganization in cardiac development.

Bu H, Yang Y, Wu Q, Tan Z, ... Hu S, Zhao T
Background
Congenital heart disease is one of the most common cardiac malformation-related diseases worldwide. Some causative genes have been identified but can explain only a small proportion of all cases; therefore, the discovery of novel susceptibility genes and/or modifier genes for abnormal cardiac development remains a major challenge.
Methods
We used a single nucleotide polymorphism (SNP) array, and next-generation sequencing (NGS) was conducted to screen and quickly identify candidate genes. KIAA0196 knockout zebrafish and mice were generated by CRISPR/Cas9 to detect whether or how KIAA0196 deficiency would influence cardiac development.
Results
Homozygous, but not heterozygous, zebrafish and mice showed early embryonic lethality. At the embryonic stage, microscopic examination and dissection revealed pericardial edema and ventricle enlargement in homozygous zebrafish and obviously delayed cardiac development in heterozygous mice, while echocardiography and tissue staining showed that significantly decreased cardiac function, ventricle enlargement, myofibril loss, and significantly reduced trabecular muscle density were observed in adult heterozygous zebrafish and mice. Most importantly, immunostaining and electron microscopy showed that there was a significant increase in sarcomere structural disorganization and myofibril structural integrity loss in KIAA0196 mutants. Furthermore, substantial downregulation in other sarcomeric genes and proteins was detected and verified in a mouse model via transcriptome and proteomics analyses; these changes especially affected the myosin heavy or light chain (MYH or MYL) family genes.
Conclusion
We identified KIAA0196 for the first time as a susceptibility gene for abnormal cardiac development. KIAA0196 deficiency may cause abnormal heart development by influencing the structural integrity of myofibrils.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 13 May 2020; epub ahead of print
Bu H, Yang Y, Wu Q, Tan Z, ... Hu S, Zhao T
Int J Cardiol: 13 May 2020; epub ahead of print | PMID: 32417190
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Abstract

Noninvasive Leg-Positive Pressure Stress Echocardiography Reveals Preload Reserve in Adult Patients after Complete Repair of Tetralogy of Fallot.

Suto M, Matsumoto K, Onishi A, Shibata N, ... Tanaka H, Hirata KI
Background
Long-term sequelae such as right ventricular dysfunction and reduced hemodynamic reserve are the main determinants of cardiovascular outcomes after repair of tetralogy of Fallot (TOF). Echocardiographic parameters at rest offer only partial information on impaired hemodynamics in these patients, and data during stress testing are lacking. The leg-positive pressure (LPP) maneuver has recently been reported to be able to apply acute preload stress. The aim of this study was to test the hypothesis that preload reserve is impaired and ventricular interaction is exacerbated in patients with TOF.
Methods
In this prospective cross-sectional study, we recruited 44 consecutive patients with TOF and 30 normal control subjects. Echocardiography was performed both at rest and during LPP stress, and preload reserve was defined as the change between baseline stroke volume (SV) and that obtained during LPP stress. The eccentricity index was calculated as the ratio of the left ventricular anteroposterior to septal-lateral dimensions to quantify ventricular interaction.
Results
LPP stress significantly increased SV from 73 ± 14 to 83 ± 16 mL (P < .01) in control subjects, while the increase in SV was significantly blunted (from 75 ± 19 to 79 ± 18 mL; P < .01 for interaction) in patients with TOF. The eccentricity index significantly changed during LPP stress in patients with TOF only from 1.07 ± 0.13 to 1.13 ± 0.14 (P < .01 for interaction). Patients with TOF were subdivided into two subgroups on the basis of the median value of increased response in SV (22 with sufficient and 22 with insufficient preload reserve). Multivariate analysis identified significant pulmonary regurgitation as the only independent determinant factor for insufficient preload reserve (odds ratio, 4.57; 95% CI, 1.048-19.90; P = .04).
Conclusions
In patients after repair of TOF, ventricular interaction was exacerbated and preload reserve was impaired, especially in patients with significant pulmonary regurgitation. LPP stress testing may direct tailored treatment approaches, risk stratification, and clinical decision-making, such as more aggressive pharmacologic therapy, meticulous outpatient follow-up, or earlier reintervention.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 22 Apr 2020; epub ahead of print
Suto M, Matsumoto K, Onishi A, Shibata N, ... Tanaka H, Hirata KI
J Am Soc Echocardiogr: 22 Apr 2020; epub ahead of print | PMID: 32336610
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Impact:
Abstract

New Comprehensive Reference Values for Arterial Vascular Parameters in Children.

Torigoe T, Dallaire F, Slorach C, Cardinal MP, ... Mertens L, Jaeggi E
Background
Noninvasive measurements of vascular parameters can be used for the detection and risk stratification of cardiovascular diseases. Most vascular parameters are influenced by age and body size, but pediatric reference values are scarce and limited to a few parameters. The aim of this study was to develop pediatric reference values and Z score equations for a comprehensive set of vascular parameters.
Methods
A total of 292 healthy subjects aged 0 to 18 years were prospectively recruited. Stiffness index β, pressure-strain elastic modulus, common carotid intima-media thickness, brachial flow-mediated dilation, radial augmentation index, central and right arm peripheral artery pulse-wave velocities, and pulse-wave velocity ratio were assessed. Normalization for age and anthropometric variables was performed using parametric multivariate regression modeling. Z scores were assessed for heteroscedasticity, residual association with age and body size, and distribution.
Results
Multivariate regression models with various combinations of height, weight, and age were used to obtain Z scores that were independent of age and body size. There was no residual association between Z scores and body size, age, or body mass index. There was no significant departure from the normal distribution.
Conclusions
The authors present reference values and Z score equations for a comprehensive set of vascular parameters during childhood. Further studies are necessary to assess their usefulness in detecting the vascular signs of subclinical atherosclerosis and chronic diseases, including congenital heart disease.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 18 May 2020; epub ahead of print
Torigoe T, Dallaire F, Slorach C, Cardinal MP, ... Mertens L, Jaeggi E
J Am Soc Echocardiogr: 18 May 2020; epub ahead of print | PMID: 32444330
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Impact:
Abstract

Pulmonary hypertension and right ventricular dysfunction in heart failure: prognosis and 15-year prospective longitudinal trajectories in survivors.

Santiago-Vacas E, Lupón J, Gavidia-Bovadilla G, Gual-Capllonch F, ... Santesmases J, Bayes-Genis A
Aims
Systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/SPAP ratio trajectories are not fully characterized in chronic heart failure (HF). We assessed very long-term longitudinal SPAP, TAPSE and TAPSE/SPAP trajectories in HF patients, and their dynamic changes in outcomes.
Methods and results
Prospective, consecutive, observational registry of real-life HF patients, performing echocardiography studies at baseline and according to a prospectively structured schedule after 1 year, and then every 2 years, up to 15 years. Pulmonary hypertension (PH) was defined as SPAP ≥40 mmHg; right ventricular dysfunction (RVD) was defined at TAPSE ≤16 mm; and TAPSE/SPAP ratio was dichotomized at 0.36 mm/mmHg. The clinical endpoints were all-cause death, the composite endpoint of mortality or HF hospitalization and the number of recurrent HF hospitalizations. The study cohort included 1557 patients. Long-term SPAP trajectory Loess curves were U-shaped with a nadir at 7 years. TAPSE Loess curves showed a marked rise during the first year, with stabilization thereafter. TAPSE/SPAP ratio Loess splines were similar to the later with a smooth decline towards the end. Patients who died had higher SPAP, lower TAPSE and lower TAPSE/SPAP ratio in the preceding period than survivors. Baseline PH and/or RVD were independently associated with mortality and HF-related hospitalizations, and the persistence of one or both entities at 1 year conferred a worse long-term prognosis.
Conclusions
Long-term trajectories for SPAP, TAPSE and TAPSE/SPAP ratio are reported in patients with chronic HF. An increasing SPAP and declining TAPSE and TAPSE/SPAP ratio in the preceding period is associated with higher mortality.

© 2020 European Society of Cardiology.

Eur J Heart Fail: 24 May 2020; epub ahead of print
Santiago-Vacas E, Lupón J, Gavidia-Bovadilla G, Gual-Capllonch F, ... Santesmases J, Bayes-Genis A
Eur J Heart Fail: 24 May 2020; epub ahead of print | PMID: 32452102
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Impact:
Abstract

Evaluation of the right heart using cardiovascular magnetic resonance imaging in patients with cardiac devices.

Löbe S, Paetsch I, Hilbert S, Spampinato R, ... Hindricks G, Jahnke C
Background
Patients with cardiac implantable electronic devices (CIED) necessitate comprehensive cardiovascular magnetic resonance (CMR) examinations. The aim of this study was to provide data on CMR image quality and feasibility of functional assessment of the right heart in patients with CIED depending on the device type and imaging sequence used.
Methods
120 CIED carriers (Insertable cardiac monitoring system, n = 13; implantable loop-recorder, n = 22; pacemaker, n = 30; implantable cardioverter-defibrillator (ICD), n = 43; and cardiac resynchronization therapy defibrillator (CRT-D), n = 12) underwent clinically indicated CMR imaging using a 1.5 T. CMR protocols consisted of cine imaging and myocardial tissue characterization including T1-and T2-weighted blackblood imaging and late gadolinium enhancement (LGE) imaging. Image quality was evaluated with regard to device-related imaging artifacts per right-ventricular (RV) segment.
Results
RV segmental evaluability was influenced by the device type and CMR imaging sequence: Cine steady-state-free-precision (SSFP) imaging was found to be non-diagnostic in patients with ICD/CRT-D and implantable loop recorders; a significant improvement of image quality was achieved when using cine turbo-field-echo (TFE) sequences with a further improvement on post-contrast TFE imaging. LGE scans were artifact-free in at least 91% of RV segments with best results in patients with a pacemaker or an insertable cardiac monitoring system.
Conclusions
In patients with CIED, artifact-free CMR imaging of the right ventricle was performed in the majority of patients and resulted in highly reproducible evaluability of RV functional parameters. This finding is of particular importance for the diagnosis and follow-up of right-ventricular diseases.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 06 May 2020; epub ahead of print
Löbe S, Paetsch I, Hilbert S, Spampinato R, ... Hindricks G, Jahnke C
Int J Cardiol: 06 May 2020; epub ahead of print | PMID: 32389768
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Abstract

Prolonged left ventricular contraction duration in apical segments as a marker of arrhythmic risk in patients with long QT syndrome.

Borowiec K, Kowalski M, Kumor M, Duliban J, ... Hoffman P, Biernacka EK
Aims
Long QT syndrome (LQTS) is an inherited cardiac ion channelopathy predisposing to life-threatening ventricular arrhythmias and sudden cardiac death. The aim of this study was to investigate left ventricular mechanical abnormalities in LQTS patients and establish a potential role of strain as a marker of arrhythmic risk.
Methods and results
We included 47 patients with genetically confirmed LQTS (22 LQT1, 20 LQT2, 3 LQT3, and 2 SCN3B) and 25 healthy controls. A history of cardiac events was present in 30 LQTS subjects. Tissue Doppler and speckle tracking echocardiography were performed and contraction duration was measured by radial and longitudinal strain. The radial strain characteristic was subdivided into two planes - the basal and the apical. Left ventricular ejection fraction and global longitudinal strain were normal in LQTS patients. Mean contraction duration was longer in LQTS patients compared with controls in regard to basal radial strain (491 ± 57 vs. 437 ± 55 ms, P < 0.001), apical radial strain (450 ± 53 vs. 407 ± 53 ms, P = 0.002), and longitudinal strain (445 ± 34 vs. 423 ± 43 ms, P = 0.02). Moreover, contraction duration obtained from apical radial strain analysis was longer in symptomatic compared with asymptomatic LQTS mutation carriers (462 ± 49 vs. 429 ± 55 ms, P = 0.024), as well as in subject with mutations other than LQT1 considered to be at higher risk (468 ± 50 vs. 429 ± 49 ms, P = 0.01).
Conclusion
Myocardial contraction duration is prolonged for both radial and longitudinal directions in LQTS patients. Regional left ventricular function analysis may contribute to risk stratification. Apical radial deformation seems to select subjects at higher risk of arrhythmic events.

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

Europace: 11 Jun 2020; epub ahead of print
Borowiec K, Kowalski M, Kumor M, Duliban J, ... Hoffman P, Biernacka EK
Europace: 11 Jun 2020; epub ahead of print | PMID: 32529202
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Abstract

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

D\'Silva A, Captur G, Bhuva AN, Jones S, ... Moon JC, Sharma S
Background
Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation.
Methods
Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study.
Results
After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy.
Conclusion
Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis.

Copyright © 2018. Published by Elsevier B.V.

Int J Cardiol: 28 Apr 2020; epub ahead of print
D'Silva A, Captur G, Bhuva AN, Jones S, ... Moon JC, Sharma S
Int J Cardiol: 28 Apr 2020; epub ahead of print | PMID: 32360651
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Abstract

Right Ventricular Global Longitudinal Strain and Outcomes in Heart Failure with Preserved Ejection Fraction.

Lejeune S, Roy C, Ciocea V, Slimani A, ... Gerber BL, Pouleur AC
Background
Right ventricular (RV) strain has emerged as an accurate tool for RV function assessment and is a powerful predictor of survival in patients with heart failure with reduced ejection fraction. However, its prognostic impact in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. The aim of this study was to compare the prognostic value of RV global longitudinal strain (RVGLS) by two-dimensional speckle-tracking echocardiographic (STE) imaging in patients with HFpEF against conventional RV function parameters.
Methods
Patients with HFpEF were prospectively recruited, and 149 of 183 (81%) with analyzable STE RVGLS images constituted the final study population (mean age, 78 ± 9 years; 61% women), compared with 28 control subjects of similar age and sex. All control subjects and 120 patients also underwent cardiac magnetic resonance imaging. Patients were followed up for a primary end point of all-cause mortality and first heart failure hospitalization, and Cox regression analysis was performed.
Results
Mean STE RVGLS was significantly altered in patients with HFpEF compared with control subjects (-21.7 ± 4.9% vs -25.9 ± 4.2%, P < .001). STE RVGLS correlated well with RV ejection fraction by cardiac magnetic resonance (r = -0.617, P < .001). Twenty-eight patients with HFpEF (19%) had impaired STE RVGLS (>-17.5%). During a mean follow-up period of 30 ± 9 months, 91 patients with HFpEF (62%) reached the primary end point. A baseline model was created using independent predictors of the primary end point: New York Heart Association functional class III or IV, hemoglobin level, estimated glomerular filtration rate, and the presence of moderate or severe tricuspid regurgitation. Impaired STE RVGLS provided significant additional prognostic value over this model (χ to enter = 7.85, P = .005). Impaired tricuspid annular plane systolic excursion and fractional area change, however, did not.
Conclusions
In patients with HFpEF, impaired RVGLS has strong prognostic value. STE RVGLS should be considered for systematic evaluation of RV function to identify patients at high risk for adverse events.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 05 May 2020; epub ahead of print
Lejeune S, Roy C, Ciocea V, Slimani A, ... Gerber BL, Pouleur AC
J Am Soc Echocardiogr: 05 May 2020; epub ahead of print | PMID: 32387031
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Impact:
Abstract

Post-dilatation trepidation: Post-dil is \"no big dil\".

Clegg S, Blankenship JC

Selective stent post-dilatation (PD) in a cohort of STEMI patients did not affect major adverse cardiac events but it did decrease device-oriented composite events, a secondary composite end point of less clear significance. This study suggests that selective stent PD in STEMI does not increase the incidence of acute no-reflow or long-term adverse clinical events. In primary PCI for STEMI, if the stent appears under-expanded, then PD, perhaps guided by intravascular imaging (which was not reported in this study), is reasonable.

© 2020 Wiley Periodicals LLC.

Catheter Cardiovasc Interv: 29 May 2020; epub ahead of print
Clegg S, Blankenship JC
Catheter Cardiovasc Interv: 29 May 2020; epub ahead of print | PMID: 32472630
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Impact:
Abstract

Hybrid transvenous lead extraction during cardiac surgery for valvular endocarditis.

Yildirim Y, Petersen J, Tönnis T, Reichenspurner H, Pecha S
Introduction
In patients with endocarditis and cardiac implantable electronic devices (CIED), lead extraction is recommended according to current guidelines. In patients with short lead implant duration, lead extraction by manual traction might be sufficient for intraoperative lead removal. However, in patients with long implant duration, specialized extraction tools like laser- or mechanical rotational sheaths are necessary. We report our experience with transvenous lead extraction, during concomitant cardiac surgery for valvular endocarditis using mechanical rotational sheaths.
Methods and results
Between December 2018 and April 2020, 12 patients were treated with transvenous lead extraction during open-heart surgery using mechanical rotational sheaths. Cardiac surgery was performed due to mitral-, aortic or tricuspid valve endocarditis. All patient-related and procedural data were collected and in-hospital outcome was analyzed retrospectively. Mean patients age was 65.2±16.4 years, 75.0% were male. Nine atrial, 15 ventricular and two coronary sinus leads had to be extracted. The mean time from initial lead implantation was 94.3±39.7 months. Complete procedural- success was achieved in all patients with no major- but one minor complication (pocket hematoma) occurring during lead extraction. Four patients with pacemaker dependency received epicardial leads, seven patients were treated in a two-step approach with endocardial leads while one patients had no further CIED indication. No procedure-related mortality was seen. In-hospital survival was 91.7%.
Conclusions
Valvular endocarditis surgery in combination with lead extraction using mechanical rotational sheaths is safe and feasible. It results in a high procedural success rate with prompt infection control by immediate removal of all infected lead material. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 31 May 2020; epub ahead of print
Yildirim Y, Petersen J, Tönnis T, Reichenspurner H, Pecha S
J Cardiovasc Electrophysiol: 31 May 2020; epub ahead of print | PMID: 32478463
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Abstract

Correlates and Long-Term Implications of Left Ventricular Mechanical Dispersion by Two-Dimensional Speckle-Tracking Echocardiography in Patients with ST-Segment Elevation Myocardial Infarction.

Abou R, Goedemans L, van der Bijl P, Fortuni F, ... Bax JJ, Delgado V
Background
Left ventricular (LV) mechanical dispersion (LVMD), measured with speckle-tracking echocardiography (STE) after ST-segment elevation myocardial infarction (STEMI), has been proposed as a measurement of regional heterogeneity of myocardial contraction and may reflect changes in the myocardial structure (e.g., fibrosis or edema). Further insight into this parameter may aid in the risk stratification of STEMI patients.
Methods
A total of 1,000 STEMI patients (77% male, 60 ± 12 years) treated with primary percutaneous coronary intervention were retrospectively analyzed. The LVMD was assessed with two-dimensional STE within 48 hours following the index infarction. Patients were followed for the occurrence of all-cause mortality.
Results
After a median follow-up of 117 months, 229 (23%) patients died. Nonsurvivors showed worse LV ejection fraction (43% ± 10% vs 48% ± 9%; P < .001) and global longitudinal strain (-12.0% ± 3.5% vs -14.2% ± 3.5%; P = .001) and prolonged LVMD (63 [interquartile range, 50-85] msec vs 52 [interquartile range, 42-63] msec; P < .001) compared with survivors. Increasing age, systolic blood pressure, and heart rate at discharge as well as diabetes mellitus, anterior STEMI, TIMI flow < 2, less usage of angiotensin converter enzyme inhibitors or angiotensin receptor blockers, and impaired LV global longitudinal strain were independently associated with more prolonged LVMD. On multivariable analysis, prolonged LVMD was independently associated with increased risk of all-cause mortality (hazard ratio = 1.012; 95% CI, 1.005-1.018; P = .001) and had incremental value for all-cause mortality over clinical and echocardiographic parameters.
Conclusions
In contemporary STEMI patients, prolonged LVMD was associated with various clinical and echocardiographic parameters. Prolonged LVMD was associated with worse long-term outcome.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 03 May 2020; epub ahead of print
Abou R, Goedemans L, van der Bijl P, Fortuni F, ... Bax JJ, Delgado V
J Am Soc Echocardiogr: 03 May 2020; epub ahead of print | PMID: 32381361
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Impact:
Abstract

Fetal Speckle-Tracking: Impact of Angle of Insonation and Frame Rate on Global Longitudinal Strain.

Semmler J, Day TG, Georgiopoulos G, Garcia-Gonzalez C, ... Charakida M, Simpson JM
Background
There is a growing body of research on fetal speckle-tracking echocardiography because it is considered to be an angle-independent modality. The primary aim of this study was to investigate whether angle of insonation and acquisition frame rate (FR) influence left ventricular endocardial global longitudinal peak strain (GLS) in the fetus.
Methods
Four-chamber views of 122 healthy fetuses were studied at three different angles of insonation (apex up/down, apex oblique, and apex perpendicular) at high and low acoustic FRs. GLS was calculated, and a linear mixed-model analysis was used for analysis. Six hundred fifty-six fetal echocardiographic clips were analyzed (288 in the second trimester, at a median gestation of 21 weeks [interquartile range (IQR), 1 week], and 368 in the third trimester, at a median gestation of 36 weeks [IQR, 2 weeks]).
Results
Angle of insonation and FRs were significant determinants of GLS. Ventricular septum perpendicular to the ultrasound beam was associated with higher (more negative) GLS compared with apex up/down (at high FR: -21.8% vs -19.7%, P < .001; at low FR: -24.1% vs -21.4%, P < .001). Higher frames per second (FPS; median 149 FPS [IQR, 33 FPS] = 61 frames per cycle [FPC] [IQR, 17 FPC]) compared with lower FPS (median 51 FPS [IQR, 15 FPS] = 22 FPC [IQR, 7 FPC]) at the same insonation angle resulted in lower GLS (apex up/down: -19.7% vs -21.4%, P < .001; apex oblique: -21.2% vs -22.7%, P < .001; apex perpendicular: -21.8% vs -24.1%, P < .001).
Conclusions
The present findings show that insonation angle and FR influence GLS significantly. These factors need to be considered when comparing studies with different acquisition protocols, when establishing normative values, and when interpreting pathology. Speckle-tracking echocardiography cannot be considered an angle-independent modality during fetal life.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 14 May 2020; epub ahead of print
Semmler J, Day TG, Georgiopoulos G, Garcia-Gonzalez C, ... Charakida M, Simpson JM
J Am Soc Echocardiogr: 14 May 2020; epub ahead of print | PMID: 32423727
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Impact:
Abstract

Understanding Non-P2 Mitral Regurgitation Using Real-Time Three-Dimensional Transesophageal Echocardiography: Characterization and Factors Leading to Underestimation.

Posada-Martinez EL, Ortiz-Leon XA, Ivey-Miranda JB, Trejo-Paredes MC, ... Arias-Godinez JA, Sugeng L
Background
P2 prolapse is a common cause of degenerative mitral regurgitation (MR); echocardiographic characteristics of non-P2 prolapse are less known. Because of the eccentric nature of degenerative MR jets, the evaluation of MR severity is challenging. The aim of this study was to test the hypotheses that (1) the percentage of severe MR determined by transthoracic echocardiography (TTE) would be lower compared with that determined by transesophageal echocardiography (TEE) in patients with non-P2 prolapse and also in a subgroup with \"horizontal MR\" (a horizontal jet seen on TTE that hugs the leaflets without reaching the atrial wall, particularly found in non-P2 prolapse) and (2) the directions of MR jets between TTE and real-time (RT) three-dimensional (3D) TEE would be discordant.
Methods
One hundred eighteen patients with moderate to severe and severe degenerative MR defined by TEE were studied. The percentage of severe MR between TTE and TEE was compared in P2 and non-P2 prolapse groups and in horizontal and nonhorizontal MR groups. Additionally, differences in the directions of the MR jets between TTE and RT 3D TEE were assessed.
Results
Eighty-six percent of patients had severe MR according to TEE. TTE underestimated severe MR in the non-P2 group (severe MR on TTE, 57%; severe MR on TEE, 85%; P < .001) but not in the P2 group (severe MR on TTE, 79%; severe MR on TEE, 91%; P = .157). Most \"horizontal\" MR jets were found in the non-P2 group (85%), and this subgroup showed even more underestimation of severe MR on TTE (TTE, 22%; TEE, 89%; P < .001). There was discordance in MR jet direction between two-dimensional TTE and RT 3D TEE in 41% of patients.
Conclusions
Non-P2 and \"horizontal\" MR are significantly underestimated on TTE compared with TEE. There is substantial discordance in the direction of the MR jet between RT 3D TEE and TTE. Therefore, TEE should be considered when these subgroups of MR are observed on TTE.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 05 May 2020; epub ahead of print
Posada-Martinez EL, Ortiz-Leon XA, Ivey-Miranda JB, Trejo-Paredes MC, ... Arias-Godinez JA, Sugeng L
J Am Soc Echocardiogr: 05 May 2020; epub ahead of print | PMID: 32387034
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Impact:
Abstract

Magnetic resonance phase contrast velocity mapping for flow quantification in irregular heart rhythms using radial k-space ultrashort echo time imaging.

Hell MM, Francis JM, d\'Arcy J, Robson MD, ... Achenbach S, Myerson SG
Background
Phase contrast velocity mapping sequences utilising ultrashort echo time (UTE) radial k-space sequences have been used to reduce intravoxel dephasing at high velocities. We evaluated the accuracy of the UTE flow sequence for mitral regurgitation (MR) quantification, including patients with atrial fibrillation.
Methods
Forty patients underwent cardiac MRI for indirect MR quantification by assessment of aortic flow using a UTE phase contrast sequence (TE 0.65 ms) combined with left ventricular stroke volume. Retrospective ECG-gating was used in sinus rhythm (30 patients), prospective ECG-triggering in atrial fibrillation (10). MR was also quantified by a standard phase contrast sequence (TE 2.85 ms, standard flow method) and by comparing stroke volumes (volumetric method).
Results
UTE flow-derived MR measurement showed modest agreement in sinus rhythm (95% limits of agreement: ±38.2 ml; ±29.8%) and atrial fibrillation (±33.7 ml; ±30.3%) compared to standard flow assessment. There was little systematic bias in sinus rhythm (mean offset -4.4 ml /-3.5% compared to standard flow assessment), but a slight bias towards greater regurgitation in atrial fibrillation (+15.2 ml /+14.0%). There were wider limits of agreement between the UTE flow method and volumetric method than between the regular flow method and the volumetric method in sinus rhythm (±48.4 ml; ±36.4%; mean offset: -12.2 ml /-9.0%) and similar limits of agreement in atrial fibrillation (±29.6 ml; 25.8%; +12.0 ml /+10.3%).
Conclusions
UTE flow imaging is inferior to conventional flow techniques for MR assessment in patients with sinus rhythm as well as atrial fibrillation. However, the number of atrial fibrillation patients in this initial study is small.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 17 May 2020; epub ahead of print
Hell MM, Francis JM, d'Arcy J, Robson MD, ... Achenbach S, Myerson SG
Int J Cardiol: 17 May 2020; epub ahead of print | PMID: 32439365
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Impact:
Abstract

Aortic Insufficiency during HeartMate 3 Left Ventricular Assist Device Support: AI in HeartMate 3.

Imamura T, Narang N, Kim G, Nitta D, ... Sayer G, Uriel N
Background
Aortic insufficiency (AI) is associated with morbidity and mortality in patients with continuous-flow left ventricular assist devices (LVADs), whereas its impact on the HeartMate 3 LVAD cohorts remains uninvestigated. We aimed to investigate the clinical impact of AI on patients with HeartMate 3 LVADs.
Methods and results
Consecutive 61 patients (median 54 years old and 67% male) implanted with HeartMate 3 LVAD between 2015 and 2019 were enrolled and underwent echocardiography at three months following LVAD implantation. AI severity was quantified by the novel Doppler echocardiographic method obtained at the outflow cannula and the calculated regurgitation fraction ≥30% (moderate or greater) was defined as significant. At 3 months post-implant, 12 (20%) had significant AI. They had a higher incidence of death or heart failure readmissions compared to those without significant AI during a 1-year observational period (70% vs. 24%, p = 0.003) with an adjusted hazard ratio of 2.76 (95% confidence interval 1.03-7.88).
Conclusion
In patients with HeartMate 3 LVAD support, significant AI remains both prevalent and a clinically significant downstream complication.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 26 May 2020; epub ahead of print
Imamura T, Narang N, Kim G, Nitta D, ... Sayer G, Uriel N
J Card Fail: 26 May 2020; epub ahead of print | PMID: 32473380
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Abstract

In Vitro Quantification of Mitral Regurgitation of Complex Geometry by the Modified Proximal Isovelocity Surface Area Method.

Papolla C, Adda J, Rique A, Habib G, Rieu R
Background
Doppler echocardiographic methods, such as the proximal isovelocity surface area (PISA) method, are used to quantify mitral regurgitations (MRs). However, their accuracy and reproducibility are still being discussed, especially in the case of MR of complex geometry. The aim of this study was to evaluate the accuracy of the PISA method depending on the shape and number of regurgitant flows.
Methods
First, various MR shapes and severities (central, oblong, and multiple-jet MR) were mimicked in a left heart simulator. The effective regurgitant orifice area (EROA) was calculated using the standard and modified PISA methods and was compared to a reference value obtained from an electromagnetic flowmeter. Second, in order to clinically validate the in vitro findings, 16 patients were examined with two-dimensional (2D) echocardiography. The results were analyzed by comparing the PISA method and the echocardiographic 2D quantitative volumetric method.
Results
Both hemicylindrical and hemiellipsoidal PISA assumptions improved the quantification of the EROA for oblong MR compared with the traditional PISA method (hemispherical PISA assumption: 11 ± 4.6 mm, P < .01; hemicylindrical PISA assumption: 2 ± 0.8 mm, P = .83; hemiellipsoidal PISA assumption: 6 ± 3.7 mm, P = .05). In the case of multiple jets of different sizes, an improved EROA calculation was measured when both jets were considered (single hemispherical PISA assumption: 4.5 ± 0.7 mm, P < .01; double hemispherical PISA assumption: 2 ± 1.1 mm, P = .64).
Conclusion
For a correct diagnosis of MR, the PISA geometry must be considered. A measurement of both PISA radius and PISA width is necessary for an accurate quantification of an oblong MR. In the case of a double-jet MR, a measurement of the two radii is recommended.

Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 13 May 2020; epub ahead of print
Papolla C, Adda J, Rique A, Habib G, Rieu R
J Am Soc Echocardiogr: 13 May 2020; epub ahead of print | PMID: 32418654
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Abstract

Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing.

Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, ... Mendell JR, Hor KN
Background
Varied detection methods have resulted in conflicting reports on the prevalence of cardiac disease in Duchenne and Becker muscular dystrophy carriers (MDC).
Methods
We performed a prospective cohort study of 77 genetically-confirmed MDC mothers, 22 non-carrier mothers, and 25 controls. All participants underwent Cardiopulmonary Exercise Testing (CPET) and Cardiac Magnetic Resonance imaging (CMR).
Results
25% of carriers had ventricular ectopy in recovery of exercise (RecVE) as compared to 1 non-carrier and no controls (p = .003). No difference in age or maximal oxygen consumption was noted. 11 carriers had abnormal (<55%) left ventricular ejection fraction by CMR. Evidence of late gadolinium enhancement (LGE) was noted in 48% of MDC, 1 non-carrier patient and no control subjects (p < .0001). Subset analysis of LGE+ and LGE- subjects revealed differences in age (44.1 v 38.6 yrs.; p = .005), presence of RecVE, (38.9% v 10.5%, p = .004), and high serum creatine kinase (CK) (> 289 U/L; 52.8% v 31.6%, p = .065).
Conclusion
We describe the prevalence of disease using CPET and CMR in genetically-proven MDC. 49% of carriers had fibrosis, opposed to 5% of non-carriers, highlighting the importance of genetic testing in this population. Despite cardiomyopathy, functional assessment by treadmill was normal, illustrating the discrepancy in cardiac and skeletal muscle impacts. Age, RecVE and serum CK appear to have an important role in predicting cardiomyopathy. Serum CK levels suggest that a systemic higher global disease severity and not tissue heterogeneity may be the etiology for greater cardiac disease and relatively spared skeletal muscle disease in this population. Clinical Trial registration https://clinicaltrials.gov/ct2/show/NCT02972580?term=mendell&cond=Duchenne+Muscular+Dystrophy&rank=5; ClinicalTrials.gov Identifier: NCT02972580.

Copyright © 2020. Published by Elsevier B.V.

Int J Cardiol: 26 May 2020; epub ahead of print
Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, ... Mendell JR, Hor KN
Int J Cardiol: 26 May 2020; epub ahead of print | PMID: 32473283
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