Topic: Imaging

Abstract

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

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

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

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

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis.

Lee SP, Suh HY, Park S, Oh S, ... Paeng JC, Sohn DW
Background
It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.
Objectives
The purpose of this study was to demonstrate that C-Pittsburgh B compound positron emission tomography (C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.
Methods
This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.
Results
The degree of myocardial C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).
Conclusions
These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.

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

J Am Coll Cardiol: 03 Feb 2020; 75:380-390
Lee SP, Suh HY, Park S, Oh S, ... Paeng JC, Sohn DW
J Am Coll Cardiol: 03 Feb 2020; 75:380-390 | PMID: 32000949
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Abstract

A Contemporary Picture of Enterococcal Endocarditis.

Pericàs JM, Llopis J, Muñoz P, Gálvez-Acebal J, ... Miró JM,
Background
Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking.
Objectives
The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort.
Methods
This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses.
Results
Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse.
Conclusions
Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

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

J Am Coll Cardiol: 10 Feb 2020; 75:482-494
Pericàs JM, Llopis J, Muñoz P, Gálvez-Acebal J, ... Miró JM,
J Am Coll Cardiol: 10 Feb 2020; 75:482-494 | PMID: 32029130
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Abstract

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

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

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

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

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

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

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

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

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

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

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

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



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

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

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

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



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

Aetiology and outcomes of severe right ventricular dysfunction.

Padang R, Chandrashekar N, Indrabhinduwat M, Scott CG, ... Pellikka PA, Kane GC
Aims
Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD.
Methods and results
Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58-64%] and 35% (95% CI 31-38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57-65%) and 33% (95% CI 28-37%), respectively; vs. 76% (95% CI 68-82%) and 50% (95% CI 40-59%) in PAH, vs. 71% (95% CI 64-76%) and 49% (95% CI 41-58%) in thromboembolic diseases, vs. 42% (95% CI 35-49%) and 8% (95% CI 4-15%) in CLD (log-rank P < 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD.
Conclusion
One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.

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: 10 Feb 2020; epub ahead of print
Padang R, Chandrashekar N, Indrabhinduwat M, Scott CG, ... Pellikka PA, Kane GC
Eur Heart J: 10 Feb 2020; epub ahead of print | PMID: 32047900
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Abstract

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

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

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



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

2020 Focused Update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation.

Bonow RO, O\'Gara PT, Adams DH, Badhwar V, ... Whisenant B, Woo YJ

Mitral regurgitation (MR) is a complex valve lesion that can pose significant management challenges. This Expert Consensus Decision Pathway emphasizes that recognition of MR should prompt an assessment of its etiology, mechanism, and severity, as well as consideration of the indications for treatment. The document is a focused update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation, with some sections updated and others added in light of the publication of new trial data related to secondary MR, among other developments. A structured approach to evaluation based on clinical findings, accurate echocardiographic imaging, and, when necessary, adjunctive testing, can help clarify decision making. Treatment goals include timely intervention by an experienced multidisciplinary heart team to prevent left ventricular dysfunction, heart failure, reduced quality of life, and premature death.

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

J Am Coll Cardiol: 09 Feb 2020; epub ahead of print
Bonow RO, O'Gara PT, Adams DH, Badhwar V, ... Whisenant B, Woo YJ
J Am Coll Cardiol: 09 Feb 2020; epub ahead of print | PMID: 32068084
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Abstract

Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction.

Cremer S, Schloss MJ, Vinegoni C, Foy BH, ... Swirski FK, Nahrendorf M
Background
Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism\'s response to secondary inflammatory challenges.
Objectives
This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation.
Methods
The investigators developed a surgical mouse model in which 2 subsequent MIs affected different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex artery followed by the left anterior descending coronary artery branch. The study characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac magnetic resonance imaging.
Results
A first MI-induced bone marrow \"memory\" via a circulating signal, reducing hematopoietic maintenance factor expression in bone marrow macrophages. This dampened the organism\'s reaction to subsequent events. Despite a similar extent of injury according to troponin levels, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. The increase of white blood count in 28 patients was lower after recurrent MI compared with their first MI.
Conclusions
The data suggested that hematopoietic and innate immune responses are shaped by a preceding MI.

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

J Am Coll Cardiol: 02 Mar 2020; 75:901-915
Cremer S, Schloss MJ, Vinegoni C, Foy BH, ... Swirski FK, Nahrendorf M
J Am Coll Cardiol: 02 Mar 2020; 75:901-915 | PMID: 32130926
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Abstract

Emerging Techniques for Risk Stratification in Nonischemic Dilated Cardiomyopathy: JACC Review Topic of the Week.

Marrow BA, Cook SA, Prasad SK, McCann GP

Dilated cardiomyopathy (DCM) is a common condition, which carries significant mortality from sudden cardiac death and pump failure. Left ventricular ejection fraction has conventionally been used as a risk marker for sudden cardiac death, but has performed poorly in trials. There have been significant advances in the areas of cardiac magnetic resonance imaging and genetics, which are able to provide useful rick prediction in DCM. Biomarkers and cardiopulmonary exercise testing are well validated in the prediction of risk in heart failure; however, they have been tested less specifically in the DCM setting. This review will discuss these methods with a view toward multiparametric risk assessment in DCM with the hope of creating parametric risk models to predict sudden cardiac death and pump failure in the DCM population.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 16 Mar 2020; 75:1196-1207
Marrow BA, Cook SA, Prasad SK, McCann GP
J Am Coll Cardiol: 16 Mar 2020; 75:1196-1207 | PMID: 32164893
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Abstract

Early Diagnosis of Myocardial Infarction With Point-of-Care High-Sensitivity Cardiac Troponin I.

Boeddinghaus J, Nestelberger T, Koechlin L, Wussler D, ... Mueller C,
Background
Until now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms.
Objectives
This study aimed to assess the clinical performance of a point-of-care (POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI).
Methods
This study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue-specific 0/1-h algorithm.
Results
MI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval [CI]: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p < 0.001). A single cutoff concentration <3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration >60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication.
Conclusions
The POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study [APACE]; NCT00470587).

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Mar 2020; 75:1111-1124
Boeddinghaus J, Nestelberger T, Koechlin L, Wussler D, ... Mueller C,
J Am Coll Cardiol: 16 Mar 2020; 75:1111-1124 | PMID: 32164884
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Abstract

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

Muresan ID, Agoston-Coldea L, Dumitrascu DL

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

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

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

Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients.

Marfella R, Amarelli C, Cacciatore F, Balestrieri ML, ... Paolisso G, Napoli C
Background
Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood.
Objectives
By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup.
Methods
The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase-polymerase chain reaction.
Results
There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p < 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors.
Conclusions
Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 23 Mar 2020; 75:1249-1262
Marfella R, Amarelli C, Cacciatore F, Balestrieri ML, ... Paolisso G, Napoli C
J Am Coll Cardiol: 23 Mar 2020; 75:1249-1262 | PMID: 32192650
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Abstract

Integrin β1D Deficiency-Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in ARVC.

Wang Y, Li C, Shi L, Chen X, ... Song LS, Zhao S

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias and increased risk of sudden cardiac death (SCD). The guideline for management of ARVC patients is to improve quality of life by reducing arrhythmic symptoms and to prevent SCD. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood.Using protein mass spectrometry analyses, we identified integrin β1 is down-regulated in ARVC hearts without changes to Ca-handling proteins. As adult cardiomyocytes express only the β1D isoform, we generated a cardiac specific β1D knockout (β1D) mouse model, and performed functional imaging and biochemical analyses to determine the consequences from integrin β1D loss of function in the heart in vivo and in vitro.Integrin β1D deficiency and RyR2 Ser-2030 hyper-phosphorylation were detected by western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found purified integrin β1D protein could stabilize RyR2 function by decreasing RyR2 open probability (Po), mean open time (To), and increasing mean close time (Tc). β1D mice exhibited normal cardiac function and morphology, but presented with catecholaminesensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca handling in β1D cardiomyocytes. Mechanistically, we revealed that loss of desmoplakin induces integrin β1D deficiency in ARVC mediated through an ERK1/2 - fibronectin - ubiquitin/lysosome pathway.Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.



Circulation: 02 Mar 2020; epub ahead of print
Wang Y, Li C, Shi L, Chen X, ... Song LS, Zhao S
Circulation: 02 Mar 2020; epub ahead of print | PMID: 32122157
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Abstract

Preventing Complications in Pregnant Women With Cardiac Disease.

Pfaller B, Sathananthan G, Grewal J, Mason J, ... Siu SC, Silversides CK
Background
Pregnancy can lead to complications in women with heart disease, and these complications can be life threatening. Understanding serious complications and how they can be prevented is important.
Objectives
The primary objectives were to determine the incidence of serious cardiac events (SCEs) in pregnant women with heart disease, whether they were preventable, and their impact on fetal and neonatal outcomes. Serious obstetric events were also examined.
Methods
A prospectively assembled cohort of 1,315 pregnancies in women with heart disease was studied. SCEs included cardiac death or arrest, ventricular arrhythmias, congestive heart failure or arrhythmias requiring admission to an intensive care unit, myocardial infarction, stroke, aortic dissection, valve thrombosis, endocarditis, and urgent cardiac intervention. The Harvard Medical Study criteria were used to adjudicate preventability.
Results
Overall, 3.6% of pregnancies (47 of 1,315) were complicated by SCEs. The most frequent SCEs were cardiac death or arrest, heart failure, arrhythmias, and urgent interventions. Most SCEs (66%) occurred in the antepartum period. Almost one-half of SCEs (49%) were preventable; the majority of preventable SCEs (74%) were secondary to provider management factors. Adverse fetal and neonatal events were more common in pregnancies with SCEs compared with those without cardiac events (62% vs. 29%; p < 0.001). Serious obstetric events were less common (1.7%) and were primarily due to pre-eclampsia with severe features.
Conclusions
Pregnant women with heart disease are at risk for serious cardiac complications, and approximately one-half of all SCEs are preventable. Strategies to prevent serious cardiac complications in this high-risk cohort of women need to be developed.

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

J Am Coll Cardiol: 30 Mar 2020; 75:1443-1452
Pfaller B, Sathananthan G, Grewal J, Mason J, ... Siu SC, Silversides CK
J Am Coll Cardiol: 30 Mar 2020; 75:1443-1452 | PMID: 32216913
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Abstract

Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time.

McCartney PJ, Maznyczka AM, Eteiba H, McEntegart M, ... Berry C,
Background
Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.
Objectives
This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.
Methods
This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).
Results
Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).
Conclusion
In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294).

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 30 Mar 2020; 75:1406-1421
McCartney PJ, Maznyczka AM, Eteiba H, McEntegart M, ... Berry C,
J Am Coll Cardiol: 30 Mar 2020; 75:1406-1421 | PMID: 32216909
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Abstract

2-Year Outcomes After Stenting of Lipid-Rich and Nonrich Coronary Plaques.

Yamamoto MH, Maehara A, Stone GW, Kini AS, ... Muller JE, Weisz G
Background
Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes.
Objectives
The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents.
Methods
In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate.
Results
Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI (hazard ratio of maxLCBI per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors.
Conclusions
Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid.

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

J Am Coll Cardiol: 30 Mar 2020; 75:1371-1382
Yamamoto MH, Maehara A, Stone GW, Kini AS, ... Muller JE, Weisz G
J Am Coll Cardiol: 30 Mar 2020; 75:1371-1382 | PMID: 32216905
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Abstract

Changes in Stroke Volume After Renal Denervation: Insight From Cardiac Magnetic Resonance Imaging.

Lurz P, Kresoja KP, Rommel KP, von Roeder M, ... Desch S, Fengler K

Recent trial results support catheter-based renal denervation (RDN) for treatment of hypertension, while the exact mechanisms causing blood pressure to fall remain incompletely understood. Cardiac magnetic resonance imaging was used to assess the effects of RDN on cardiac function in patients with hypertension undergoing RDN and compared with sham treatment. Cardiac magnetic resonance imaging was used to assess stroke volume index, cardiac index, heart rate, systemic vascular resistance index, and stroke work index from aortic flow measurements. Patients with resistant hypertension from a randomized, sham-controlled RDN trial underwent cardiac magnetic resonance imaging before RDN and at follow-up (randomized cohort). Results were then validated in a cohort of patients with resistant hypertension undergoing RDN and cardiac magnetic resonance imaging (validation cohort). In total, 162 patients were included 52 patients in the randomized trial (27 shams) and 110 patients in the validation cohort. In the randomized cohort, stroke volume index was reduced by 4.7±9.8 mL/m in the RDN cohort and remained unchanged in the sham cohort (=0.008 for between-group comparison), while cardiac index and stroke work index tended to be reduced in RDN patients but not in sham patients (-0.10±5.9 versus 0.17±0.51 L/min per m and -7.1±12.5 versus -1.4±10.4 g/m, =0.08 for both). In contrast, systemic vascular resistance index and heart rate remained unchanged after RDN. In the validation cohort, reduction of stroke volume index was confirmed, and cardiac index and stroke work index were also reduced significantly, whereas systemic vascular resistance index and heart rate remained unchanged at follow-up. In this study of patients with resistant hypertension, RDN resulted in a reduction of stroke volume when compared with sham.



Hypertension: 02 Feb 2020:HYPERTENSIONAHA11914310; epub ahead of print
Lurz P, Kresoja KP, Rommel KP, von Roeder M, ... Desch S, Fengler K
Hypertension: 02 Feb 2020:HYPERTENSIONAHA11914310; epub ahead of print | PMID: 32008429
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Abstract

Cardiomyopathy associated with the Ala143Thr variant of the gene.

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

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

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

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

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

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



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

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

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

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

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

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

Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry.

Marstrand P, Han L, Day SM, Olivotto I, ... Ho CY,

The terminology \"end-stage\" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (herein referred to as HCM-LVSD), defined when left ventricular ejection fraction (LVEF) <50% is present. The prognosis of HCM-LVSD has reportedly been poor, but due to its relative rarity, natural history remains incompletely characterized.Data from eleven high-volume HCM specialty centers comprising the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development.From a cohort of 6,793 HCM patients, 553 (8%) met criteria for HCM-LVSD. Overall, 75% of HCM-LVSD patients experienced clinically relevant events and 35% met the composite outcome (all-cause death (n=128), cardiac transplantation (n=55) or left ventricular assist device implantation (n=9). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (Hazard Ratio (HR) 5.6 [95% Confidence Interval 2.3-13.5]), atrial fibrillation (HR 2.6 [1.7, 3.5]), LVEF <35% (HR 2.0 [1.3, 2.8]). The incidence of new HCM-LVSD was ~7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater LV cavity size (HR 1.1 [1.0-1.3] and wall thickness (HR 1.3 [1.1, 1.4]), LVEF 50-60% (HR 1.8 [1.2, 2.8]-2.8 [1.8, 4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR 2.3 [1.0, 4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR 1.5 [1.0, 2.1] and 2.5 [1.2, 5.1], respectively).HCM-LVSD affects approximately 8% of HCM patients. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death-equivalent with an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and in the risk for incident development of HCM-LVSD (thin filament variants).



Circulation: 30 Mar 2020; epub ahead of print
Marstrand P, Han L, Day SM, Olivotto I, ... Ho CY,
Circulation: 30 Mar 2020; epub ahead of print | PMID: 32228044
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Abstract

Effects of Chronic Nicotine Inhalation on Systemic and Pulmonary Blood Pressure and Right Ventricular Remodeling in Mice.

Oakes JM, Xu J, Morris TM, Fried ND, ... Gardner JD, Yue X

Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.



Hypertension: 15 Mar 2020:HYPERTENSIONAHA11914608; epub ahead of print
Oakes JM, Xu J, Morris TM, Fried ND, ... Gardner JD, Yue X
Hypertension: 15 Mar 2020:HYPERTENSIONAHA11914608; epub ahead of print | PMID: 32172623
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Abstract

Infective endocarditis complicating transcatheter aortic valve implantation.

Harding D, Cahill TJ, Redwood SR, Prendergast BD

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

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

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

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

Ramchand J, Fava AM, Chetrit M, Desai MY

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

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

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

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

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

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



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

Exercise and myocardial injury in hypertrophic cardiomyopathy.

Cramer GE, Gommans DHF, Dieker HJ, Michels M, ... Kofflard M, Brouwer M
Objective
Troponin and high signal intensity on T2-weighted (HighT2) cardiovascular magnetic resonance imaging (CMRi) are both markers of myocardial injury in hypertrophic cardiomyopathy (HCM). The interplay between exercise and disease development remains uncertain in HCM. We sought to assess the occurrence of postexercise troponin rises and its determinants.
Methods
Multicentre project on patients with HCM and mutation carriers without hypertrophy (controls). Participants performed a symptom limited bicycle test with hs-cTnT assessment pre-exercise and 6 hours postexercise. Pre-exercise CMRi was performed in patients with HCM to assess measures of hypertrophy and myocardial injury. Depending on baseline troponin (< or 13 ng/L), a rise was defined as a >50% or >20% increase, respectively.
Results
Troponin rises occurred in 18% (23/127) of patients with HCM and 4% (2/53) in mutation carriers (p=0.01). Comparing patients with HCM with and without a postexercise troponin rise, maximum heart rates (157±19 vs 143±23, p=0.004) and maximal wall thickness (20 mm vs 17 mm, p=0.023) were higher in the former, as was the presence of late gadolinium enhancement (85% vs 57%, p=0.02). HighT2 was seen in 65% (13/20) and 19% (15/79), respectively (p<0.001). HighT2 was the only independent predictor of troponin rise (adjusted odds ratio 7.9; 95% CI 2.7 to 23.3; p<0.001).
Conclusions
Postexercise troponin rises were seen in about 20% of patients with HCM, almost five times more frequent than in mutation carriers. HighT2 on CMRi may identify a group of particularly vulnerable patients, supporting the concept that HighT2 reflects an active disease state, prone to additional injury after a short episode of high oxygen demand.

© 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: 29 Jan 2020; epub ahead of print
Cramer GE, Gommans DHF, Dieker HJ, Michels M, ... Kofflard M, Brouwer M
Heart: 29 Jan 2020; epub ahead of print | PMID: 32001622
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Abstract

Sex Differences in Non-Obstructive Coronary Artery Disease.

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

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

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

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

Coagulation: at the heart of infective endocarditis.

Liesenborghs L, Meyers S, Vanassche T, Verhamme P

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

© 2020 International Society on Thrombosis and Haemostasis.

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

Compartmentalized β1-Adrenergic Signaling Synchronizes Excitation-contraction Coupling Without Modulating Individual Ca2+ Sparks in Healthy and Hypertrophied Cardiomyocytes.

Yang HQ, Zhou P, Wang LP, Zhao YT, ... Xu M, Wang SQ
Aims
β-Adrenergic receptors (βARs) play pivotal roles in regulating cardiac excitation-contraction (E-C) coupling. Global signaling of β1ARs upregulates both the influx of Ca2+ through sarcolemmal L-type Ca2+ channels (LCCs) and the release of Ca2+ from the sarcoplasmic reticulum (SR) through the ryanodine receptors (RyRs). However, we recently found that β2AR stimulation meditates \"offside compartmentalization\", confining β1AR signaling into subsarcolemmal nanodomains without reaching SR proteins. In the present study, we aim to investigate the new question whether and how compartmentalized β1AR signaling regulates cardiac E-C coupling.
Methods and results
By combining confocal Ca2+ imaging and patch clamp techniques, we investigated the effects of compartmentalized βAR signaling on E-C coupling at both cellular and molecular levels. We found that simultaneous activation of β2 and β1ARs, in contrast to global signaling of β1ARs, modulated neither the amplitude and spatiotemporal properties of Ca2+ sparks nor the kinetics of the RyR response to LCC Ca2+ sparklets. Nevertheless, by upregulating LCC current, compartmentalized β1AR signaling synchronized RyR Ca2+ release and increased the functional reserve (stability margin) of E-C coupling. In circumstances of briefer excitation durations or lower RyR responsivity, compartmentalized βAR signaling, by increasing the intensity of Ca2+ triggers, helped stabilize the performance of E-C coupling and enhanced the Ca2+ transient amplitude in failing heart cells.
Conclusion
Given that compartmentalized βAR signaling can be induced by stress-associated levels of catecholamines, our results revealed an important, yet unappreciated, heart regulation mechanism that is autoadaptive to varied stress conditions.

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

Cardiovasc Res: 06 Feb 2020; epub ahead of print
Yang HQ, Zhou P, Wang LP, Zhao YT, ... Xu M, Wang SQ
Cardiovasc Res: 06 Feb 2020; epub ahead of print | PMID: 32031586
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Abstract

Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial.

Corcoran D, Radjenovic A, Mordi IR, Nazir SA, ... Squire I, Berry C
Aims
The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD).
Methods and results
In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of -9.6 mmHg (P = 0.01) and -13.5 mmHg (P = 0.0003) for systolic blood pressure and -5.2 mmHg (P = 0.02) and -8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (-0.24 vs. -0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up.
Conclusion
In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.

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

Cardiovasc Res: 16 Feb 2020; epub ahead of print
Corcoran D, Radjenovic A, Mordi IR, Nazir SA, ... Squire I, Berry C
Cardiovasc Res: 16 Feb 2020; epub ahead of print | PMID: 32065620
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Abstract

Nfatc1 Promotes Interstitial Cell Formation During Cardiac Valve Development in Zebrafish.

Gunawan F, Gentile A, Gauvrit S, Stainier D, Bensimon-Brito A

The transcription factor NFATC1 has been implicated in cardiac valve formation in humans and mice, but we know little about the underlying mechanisms. To gain mechanistic understanding of cardiac valve formation at single cell resolution and insights into the role of NFATC1 in this process, we used the zebrafish model as it offers unique attributes for live imaging and facile genetics.To understand the role of Nfatc1 in cardiac valve formation.Using the zebrafish atrioventricular (AV) valve, we focus on the valve interstitial cells (VICs) which confer biomechanical strength to the cardiac valve leaflets. We find that initially AV endocardial cells (ECs) migrate collectively into the cardiac jelly to form a bilayered structure; subsequently, the cells that led this migration invade the extracellular matrix (ECM) between the two EC monolayers, undergo endothelial-to-mesenchymal transition as marked by loss of intercellular adhesion, and differentiate into VICs. These cells proliferate and are joined by a few neural crest-derived cells. VIC expansion as well as a switch from a pro-migratory to an elastic ECM drive valve leaflet elongation. Functional analysis of Nfatc1 reveals its requirement during VIC development. Zebrafish nfatc1 mutants form significantly fewer VICs due to reduced proliferation and impaired recruitment of endocardial and neural crest cells during the early stages of VIC development. With high-speed microscopy and echocardiography, we show that reduced VIC formation correlates with valvular dysfunction and severe retrograde blood flow that persist into adulthood. Analysis of downstream effectors reveals that Nfatc1 promotes the expression of twist1b, a well-known regulator of epithelial-to-mesenchymal transition.Our study sheds light on the function of Nfatc1 in zebrafish cardiac valve development and reveals its role in VIC formation. It also further establishes the zebrafish as a powerful model to carry out longitudinal studies of valve formation and function.



Circ Res: 17 Feb 2020; epub ahead of print
Gunawan F, Gentile A, Gauvrit S, Stainier D, Bensimon-Brito A
Circ Res: 17 Feb 2020; epub ahead of print | PMID: 32070236
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Abstract

Effects of third-generation β-blockers, atenolol or amlodipine on blood pressure variability and target organ damage in spontaneously hypertensive rats.

Del Mauro JS, Prince PD, Allo MA, Santander Plantamura Y, ... Donato M, Höcht C
Background
β-blockers are no longer considered as first-line antihypertensive drugs due to their lower cardioprotection.
Method
Considering the differences in the pharmacological properties of β-blockers, the present work compared the effects of third-generation β-blockers - carvedilol and nebivolol - with a first-line agent - amlodipine - on hemodynamic parameters, including short-term blood pressure variability (BPV), and their ability to prevent target organ damage in spontaneously hypertensive rats (SHR). SHR rats were orally treated with carvedilol, nebivolol, atenolol, amlodipine or vehicle for 8 weeks. Wistar Kyoto rats treated with vehicle were used as normotensive group. Echocardiographic evaluation, BP, and short-term BPV measurements were performed. Left ventricle and thoracic aorta were removed for histological evaluations and to assess the expression of transforming growth factor β (TGF-β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).
Results
Carvedilol, nebivolol or amlodipine induced a greater reduction of carotid BP, short-term BPV and echocardiography parameters than atenolol in SHR rats. Carvedilol, nebivolol and amlodipine were more effective than atenolol in the prevention of cardiac hypertrophy, and cardiac and aortic collagen deposit. Carvedilol and nebivolol, but not atenolol, reduced the expressions of fibrotic and inflammatory biomarkers - TGF-β, TNF-α and IL-6 - in SHR rats to a similar extent to that of amlodipine.
Conclusion
Chronic treatment with carvedilol or nebivolol attenuates carotid BP and short-term BPV, and reduces target organ damage in SHR to a greater extent than atenolol. Our findings suggest that the lower cardiovascular protection of nonvasodilating β-blockers, as atenolol, in hypertension must not be translated to third-generation β-blockers.



J Hypertens: 28 Feb 2020; 38:536-545
Del Mauro JS, Prince PD, Allo MA, Santander Plantamura Y, ... Donato M, Höcht C
J Hypertens: 28 Feb 2020; 38:536-545 | PMID: 32028517
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Abstract

Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity.

Lambert J, Lamacie M, Thampinathan B, Altaha MA, ... Wintersperger BJ, Thavendiranathan P
Objectives
To compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD).
Methods
We prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM.
Results
Patients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities.
Conclusion
Temporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.

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

Heart: 24 Feb 2020; epub ahead of print
Lambert J, Lamacie M, Thampinathan B, Altaha MA, ... Wintersperger BJ, Thavendiranathan P
Heart: 24 Feb 2020; epub ahead of print | PMID: 32098808
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Abstract

Whole-Body Atherosclerosis Imaging by Positron Emission Tomography/Magnetic Resonance Imaging: From Mice to Nonhuman Primates.

Calcagno C, Pérez-Medina C, Mulder WJM, Fayad ZA

Cardiovascular disease due to atherosclerosis is still the main cause of morbidity and mortality worldwide. This disease is a complex systemic disorder arising from a network of pathological processes within the arterial vessel wall, and, outside of the vasculature, in the hematopoietic system and organs involved in metabolism. Recent years have seen tremendous efforts in the development and validation of quantitative imaging technologies for the noninvasive evaluation of patients with atherosclerotic cardiovascular disease. Specifically, the advent of combined positron emission tomography and magnetic resonance imaging scanners has opened new exciting opportunities in cardiovascular imaging. In this review, we will describe how combined positron emission tomography/magnetic resonance imaging scanners can be leveraged to evaluate atherosclerotic cardiovascular disease at the whole-body level, with specific focus on preclinical animal models of disease, from mouse to nonhuman primates. We will broadly describe 3 major areas of application: (1) vascular imaging, for advanced atherosclerotic plaque phenotyping and evaluation of novel imaging tracers or therapeutic interventions; (2) assessment of the ischemic heart and brain; and (3) whole-body imaging of the hematopoietic system. Finally, we will provide insights on potential novel technical developments which may further increase the relevance of integrated positron emission tomography/magnetic resonance imaging in preclinical atherosclerosis studies.



Arterioscler Thromb Vasc Biol: 01 Apr 2020:ATVBAHA119313629; epub ahead of print
Calcagno C, Pérez-Medina C, Mulder WJM, Fayad ZA
Arterioscler Thromb Vasc Biol: 01 Apr 2020:ATVBAHA119313629; epub ahead of print | PMID: 32237905
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Abstract

Artificial intelligence in medical imaging: A radiomic guide to precision phenotyping of cardiovascular disease.

Oikonomou EK, Siddique M, Antoniades C

Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.

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

Cardiovasc Res: 23 Feb 2020; epub ahead of print
Oikonomou EK, Siddique M, Antoniades C
Cardiovasc Res: 23 Feb 2020; epub ahead of print | PMID: 32090243
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Abstract

Transcatheter treatment of postinfarct ventricular septal defects.

Giblett JP, Jenkins DP, Calvert PA

Postinfarct ventricular septal defects (VSDs) are a mechanical complication of acute myocardial infarction (AMI) with a very poor prognosis. They are estimated to occur in 0.2% of patients presenting with AMI, with 1-month survival of 6% without intervention. Guidelines recommend surgical repair, but recent advances in transcatheter technology, and bespoke device development, mean it is increasingly viable as a closure option. Surgical mortality is between 30% and 50% for all-comers, while in series of transcatheter closure, mortality was 32%. Transcatheter closure appears durable, with no evidence of late leaks and low long-term mortality in series with up to 5-year follow-up. Guidelines recommend early closure, which is likely to provide most benefit for patients regardless of the closure method. Multimodality cardiac imaging including echocardiography, CT and cardiac MRI can define size, shape, location of defects and their relationship to other cardiac structures, assisting with treatment decisions. Brief delay to allow stabilisation of the patient is appropriate, but untreated patients risk rapid deterioration. Mechanical circulatory support may be helpful, although the preferred modality is unclear. Transcatheter closure involves large bore venous access and the formation of an arteriovenous loop (under fluoroscopic and trans-oesophageal echocardiographic guidance) in order to facilitate deployment of the device in the defect and close the postinfarct VSD. Guidelines suggest transcatheter closure as an alternative to surgical repair in centres where appropriate expertise exists, but decisions for all patients with postinfarct VSD should be led by the multidisciplinary heart team.

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

Heart: 27 Feb 2020; epub ahead of print
Giblett JP, Jenkins DP, Calvert PA
Heart: 27 Feb 2020; epub ahead of print | PMID: 32111641
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Abstract

Multimodality imaging in patients with post-cardiac injury syndrome.

Verma BR, Chetrit M, Gentry Iii JL, Noll A, ... Jellis C, Klein AL

This review article is focused on the role of echocardiography, cardiac CT and cardiac magnetic resonance (CMR) imaging in diagnosing and managing patients with post-cardiac injury syndrome (PCIS). Clinically, the spectrum of pericardial diseases under PCIS varies not only in form and severity of presentation but also in the timing varying from weeks to months, thus making it difficult to diagnose. Pericarditis developing after recent or remote myocardial infarction, cardiac surgery or ablation if left untreated or under-treated could worsen into complicated pericarditis which can lead to decreased quality of life and increased morbidity. Colchicine in combination with other anti-inflammatory agents (non-steroidal anti-inflammatory drugs) is proven to prevent and treat acute pericarditis as well as its relapses under various scenarios. Imaging modalities such as echocardiography, CT and CMR play a pivotal role in diagnosing PCIS especially in difficult cases or when clinical suspicion is low. Echocardiography is the tool of choice for emergent bedside evaluation for cardiac tamponade and to electively study the haemodynamics impact of constrictive pericarditis. CT can provide information on pericardial thickening, calcification, effusions and lead perforations. CMR can provide pericardial tissue characterisation, haemodynamics changes and guide long-term treatment course with anti-inflammatory agents. It is important to be familiar with the indications as well as findings from these multimodality imaging tools for clinical decision-making.

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

Heart: 10 Mar 2020; epub ahead of print
Verma BR, Chetrit M, Gentry Iii JL, Noll A, ... Jellis C, Klein AL
Heart: 10 Mar 2020; epub ahead of print | PMID: 32161040
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Abstract

Prediction of prognosis in patients with tetralogy of Fallot based on deep learning imaging analysis.

Diller GP, Orwat S, Vahle J, Bauer UMM, ... Baumgartner H,
Objective
To assess the utility of machine learning algorithms for automatically estimating prognosis in patients with repaired tetralogy of Fallot (ToF) using cardiac magnetic resonance (CMR).
Methods
We included 372 patients with ToF who had undergone CMR imaging as part of a nationwide prospective study. Cine loops were retrieved and subjected to automatic deep learning (DL)-based image analysis, trained on independent, local CMR data, to derive measures of cardiac dimensions and function. This information was combined with established clinical parameters and ECG markers of prognosis.
Results
Over a median follow-up period of 10 years, 23 patients experienced an endpoint of death/aborted cardiac arrest or documented ventricular tachycardia (defined as >3 documented consecutive ventricular beats). On univariate Cox analysis, various DL parameters, including right atrial median area (HR 1.11/cm², p=0.003) and right ventricular long-axis strain (HR 0.80/%, p=0.009) emerged as significant predictors of outcome. DL parameters were related to adverse outcome independently of left and right ventricular ejection fraction and peak oxygen uptake (p<0.05 for all). A composite score of enlarged right atrial area and depressed right ventricular longitudinal function identified a ToF subgroup at significantly increased risk of adverse outcome (HR 2.1/unit, p=0.007).
Conclusions
We present data on the utility of machine learning algorithms trained on external imaging datasets to automatically estimate prognosis in patients with ToF. Due to the automated analysis process these two-dimensional-based algorithms may serve as surrogates for labour-intensive manually attained imaging parameters in patients with ToF.

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

Heart: 10 Mar 2020; epub ahead of print
Diller GP, Orwat S, Vahle J, Bauer UMM, ... Baumgartner H,
Heart: 10 Mar 2020; epub ahead of print | PMID: 32161041
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Abstract

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

Roberts WC, Roberts CS, Kale I

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

Copyright © 2019 Elsevier Inc. All rights reserved.

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

Role of advanced left ventricular imaging in adults with aortic stenosis.

Calin A, Mateescu AD, Popescu AC, Bing R, Dweck MR, Popescu BA

This review focuses on the available data regarding the utility of advanced left ventricular (LV) imaging in aortic stenosis (AS) and its potential impact for optimising the timing of aortic valve replacement. Ejection fraction is currently the only LV parameter recommended to guide intervention in AS. The cut-off value of 50%, recommended for decision-making in asymptomatic patients with AS, is currently under debate. Several imaging parameters have emerged as predictors of disease progression and clinical outcomes in this setting. Global longitudinal LV strain by speckle tracking echocardiography is useful for risk stratification of asymptomatic patients with severe AS and preserved LV ejection fraction. Its prognostic value was demonstrated in these patients, but further work is required to define the best thresholds to aid the decision-making process. The assessment of myocardial fibrosis is the most studied application of cardiac magnetic resonance in AS. The detection of replacement fibrosis by late gadolinium enhancement offers incremental prognostic information in these patients. Clinical implementation of this technique to optimise the timing of aortic valve intervention in asymptomatic patients is currently tested in a randomised trial. The use of T1 mapping techniques can provide an assessment of interstitial myocardial fibrosis and represents an expanding field of interest. However, convincing data in patients with AS is still lacking. All these imaging parameters have substantial potential to influence the management decision in patients with AS in the future, but data from randomised clinical trials are awaited to define their utility in daily practice.

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

Heart: 15 Mar 2020; epub ahead of print
Calin A, Mateescu AD, Popescu AC, Bing R, Dweck MR, Popescu BA
Heart: 15 Mar 2020; epub ahead of print | PMID: 32179586
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Abstract

Antiphospholipid Syndrome and the Relationship between Laboratory Assay Positivity and prevalence of Non-Bacterial Thrombotic Endocarditis: A Retrospective Cohort Study.

Lenz CJ, Mankad R, Klarich K, Kurmann R, McBane RD
Background
Non-bacterial thrombotic endocarditis (NBTE) is a potential complication of antiphospholipid syndrome (APS) manifesting as non-infectious lesions on one or more cardiac valves. There are limited tools to inform clinicians regarding which APS patients would benefit most from echocardiographic screening for this complication.
Objectives
We tested the hypothesis that the risk of both prevalent and incident NBTE is directly related to the number of positive laboratory assays for APS.
Patients/methods
In this single-center retrospective cohort study design, consecutive patients with confirmed APS seen at Mayo Clinic Rochester, MN (1/1/1993 - 6/26/2016) were identified by searching a centralized electronic database. Demographic data, clinical presentation, echocardiographic features, laboratory findings and survival data were scrutinized.
Results
During the study period, 611 patients met the diagnostic criteria for APS and 386 (63%) underwent echocardiography. Of these, 58 (15%) were found to have NBTE. NBTE was more common in those with double (19.4%) and triple positive laboratory criteria (27.0%) compared to single positive disease (5.7%, p < 0.001). Survival free of NBTE diagnosis was significantly shorter in those patients with > 1 positive laboratory assay (p < 0.01). Cox-proportional hazard analysis suggests that patients with APS are more likely to be diagnosed with NBTE if they have >1 positive laboratory assay (RR 20.1; 95% CI 1.3-316.6; p <0.03).
Conclusion
APS carries a high prevalence of NBTE (15%). This prevalence is particularly high for patients with either double or triple positive laboratory criteria.

This article is protected by copyright. All rights reserved.

J Thromb Haemost: 16 Mar 2020; epub ahead of print
Lenz CJ, Mankad R, Klarich K, Kurmann R, McBane RD
J Thromb Haemost: 16 Mar 2020; epub ahead of print | PMID: 32180317
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Abstract

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

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



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

Cold-Inducible RNA-Binding Protein Prevents an Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase.

Xie D, Geng L, Xiong K, Zhao T, ... Liang D, Chen YH

The stress response of heart rate (HR), which is determined by the plasticity of the sinus node (SAN), is essential for cardiac function and survival in mammals. As an RNA binding protein, cold-inducible RNA-binding protein (CIRP) can act as a stress regulator. Previously, we\'ve documented that CIRP regulates cardiac electrophysiology at post-transcriptional level, suggesting its role in SAN plasticity, especially upon stress conditions.Our aim was to clarify the role of CIRP in SAN plasticity and HR regulation under stress conditions.Telemetric ECG monitoring demonstrated an excessive acceleration of HR under isoprenaline (ISO) stimulation in conscious CIRP knockout (CIRP-KO) rats. Patch clamp analysis and confocal microscopic Ca2+ imaging of isolated SAN cells (SANCs) demonstrated that ISO stimulation induced a faster spontaneous firing rate in CIRP-KO SANCs than that in wild type (WT) SANCs. A higher concentration of cyclic adenosine monophosphate (cAMP), the key mediator of pacemaker activity, was detected in CIRP-KO SAN tissues than in WT SAN tissues. RNA-sequencing and quantitative real-time polymerase chain reaction (qPCR) analyses of single cells revealed that the 4B and 4D subtypes of phosphodiesterase (PDE), which controls cAMP degradation, were significantly decreased in CIRP-KO SANCs. A PDE4 inhibitor (Rolipram) abolished the difference in beating rate resulting from CIRP deficiency. The mechanistic study showed that CIRP stabilized the mRNA of PDE4B and PDE4D by direct mRNA binding, thereby regulating the protein expression of PDE4B and PDE4D at post-transcriptional level.CIRP acts as an mRNA stabilizer of specific PDEs to control the cAMP concentration in SAN, maintaining the appropriate HR stress response.



Circ Res: 25 Mar 2020; epub ahead of print
Xie D, Geng L, Xiong K, Zhao T, ... Liang D, Chen YH
Circ Res: 25 Mar 2020; epub ahead of print | PMID: 32212953
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Abstract

Epigenetic Metabolic Reprogramming of Right Ventricular Fibroblasts in Pulmonary Arterial Hypertension: A Pyruvate Dehydrogenase Kinase-Dependent Shift in Mitochondrial Metabolism Promotes Right Ventricular Fibrosis.

Tian L, Wu D, Dasgupta A, Chen KH, ... Sutendra G, Archer SL

Right ventricular (RV) fibrosis in pulmonary arterial hypertension (PAH) contributes to RV failure (RVF). While RV fibrosis reflects changes in the function of resident RV fibroblasts (RVfib), these cells are understudied.Examine the role of mitochondrial metabolism of RVfib in RV fibrosis in human and experimental PAH.Male Sprague-Dawley rats received monocrotaline (MCT; 60 mg/kg) or saline. Drinking water containing no supplement or the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate was started 7-days post MCT. At week-4, treadmill testing, echocardiography and right heart catheterization were performed. The effects of PDK activation on mitochondrial dynamics and metabolism, RVfib proliferation, and collagen production were studied in RVfib in cell culture. Epigenetic mechanisms for persistence of the profibrotic RVfib phenotype in culture were evaluated. PDK expression was also studied in the RVfib of patients with decompensated RVF (n=11) versus control (n=7). MCT rats developed PAH, RV fibrosis and RVF. MCT-RVfib (but not left ventricular fibroblasts) displayed excess mitochondrial fission and had increased expression of PDK isoforms 1&3 that persisted for >5 passages in culture. PDK-mediated decreases in pyruvate dehydrogenase (PDH) activity and oxygen-consumption rate were reversed by dichloroacetate (in RVfib and in vivo) or siRNA targeting PDK 1&3 (in RVfib). These interventions restored mitochondrial superoxide and H2O2 production and inactivated hypoxia-inducible factor 1-alpha (HIF-1α), which was pathologically activated in normoxic MCT-RVfib. Redox-mediated HIF-1α inactivation also decreased expression of transforming growth factor beta-1 and connective tissue growth factor, reduced fibroblast proliferation, and decreased collagen production. HIF-1α activation in MCT-RVfib reflected increased DNA methyltransferase 1 (DNMT1) expression, which was associated with a decrease in its regulatory microRNA, miR-148b-3p. In MCT rats, dichloroacetate, at therapeutic levels in the RV, reduced phospho-PDH expression, RV fibrosis and hypertrophy, and improved RV function. In patients with PAH and RVF, RVfib had increased PDK1 expression.MCT-RVfib manifest a DNMT1-HIF-1α-PDK-mediated, chamber-specific, metabolic memory that promotes collagen production and RV fibrosis. This epigenetic mitochondrial-metabolic pathway is a potential antifibrotic therapeutic target.



Circ Res: 26 Mar 2020; epub ahead of print
Tian L, Wu D, Dasgupta A, Chen KH, ... Sutendra G, Archer SL
Circ Res: 26 Mar 2020; epub ahead of print | PMID: 32216531
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Abstract

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

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

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

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

NON-INVASIVE PULMONARY HEMODYNAMIC EVALUATION IN ATHLETES WITH EXERCISE-INDUCED HYPOXEMIA.

Durand F, Gaston AF, Vicenzi M, Deboeck G, Subirats E, Faoro V
Background
Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia i.e., a significant fall in hemoglobin O saturation (SpO) during sea level exercise in endurance-trained athletes. Whether there may be specific properties of the pulmonary vascular function in athletes exhibiting O desaturation is unknown.
Methods
10 endurance trained athletes with exercise induced O desaturation (EIH), 9 endurance trained athletes without (NEIH) and 10 untrained controls underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for CO (DLCO) and NO (DLNO). Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure (Pcap), pulmonary vascular resistance (PVR), cardiac output (Qc) and pulmonary vascular distensibility (α) mathematically determined from the curvilinearity of the multipoint mPAP-Qc relationship.
Results
EIH exhibited lower exercise induced PVR decrease compared to untrained and NEIH groups (p<0.001). EIH athletes showed higher maximal mPAP as compared to NEIH (45.4±0.9 mmHg vs 41.6±0.9 mmHg, p=0.003, respectively) while no difference appeared between NEIH and untrained. Alpha was lower in EIH compared to NEIH (p<0.05). Maximal mPAP, Pcap and alpha were correlated with the fall of SpO during exercise (p<0.01, p<0.01 and p<0.05 respectively). DLNO and DLCO increased with exercise in all groups without difference between groups while DLNO/Qc was correlated to the exercise induced SpO changes (p<0.05).
Conclusions
EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility or exercise induced changes in PVR compared to NEIH subjects, in keeping with pulmonary capillary stress failure or intra-pulmonary shunting hypotheses.

Copyright © 2020. Published by Elsevier Inc.

Chest: 16 Feb 2020; epub ahead of print
Durand F, Gaston AF, Vicenzi M, Deboeck G, Subirats E, Faoro V
Chest: 16 Feb 2020; epub ahead of print | PMID: 32081649
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Abstract

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

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

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

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

Echocardiographic evaluation of left ventricular filling pressure in patients with heart failure with preserved ejection fraction: usefulness of inferior vena cava measurements and 2016 EACVI/ASE recommendations.

Berthelot E, Jourdain P, Bailly MT, Bouchachi A, ... Chemla D, Assayag P

Context;: The left ventricular filling pressure (LVFP) is correlated to right atrial pressure (RAP) in heart failure.  We compared diagnostic value of the inferior vena cava (IVC) measurements to the one of the 2016 echocardiographic recommendations to estimate LVFP in patients with suspected heart failure with preserved ejection fraction (HFpEF). METHODS;: Invasive hemodynamics and echocardiography were obtained within 48h in 132 consecutive patients with left ventricular ejection fraction (LVEF)≥50%, and suspected pulmonary hypertension. Increased LVFP was defined by a pulmonary artery wedge pressure (PAWP)>15mmHg. RESULTS;: In 83 sinus rhythm patients, a score of the 2016 recommendations ≥ 2 (E/e\' ratio >14 and/or tricuspid regurgitation velocity>2.8m/s and/or indexed left atrial volume>34ml/m²) had a PPV of 63% for PAWP>15mmHg, whereas a dilated IVC (>2.1 cm) and/or non-collapsible (≤50%) had a PPV of 83%. The net reclassification improvement was 0.44 (p<0.05). In atrial fibrillation (AF), a dilated and/or non-collapsible IVC had an 86% PPV for PAWP>15mmHg. The correlation between RAP and PAWP was 0.60, with 75.7% concordance (100/132) between dichotomized pressures (both RAP>8 mmHg and PAWP>15mmHg and vice-versa). CONCLUSION;: The IVC size and collapsibility is valuable to identify HFpEF patients with high LVFP in both sinus rhythm and AF.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 29 Jan 2020; epub ahead of print
Berthelot E, Jourdain P, Bailly MT, Bouchachi A, ... Chemla D, Assayag P
J Card Fail: 29 Jan 2020; epub ahead of print | PMID: 32007555
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Abstract

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

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

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

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

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

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

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

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

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

A 78-Year-Old Man With Recurrent Hemoptysis and Persistent Pulmonary Nodule.

Chew SY, Tan CS, Puan Y, Koh JMK
Case presentation
A 78-year-old Chinese man presented in March 2019 with a 2-day history of small-volume hemoptysis. He did not report any associated chronic cough, sputum production, epistaxis, night sweats, unintentional weight loss, or fever. He was an ex-smoker of 10 pack years. His medical history was significant for ischemic heart disease on aspirin, as well as hospitalizations in 2016 and 2017 for hemoptysis. The patient\'s evaluation for hemoptysis was only notable for a right middle lobe nodule on chest CT imaging and Klebsiella pneumoniae on sputum cultures, for which he was treated with antibiotics.

Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Chest: 28 Feb 2020; 157:e79-e84
Chew SY, Tan CS, Puan Y, Koh JMK
Chest: 28 Feb 2020; 157:e79-e84 | PMID: 32145821
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Abstract

Accurate Conduction Velocity Maps and their Association with Scar Distribution on Magnetic Resonance Imaging in Patients with Post-Infarction Ventricular Tachycardias.

Aronis KN, Ali RL, Prakosa A, Ashikaga H, ... Chrispin J, Trayanova NA

- Characterizing myocardial conduction velocity (CV) in patients with ischemic cardiomyopathy (ICM) and ventricular tachycardia (VT) is important for understanding the patient-specific pro-arrhythmic substrate of VTs and therapeutic planning. The objective of this study is to accurately assess the relation between CV and myocardial fibrosis density on late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging in patients with ICM.- We enrolled 6 patients with ICM undergoing VT ablation and 5 with structurally normal left ventricles (controls) undergoing PVC or VT ablation. All patients underwent LGE-CMR and electro-anatomical mapping (EAM) in sinus rhythm (2,960 EAM points analyzed). We estimated CV from EAM local activation time using the triangulation method, that provides an accurate estimate of CV as it accounts for the direction of wavefront propagation. We evaluated for the association between LGE-CMR intensity and CV with multi-level linear mixed models.- Median CV in ICM patients and controls was 0.41 m/s and 0.65 m/s respectively. In ICM patients, CV in areas with no visible fibrosis was 0.81 m/s (95%CI: 0.59-1.12 m/s). For each 25% increase in normalized LGE intensity CV decreased by 1.34-fold (95%CI: 1.25-1.43). Dense scar areas have on average 1.97-2.66-fold slower CV compared to areas without dense scar. Ablation lesions that terminated VTs were localized in areas of slow conduction on CV maps.- CV is inversely associated with LGE-CMR fibrosis density in patients with ICM. Non-invasive derivation of CV maps from LGE-CMR is feasible. Integration of non-invasive CV maps with EAM during substrate mapping has the potential to improve procedural planning and outcomes.



Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print
Aronis KN, Ali RL, Prakosa A, Ashikaga H, ... Chrispin J, Trayanova NA
Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print | PMID: 32191131
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Abstract

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

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

Copyright © 2019. Published by Elsevier B.V.

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

Impact of Cardiac Resynchronization Therapy on Heart Transplant-Free Survival in Pediatric and Congenital Heart Disease Patients.

Chubb H, Rosenthal DN, Almond CS, Ceresnak SR, ... McElhinney DB, Dubin AM

- Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis.- This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years or had CHD; had systemic ventricular ejection fraction <;45%; symptomatic heart failure; and had significant electrical dyssynchrony, all prior to CRT implant. Controls were screened from non-selective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period.- Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p<0.001). There was no CRT procedural mortality and one system infection at 54 months post-implant.- In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.



Circ Arrhythm Electrophysiol: 21 Mar 2020; epub ahead of print
Chubb H, Rosenthal DN, Almond CS, Ceresnak SR, ... McElhinney DB, Dubin AM
Circ Arrhythm Electrophysiol: 21 Mar 2020; epub ahead of print | PMID: 32202126
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Abstract

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

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

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

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

Dynamic changes in cardiac function before and early postdelivery in women with severe preeclampsia.

Ambrožič J, Lučovnik M, Prokšelj K, Toplišek J, Cvijić M
Objectives
In women with severe preeclampsia the period immediately before and early postdelivery carries the greatest risk for cardiac decompensation due to acute changes in loading conditions. The authors aimed to evaluate dynamic changes in hemodynamic and echocardiographic-derived systolic and diastolic function parameters in preeclamptic women compared with healthy controls.
Methods
Thirty women with severe preeclampsia and 30 healthy controls underwent transthoracic echocardiography 1 day before, 1 and 4 days postdelivery. Fluid responsiveness was assessed by passive leg raising.
Results
Peak systolic myocardial velocities (s\') and global longitudinal strain (GLS) were significantly lower in preeclamptic group compared with controls only postdelivery (s\': 7.3 ± 0.8 vs. 8.3 ± 0.9 cm/s, P < 0.001; GLS: -21.4 ± 2.0 vs. -23.0 ± 1.4%, P = 0.027). In addition, significant decrease in s\' after delivery was observed only in preeclamptic group (P = 0.004). For diastolic parameters there were differences both before and postdelivery in E/e\' ratio (before: 8.4 ± 2.16 vs. 6.7 ± 1.89, P = 0.002; postdelivery: 8.3 ± 1.64 vs. 6.8 ± 1.27, P = 0.003) and mitral e\' velocity (before: 11.0 ± 2.39 vs. 12.6 ± 1.86, P = 0.004; postdelivery: 11.1 ± 2.28 vs. 14.0 ± 2.40 cm/s, P < 0.001). Significant increase in left ventricular stroke volume (P = 0.005) and transmitral E velocity (P = 0.003) was observed only in control group, reflecting response to volume load after delivery. Accordingly, only the minority of preeclamptic women were fluid responsive (11 vs. 43%, P = 0.014 between groups).
Conclusion
Variations in cardiac parameters in healthy women seem to follow changes in loading conditions before and early after delivery. Different pattern in preeclamptic women, however, may be related to subtle myocardial dysfunction, that becomes uncovered with augmented volume load in early postpartum period.



J Hypertens: 12 Mar 2020; epub ahead of print
Ambrožič J, Lučovnik M, Prokšelj K, Toplišek J, Cvijić M
J Hypertens: 12 Mar 2020; epub ahead of print | PMID: 32195819
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Abstract

Differences in hypertension phenotypes between Africans and Europeans: role of environment.

Faconti L, Mcnally RJ, Farukh B, Adeyemi O, ... Chowienczyk PJ, Ojji D
Objectives
Hypertension phenotypes differ between Africans and Europeans, with a greater prevalence of low renin salt-sensitive hypertension and greater predisposition to adverse cardiac remodelling in Africans. To elucidate the roles of inheritance and environment in determining hypertension phenotypes in sub-Saharan Africans and white Europeans, we compared phenotypes in white individuals in the UK (n = 132) and in African individuals in the UK (n = 158) and Nigeria (n = 179).
Methods
Biochemistry, blood pressure, left ventricular structure (echocardiography) and 24-h urinary collections of sodium and potassium were measured.
Results
Twenty-four-hour urinary sodium/potassium ratio was lower in individuals living in Europe (both African and white: 2.32 ± 0.15 and 2.28 ± 0.17) than in individuals in Nigeria (4.09 ± 0.26, both P < 0.001) reflecting proportionately higher potassium intake in Europeans (African or white) than African residents. Plasma renin was lower in Africans irrespective of residency than white Europeans, but aldosterone was higher in Africans in Europe than those in Africa (466.15 ± 32.95 vs. 258.60 ± 17.42 pmol/l, P < 0.001). Left ventricular mass index adjusted for blood pressure and other confounders was greatest in Africans in Europe (103.27 ± 2.32 g/m) compared with those in Africa (89.28 ± 1.98 g/m) or white Europeans (86.77 ± 2.63 g/m, both P < 0.001).
Conclusion
Despite a similar low renin state in African origin individuals living in Europe and Africa, a higher aldosterone level, possibly related to higher potassium intake or other environmental factors, may contribute to greater cardiac remodelling in Africans in Europe.



J Hypertens: 18 Mar 2020; epub ahead of print
Faconti L, Mcnally RJ, Farukh B, Adeyemi O, ... Chowienczyk PJ, Ojji D
J Hypertens: 18 Mar 2020; epub ahead of print | PMID: 32205559
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Abstract

Echocardiography-derived stroke volume index is associated with adverse in-hospital outcomes in intermediate-risk acute pulmonary embolism: a retrospective cohort study.

Prosperi-Porta G, Solverson K, Fine N, Humphreys CJ, Ferland A, Weatherald J
Background
There remains uncertainty in the optimal prognostication and management of patients with intermediate-risk PE. Transthoracic echocardiography can identify right ventricular (RV) dysfunction to recognise intermediate-high risk patients.
Research question
The aim of this study was to test whether echocardiography-derived stroke volume index (SVI) is associated with death or cardiopulmonary decompensation in intermediate-risk patients with pulmonary embolism (PE).
Study design and methods
We retrospectively evaluated echocardiographic-derived variables including SVI in normotensive patients with acute pulmonary embolism admitted between January 2012 and March 2017. SVI was determined using the Doppler velocity-time integral in the left or right ventricular outflow tract. The primary outcome was in-hospital PE-related death or cardiopulmonary decompensation. We used logistic regression to determine the association between SVI and outcomes, and receiver operating characteristic analysis to compare the performance of SVI and other echocardiographic measures.
Results
The primary outcome occurred in 26 (3.9%) of the 665 intermediate-risk PE patients. Univariate logistic regression showed an odds ratio of 1.37 (95% CI, 1.23-1.52, p<0.001) per 1 mL/m decrease in SVI for the primary outcome. Bivariate logistic regression showed that SVI was independent of age, sex, heart rate, VTI and Bova score. SVI had the highest C-statistic of 0.88 (95% CI, 0.81-0.96) of all echocardiographic variables with a Youden\'s J-statistic identifying an optimal cut-point of 20.0 mL/m, which corresponds to positive and negative likelihood ratios of 6.5 (95% CI, 5.0-8.6) and 0.2 (95% CI, 0.1-0.5) for the primary outcomes, respectively.
Interpretation
Low SVI was associated with in-hospital death or cardiopulmonary decompensation in acute PE. SVI had excellent performance compared to other clinical and echocardiographic variables.

Copyright © 2020. Published by Elsevier Inc.

Chest: 30 Mar 2020; epub ahead of print
Prosperi-Porta G, Solverson K, Fine N, Humphreys CJ, Ferland A, Weatherald J
Chest: 30 Mar 2020; epub ahead of print | PMID: 32243942
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Abstract

Sex Differences in Exercise Capacity and Quality of Life in Heart Failure with Preserved Ejection Fraction: A Secondary Analysis of the RELAX and NEAT-HFpEF Trials.

Honigberg MC, Lau ES, Jones AD, Coles A, ... Lewis GD, Givertz MM
Background
Few studies have compared clinical characteristics, echocardiographic parameters, exercise capacity, and quality of life between women and men with heart failure with preserved ejection fraction (HFpEF).
Methods and results
Subjects in the NIH-sponsored RELAX (N = 216) and NEAT (N = 107) trials completed baseline echocardiography, the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-minute walk test (6MWT). In exploratory analysis, multivariable linear regression models were used to associate clinical and imaging characteristics with baseline 6MWT distance and MLHFQ score in women and men. Our cohort included 158 (49%) men and 165 (51%) women. Men had higher prevalence of atrial arrhythmias, ischemic heart disease, diabetes, anemia, and left ventricular (LV) hypertrophy. 6MWT and MLHFQ score did not differ between sexes. In multivariable analysis, ischemic heart disease, diastolic dysfunction, and exercise capacity predicted MLHFQ score for men, while only age and BMI predicted MLHFQ score for women.
Conclusions
Men with HFpEF had more co-morbidities and LV hypertrophy than women with HFpEF. In men, quality of life was associated with diastolic dysfunction, ischemic heart disease, and exercise capacity. Further research is needed to identify determinants of quality of life in women with HFpEF.

Copyright © 2020. Published by Elsevier Inc.

J Card Fail: 12 Jan 2020; epub ahead of print
Honigberg MC, Lau ES, Jones AD, Coles A, ... Lewis GD, Givertz MM
J Card Fail: 12 Jan 2020; epub ahead of print | PMID: 31945458
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Abstract

Predictors of Adverse Outcome in Patients with Frequent Premature Ventricular Complexes: the ABC-VT Risk Score.

Voskoboinik A, Hadjis A, Alhede C, Im SI, ... Park KM, Gerstenfeld EP
Background
No independently-validated score currently exists for risk stratification of patients with frequent premature ventricular contractions (PVCs).
Objectives
To develop a risk score to predict adverse events in patients with frequent PVCs.
Methods
We analyzed consecutive patients between 2012-2017 undergoing 14-day continuous monitoring with frequent PVCs (>5%) and concurrent echocardiography. We performed binary logistic regression to determine multivariate predictors of adverse LV remodeling (LVEF<45% or LVEDVI>75 mL/m). A risk score was created using the log-OR of these predictors and validated prospectively to determine the risk of future adverse events in those with baseline LVEF > 45%. An adverse event was defined as LVEF decline by 10%, heart failure hospitalization or cardiovascular mortality. Two validation cohorts were used: follow-up from the original derivation cohort (cohort 1) and an independent Korean PVC registry (cohort 2).
Results
The derivation cohort comprised 206 patients with mean PVC burden 11.6±6.2% and considerable daily fluctuation (minimum burden 7.3±6.2% versus maximum 17.9±8.0%). Independent predictors of adverse remodeling were: superiorly-directed PVC Axis (OR 2.7, 1 point), PVC Burden 10-20% (OR 3.5, 2 points) & > 20% (OR 4.4, 3 points), PVC Coupling Interval>500ms (OR 4.7, 4 points), Non-sustained VT (OR 5.3, 4 points), forming the ABC-VT risk score. This score predicted future adverse events in both validation cohorts: Cohort 1 HR 1.43; 95%CI 1.19-1.73;p<0.001, Cohort 2 HR 1.22; 95%CI 1.05-1.42;p=0.01.
Conclusion
The ABC-VT score is a simple tool that predicts adverse LV remodeling and future clinical deterioration in patients with frequent PVCs.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 24 Feb 2020; epub ahead of print
Voskoboinik A, Hadjis A, Alhede C, Im SI, ... Park KM, Gerstenfeld EP
Heart Rhythm: 24 Feb 2020; epub ahead of print | PMID: 32109563
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Abstract

Stereotactic arrhythmia radioablation for refractory scar-related ventricular tachycardia.

Gianni C, Rivera D, Burkhardt JD, Pollard B, ... Natale A, Al-Ahmad A
Background
Recently, stereotactic radiosurgery has been applied to arrhythmias (stereotactic arrhythmia radioablation - STAR), with promising results reported in patients with refractory, scar-related VT, a cohort with known high morbidity and mortality.
Objective
Herein, we describe our experience with STAR, detailing its early and mid- to long-term results.
Methods
This is a pilot, prospective study of patients undergoing STAR for refractory, scar-related VT. The anatomical target for radioablation was defined based on the clinical VT morphology, electroanatomical mapping, and study-specific pre-procedural imaging with cardiac CT. The target volume was treated with a prescription radiation dose of 25 Gy delivered in a single fraction by CyberKnife in an outpatient setting. Ventricular arrhythmias and radiation-related adverse events were monitored at follow-up to determine STAR efficacy and safety.
Results
Five patients (100% male, 63±12 years old, 80% ischemic cardiomyopathy, LVEF 34±15%) underwent STAR. Radioablation was delivered in 82±11 minutes without acute complications. During a mean follow-up of 12±2 months, all patients experienced clinically significant mid- to late-term ventricular arrhythmia recurrence; two patients died of complications associated with their advanced heart failure. There were no clinical or imaging evidence of radiation-induced complications in the organs at risk surrounding the scar targeted by radioablation.
Conclusion
Despite good initial results, STAR did not result in effective arrhythmia control in the long term in a selected, high-risk population of patients with scar-related VT. The safety profile was confirmed to be favorable, with no radiation-related complications observed during follow-up. Further studies are needed to explain these disappointing results.

Copyright © 2020. Published by Elsevier Inc.

Heart Rhythm: 05 Mar 2020; epub ahead of print
Gianni C, Rivera D, Burkhardt JD, Pollard B, ... Natale A, Al-Ahmad A
Heart Rhythm: 05 Mar 2020; epub ahead of print | PMID: 32151737
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Abstract

Primacy of coronary CT angiography as the gatekeeper for the cardiac catheterization laboratory.

Meah MN, Bing R, Newby DE

Determining the underlying etiology of chest pain remains a mainstay of modern cardiological practice and is focused on identifying coronary artery disease to improve both symptoms and prognosis. In the current age of multi-modality imaging, the expanding repertoire of tests has subjected clinicians to a tyranny of choices. In whom should we perform further investigations? What non-invasive modality should be used? Which test is the best gatekeeper for invasive coronary angiography? In this week\'s American Heart Journal, Houssany-Pissot and colleagues present real-world data from a large French cohort of patients who present with suspected stable coronary artery disease undergoing invasive coronary angiography. Their findings demonstrate that compared to functional testing, coronary computed tomography angiography is associated with fewer normal invasive coronary angiograms and more patients with actionable disease. Moreover, this was apparent irrespective of the pre-test probability of obstructive coronary artery disease. The consistency of this study with data from randomised trials and observational registries leads us to agree that computed tomography has primacy as gatekeeper for the cardiac catheter laboratory irrespective of the level of pre-test probability. This latest addition to the growing and large body of evidence does beg the question of why guidelines do not now recommend CCTA as the first line test of choice for the non-invasive investigation of all patients with stable coronary artery disease?

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

Am Heart J: 29 Jan 2020; epub ahead of print
Meah MN, Bing R, Newby DE
Am Heart J: 29 Jan 2020; epub ahead of print | PMID: 32081302
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Abstract

Coronary Artery Disease Assessed by Computed Tomography-Based Leaman Score in Patients With Low-Risk Transcatheter Aortic Valve Implantation.

Ozaki Y, Garcia-Garcia HM, Rogers T, Torguson R, ... Satler LF, Waksman R

We aimed to evaluate the burden of coronary artery disease (CAD) using the computed tomography (CT) Leaman score in low-risk transcatheter aortic valve implantation (TAVI) patients. The extent of CAD in low-risk patients with aortic stenosis who are candidates for TAVI has not been accurately quantified. The CT Leaman score was developed to quantify coronary CT angiography (CCTA) atherosclerotic burden and has been validated to evaluate the extent of CAD. CT Leaman score >5 has been associated with an increase in major adverse cardiac events over long-term follow-up. The study population included patients enrolled in the Low Risk TAVI trial who underwent CCTA before the procedure. For the CT Leaman score, we used 3 sets of weighting factors: (1) location of coronary plaques, (2) type of plaque, and (3) degree of stenosis. A total of 200 patients were enrolled in the Low Risk TAVI trial. Excluded were 31 patients who had no analyzable CCTA imaging. For the remaining 169 patients, the mean CT Leaman score was 6.27 ± 0.27, of whom 102 (60.4%) had CT Leaman score >5. Nearly all analyzed patients (97%) had coronary plaques. Furthermore, 33 patients (19.5%) had potentially obstructive coronary plaques (>50% stenosis by CCTA) in proximal segments. Most low-risk TAVI patients have significant CAD burden by CCTA. It should be a priority for future TAVI devices to guarantee unimpeded access to the coronary arteries for selective angiography and interventions.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 27 Jan 2020; epub ahead of print
Ozaki Y, Garcia-Garcia HM, Rogers T, Torguson R, ... Satler LF, Waksman R
Am J Cardiol: 27 Jan 2020; epub ahead of print | PMID: 32087995
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Abstract

Cardiac Magnetic Resonance Imaging Features in Hypertrophic Cardiomyopathy Diagnosed at <21 Years of Age.

Bonura ED, Bos JM, Abdelsalam MA, Araoz PA, ... Ackerman MJ, Geske JB

Hypertrophic cardiomyopathy (HC) is the most common inherited cardiomyopathy, with varied timing of phenotypic and clinical presentation. Literature describing cardiac magnetic resonance (CMR) imaging and late gadolinium enhancement (LGE) in young patients with HC is limited. This study included patients diagnosed with HC at young age (<21 years) between January 1990 and January 2015 who underwent transthoracic echocardiography and CMR with assessment of LGE at a single tertiary referral center. LGE was quantified via a method of 6 standard deviations and patients were grouped based upon presence or absence of LGE (≤1% and >1% LGE, respectively). Sudden cardiac death (SCD) risk was assessed in patients >16 years of age using the European SCD risk score. A composite outcome of New York Heart Association class III-IV symptoms, aborted SCD, heart transplantation, and all-cause mortality was assessed via Kaplan-Meier curves with log-rank analysis. Overall, 126 patients were included (78 male; 62%). Median age of diagnosis was 15 (12 to 18) years. LGE was present in 81 (64%) patients, although only 4 (3%) patients had LGE >15%. Median age at CMR imaging was 19 (15 to 23) years. Patients with LGE had greater wall thickness (25 ± 8 mm vs 22 ± 7 mm, p = 0.01). Median European SCD risk score was 4.7 (2.9 to 6.5). Median follow-up was 6.5 (2.5 to 13) years with 26 patients (21%) meeting the composite outcome. There were no significant differences in composite outcome since age of diagnosis when stratified by presence/absence of LGE (p = 1.0). The presence of LGE in young HC patients was not an independent risk factor for cardiovascular morbidity and mortality. Wall thickness was greater in patients with LGE. There remains a need for further evaluation of this unique HC cohort.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 27 Jan 2020; epub ahead of print
Bonura ED, Bos JM, Abdelsalam MA, Araoz PA, ... Ackerman MJ, Geske JB
Am J Cardiol: 27 Jan 2020; epub ahead of print | PMID: 32088002
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Abstract

Basal Ventricular Septal Hypertrophy in Systemic Hypertension.

Loncaric F, Nunno L, Mimbrero M, Marciniak M, ... Bijnens B, Sitges M

Basal septal hypertrophy (BSH) is commonly seen in patients with systemic hypertension and has been associated with increased afterload. The impact of localized hypertrophy on left ventricular (LV) and left atrial (LA) function is still unclear. Our aim is to investigate if BSH is a marker of a more pronounced impact of hypertension on cardiac function in the early stages of hypertensive heart disease. An echocardiogram was performed in 163 well-controlled hypertensive patients and 22 healthy individuals. BSH was defined by a basal-to-mid septal thickness ratio ≥1.4. LV dimensions and mass were evaluated. LV global and regional deformation was assessed by 2-dimensional (2D) speckle tracking echocardiography, and LV diastolic function by 2D and Doppler imaging. LA function was evaluated with phasic volume indices calculated from 2D and 3-dimensional volumes, as well as speckle tracking echocardiography. The population was 54% men, mean age 57 (53 to 60) years. BSH was seen in 20% (n = 32) of the hypertensive cohort. Patients with BSH showed decreased regional LV systolic deformation, impaired LV relaxation with a higher proportion of indeterminate LV diastolic function, and LA functional impairment defined by a reduction of reservoir strain and a change in LA functional dynamics. In conclusion, in well-controlled hypertension impairment of LV and LA function is present in patients with early LV remodeling and localized hypertrophy. BSH might be useful as an early marker of the burden of hypertensive heart disease.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Am J Cardiol: 07 Feb 2020; epub ahead of print
Loncaric F, Nunno L, Mimbrero M, Marciniak M, ... Bijnens B, Sitges M
Am J Cardiol: 07 Feb 2020; epub ahead of print | PMID: 32164912
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Abstract

Effect of Physical Exercise Training in Patients With Chagas Heart Disease (from the PEACH STUDY).

de Souza Nogueira Sardinha Mendes F, Felippe Felix Mediano M, de Castro E Souza FC, da Silva PS, ... Americano do Brasil PEA, de Sousa AS

Chagas heart disease (HD) is a chronic fibrosing myocarditis with high mortality. The PEACH study aimed to evaluate if exercise training can improve the functional capacity of Chagas HD patients with left ventricular dysfunction and/or heart failure. The PEACH study was a single center, parallel-group, clinical trial that randomized 30 clinical stable Chagas HD patients with left ventricular ejection fraction <45% or heart failure symptoms to either supervised exercise training 3 times/week for 6 months or a control group. Both groups had the same monthly pharmaceutical and nutritional counseling and usual care. Primary end point was functional capacity assessed by peak exercise oxygen consumption (peak VO) obtained by cardiopulmonary exercise test. Secondary end points included other cardiopulmonary exercise test variables, cardiac function by echocardiography, body composition, muscle respiratory strength, and metabolic biomarkers. Peak VO increased among patients in exercise group from 17.60 ± 4.65 mlO kg min to 19.40 ± 5.51 mlO kg min while decreased in controls from 15.40 ± 6.30 mlO kg min to 12.96 ± 4.50 mlO kg min, resulting in significant difference in change in peak VO between groups after 6 months (β = +4.6, p = 0.004). There were significant differences between groups in changes in anaerobic threshold (β = 3.7, p = 0.05), peak oxygen pulse (β = +2.7, p = 0.032) and maximum minute ventilation (β = +13.9, p < 0.0001) after 6 months of intervention. In conclusion, exercise training improved functional capacity of chronic Chagas HD patients with left ventricular dysfunction and/or heart failure.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am J Cardiol: 09 Feb 2020; epub ahead of print
de Souza Nogueira Sardinha Mendes F, Felippe Felix Mediano M, de Castro E Souza FC, da Silva PS, ... Americano do Brasil PEA, de Sousa AS
Am J Cardiol: 09 Feb 2020; epub ahead of print | PMID: 32171439
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Abstract

Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy.

Finocchiaro G, Dhutia H, Gray B, Ensam B, ... Papadakis M, Sharma S
Aims
Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM.
Methods and results 
Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff-Parkinson-White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family.
Conclusion 
Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

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

Europace: 02 Feb 2020; epub ahead of print
Finocchiaro G, Dhutia H, Gray B, Ensam B, ... Papadakis M, Sharma S
Europace: 02 Feb 2020; epub ahead of print | PMID: 32011662
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Abstract

Impact of the Inflammation on the outcomes of catheter ablation of drug refractory ventricular tachycardia in Cardiac Sarcoidosis.

Kaur D, Roukoz H, Shah M, Yalagudri S, ... Chennapragada S, Narasimhan C
Introduction
Catheter ablation (CA) of ventricular tachycardia (VT) in cardiac sarcoidosis (CS) has been reported with varying success. However, there is a scarcity of data on the outcomes of CA based on ongoing inflammation.
Objective
We hypothesized that the response to VT ablation depends upon the stage of disease.
Methods
Between July 2004 and December 2018, 24 patients of CS presented with drug refractory VT at CARE Hospital(Hyderabad) and the University of Minnesota (Minneapolis, MN). Patients were classified into two groups based on cardiac magnetic resonance imaging and Positron emission tomography: A. Inflammatory phase, B. scar phase. All patients underwent 3D electro-anatomic mapping guided CA.
Results
The clinical VT was ablated in all but one patient. In 16 patients (66.6%), both the clinical and non-clinical VTs were ablated (complete success), while in 7 patients (29.1%) non-clinical VTs were still inducible. In patients with inflammation (group A), complete success for VT ablation was achieved in 10/17 (58.8%). In patients without inflammation (group B), complete success was achieved in 6/7 patients (85.7%). Eleven patients (45.8%) had recurrence of VT. Among patients in the inflammatory phase (group A): 10/17 patients had recurrence of VT, while only 1/7 patients in the scar phase (group B) had VT recurrence over a mean follow-up of 5.7 ± 3.9 years. Epicardial ablation was performed in 10 (41.6%) patients.
Conclusion
Catheter ablation of drug-refractory VT in CS is effective, often requiring epicardial approach. Incomplete success and recurrence of VT was higher in the inflammatory phase of the disease. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 08 Jan 2020; epub ahead of print
Kaur D, Roukoz H, Shah M, Yalagudri S, ... Chennapragada S, Narasimhan C
J Cardiovasc Electrophysiol: 08 Jan 2020; epub ahead of print | PMID: 31916658
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Abstract

Magnetic resonance imaging in non-conditional pacemakers and implantable cardioverter-defibrillators: a systematic review and meta-analysis.

Munawar DA, Chan JEZ, Emami M, Kadhim K, ... Sanders P, Lau DH
Aims
There is growing evidence that magnetic resonance imaging (MRI) scanning in patients with non-conditional cardiac implantable electronic devices (CIEDs) can be performed safely. Here, we aim to assess the safety of MRI in patients with non-conditional CIEDs.
Methods and results
English scientific literature was searched using PubMed/Embase/CINAHL with keywords of \'magnetic resonance imaging\', \'pacemaker\', \'implantable defibrillator\', and \'cardiac resynchronization therapy\'. Studies assessing outcomes of adverse events or significant changes in CIED parameters after MRI scanning in patients with non-conditional CIEDs were included. References were excluded if the MRI conditionality of the CIEDs was undisclosed; number of patients enrolled was <10; or studies were case reports/series. About 35 cohort studies with a total of 5625 patients and 7196 MRI scans (0.5-3 T) in non-conditional CIEDs were included. The overall incidence of lead failure, electrical reset, arrhythmia, inappropriate pacing and symptoms related to pocket heating, or torque ranged between 0% and 1.43%. Increase in pacing lead threshold >0.5 V and impedance >50Ω was seen in 1.1% [95% confidence interval (CI) 0.7-1.8%] and 4.8% (95% CI 3.3-6.4%) respectively. The incidence of reduction in P- and R-wave sensing by >50% was 1.5% (95% CI 0.6-2.9%) and 0.4% (95% CI 0.06-1.1%), respectively. Battery voltage reduction of >0.04 V was reported in 2.2% (95% CI 0.2-6.1%).
Conclusion
This meta-analysis affirms the safety of MR imaging in non-conditional CIEDs with no death or implantable cardioverter-defibrillator shocks and extremely low incidence of lead or device-related complications.

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

Europace: 28 Jan 2020; epub ahead of print
Munawar DA, Chan JEZ, Emami M, Kadhim K, ... Sanders P, Lau DH
Europace: 28 Jan 2020; epub ahead of print | PMID: 31995177
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Abstract

Clinical Utility of Echocardiography in Former Preterm Infants with Bronchopulmonary Dysplasia.

Nawaytou H, Steurer MA, Zhao Y, Guslits E, ... Fineman JR, Keller RL
Background
The clinical utility of echocardiography for the diagnosis of pulmonary vascular disease (PVD) in former preterm infants with bronchopulmonary dysplasia (BPD) is not established. Elevated pulmonary vascular resistance (PVR) rather than pulmonary artery pressure (PAP) is the hallmark of PVD. We evaluated the utility of echocardiography in infants with BPD in diagnosing pulmonary hypertension and PVD (PVR >3 Wood units × m) assessed by cardiac catheterization.
Methods
A retrospective single center study of 29 infants born ≤29 weeks of gestational age with BPD who underwent cardiac catheterization and echocardiography was performed. PVD was considered present by echocardiography if the tricuspid valve regurgitation jet peak velocity was >2.9 m/sec, post-tricuspid valve shunt systolic flow velocity estimated a right ventricular systolic pressure >35 mm Hg, or systolic septal flattening was present. The utility (accuracy, sensitivity, and positive predictive value [PPV]) of echocardiography in the diagnosis of PVD was tested. Subgroup analysis in patients without post-tricuspid valve shunts was performed. Echocardiographic estimations of right ventricular pressure, dimensions, function, and pulmonary flow measurements were evaluated for correlation with PVR.
Results
The duration between echocardiography and cardiac catheterization was a median of 1 day (interquartile range, 1-4 days). Accuracy, sensitivity, and PPV of echocardiography in diagnosing PVD were 72%, 90.5%, and 76%, respectively. Accuracy, sensitivity, and PPV increased to 93%, 91.7%, and 100%, respectively, when infants with post-tricuspid valve shunts were excluded. Echocardiography had poor accuracy in estimating the degree of PAP elevation by cardiac catheterization. In infants without post-tricuspid valve shunts, there was moderate to good correlation between indexed PVR and right ventricular myocardial performance index (rho = 0.89, P = .005), systolic to diastolic time index (0.84, P < .001), right to left ventricular diameter ratio at end systole (0.66, P = .003), and pulmonary artery acceleration time (0.48, P = .05).
Conclusions
Echocardiography performs well in screening for PVD in infants with BPD and may be diagnostic in the absence of a post-tricuspid valve shunt. However, cardiac catheterization is needed to assess the degree of PAP elevation and PVR. The diagnostic utility of echocardiographic measurements that correlate with PVR should be evaluated prospectively in this patient population.

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

J Am Soc Echocardiogr: 12 Jan 2020; epub ahead of print
Nawaytou H, Steurer MA, Zhao Y, Guslits E, ... Fineman JR, Keller RL
J Am Soc Echocardiogr: 12 Jan 2020; epub ahead of print | PMID: 31948712
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Abstract

Impact of age, sex and heart rate variability on the acute cardiovascular response to isometric handgrip exercise.

Cauwenberghs N, Cornelissen V, Christle JW, Hedman K, ... Haddad F, Kuznetsova T

Isometric handgrip exercise (IHG) triggers acute increases in cardiac output to meet the metabolic demands of the active skeletal muscle. An abnormal cardiovascular response to IHG might reflect early stages of cardiovascular disease. In a large community-based cohort, we comprehensively assessed the clinical correlates of acute cardiovascular changes during IHG. In total, 333 randomly recruited subjects (mean age, 53 ± 13 years, 45% women) underwent simultaneous echocardiography and finger applanation tonometry at rest and during 3 min of IHG at 40% maximal handgrip force. We calculated time-domain measures of short-term heart rate variability (HRV) from finger pulse intervals. We assessed the adjusted associations of changes in blood pressure (BP) and echocardiographic indexes with clinical characteristics and HRV measures. During IHG, men presented a stronger absolute increase in heart rate, diastolic BP, left ventricular (LV) volumes and cardiac output than women, even after adjustment for covariables. In adjusted continuous and categorical analyses, age correlated positively with the increase in systolic BP and pulse pressure, but negatively with the increase in LV stroke volume and cardiac output during exercise. After full adjustment, a greater increase in systolic and diastolic BP during exercise was associated with lower absolute real variability (P ≤ 0.026) and root mean square of successive differences (P ≤ 0.032) in pulse intervals at rest. In a general population sample, women presented a weaker cardiovascular response to IHG than men. Older age was associated with greater rise in BP pulsatility and diminished cardiac reserve. Low HRV at rest predicted a higher BP increase during isometric exercise.



J Hum Hypertens: 09 Feb 2020; epub ahead of print
Cauwenberghs N, Cornelissen V, Christle JW, Hedman K, ... Haddad F, Kuznetsova T
J Hum Hypertens: 09 Feb 2020; epub ahead of print | PMID: 32042073
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Abstract

Dual 1:2 tachycardia: what is the mechanism?

Karimli E, Kara M, Korkmaz A, Cay S, ... Topaloglu S, Aras D

A 40-year-old female with a history of narrow complex tachycardia (NCT) was referred for radiofrequency ablation. Twelve-lead ECG was normal during sinus rhythm. Her physical examination was normal, and echocardiography revealed no evidence of structural heart disease. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 11 Jan 2020; epub ahead of print
Karimli E, Kara M, Korkmaz A, Cay S, ... Topaloglu S, Aras D
J Cardiovasc Electrophysiol: 11 Jan 2020; epub ahead of print | PMID: 31930588
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Abstract

Pulmonary veins anatomical determinants of cooling kinetics during second generation cryoballoon ablation.

Gianluca B, Riccardo M, Alessandro R, Erwin S, ... Carlo A, Gian Battista C
Aim of the study
The aim of the study was to investigate the role of anatomical characteristics of the pulmonary veins (PV) determining cooling kinetics during second generation cryoballoon ablation (CbA).
Methods and results
we enrolled all consecutive patients who underwent CbA for symptomatic atrial fibrillation in our center from January 2019 to March 2019. All patients had complete computed tomography scans of the heart prior to the ablation. Anatomical characteristics were tested for prediction of a nadir temperature (NT)≤-48°C. Significant differences were noted among PV max diameter (20.8±2.8 vs. 18.5±2.5 mm; p<0.001); PV minimum diameter (15.2±3.0 vs. 13.0±3.1 mm; p<0.001); PV area (268.1±71.9 vs. 206.2±58.7 mm ; p<0.001); PV ovality (1.4±0.3 vs. 1.5±0.3; p=0.005) and PV trunk length (27.4±7.4 vs. 21.3±6.5 mm; p<0.001). A scoring system was created by assigning 1 point each ranging from 0 (best anatomical combination) to 5. In group with score of 0, 94.0% of the CbA could reach a NT≤-48°C whereas with a score of 5, only 29.0% (p<0.001). LIPV with short trunk length and acute angle of PV branch was significantly associated with warmer NT (11.8% satisfactory CbA; p=0.003). Regarding RIPV, trunk length (p=0.004), maximum diameter (p=0.044) and transverse angle (p=0.008) were independently associated with good NT.
Conclusions
anatomical PV features are associated with cooling kinetics and an anatomical score could predict lower NT during second generation CbA. Specific characteristics were identified for inferior PV. Although heart imaging is not mandatory prior CbA it can be a useful tool to predict cooling kinetics. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 13 Jan 2020; epub ahead of print
Gianluca B, Riccardo M, Alessandro R, Erwin S, ... Carlo A, Gian Battista C
J Cardiovasc Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31943519
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Impact:
Abstract

Chronic Dantrolene Treatment Does not Affect Hypertension, but Attenuates Sympathetic Stimulation Enhanced Atrial Fibrillation Inducibility in SHR.

Lee JS, Greco L, Migirov A, Li Y, Gerdes AM, Zhang Y
Background
Ryanodine receptor (RyR) dysfunction in skeletal muscle (RyR1) leads to malignant hyperthermia, and in cardiac muscle (RyR2) triggers cardiac arrhythmias. We hypothesized that RyR dysfunction in vascular smooth muscle could increase vascular resistance and hypertension, and may contribute to increased atrial fibrillation (AF) in hypertension. Thus, stabilizing RyR function with chronic dantrolene treatment may attenuate hypertension and AF inducibility in spontaneously hypertensive rats (SHR).
Methods
Male SHR (16 weeks-old) were randomized into vehicle- (n=10) and dantrolene-treated (10mg/kg/d, n=10) groups for 4-weeks. Wistar Kyoto (WKY, n=11) rats served as controls. Blood pressures (BP) were monitored before and during the 4-week treatment. After 4- week treatment, direct BP, echocardiography and hemodynamics were recorded. AF inducibility tests were performed in vivo at baseline and repeated under sympathetic stimulation (SS).
Results
Compared with WKY, SHR had significantly higher BP throughout the experimental period. Dantrolene treatment had no effect on BP levels in SHR (final systolic BP 212±9mmHg in vehicle group versus 208±16 mmHg in dantrolene group, p>0.05). AF inducibility was very low and not significantly different between 5-month old WKY and SHR at baseline. However, under SS, AF inducibility and duration were significantly increased in SHR (20% in WKY versus 60% in SHR-vehicle, p<0.05). Dantrolene treatment significantly attenuated AF inducibility under SS in SHR (60% in vehicle versus 20% in dantrolene, p<0.05).
Conclusions
Stabilizing RyR with chronic dantrolene treatment does not affect hypertension development in SHR. SHR has increased vulnerability to AF induction under SS, which can be attenuated with dantrolene treatment.

© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: [email protected]

Am J Hypertens: 14 Feb 2020; epub ahead of print
Lee JS, Greco L, Migirov A, Li Y, Gerdes AM, Zhang Y
Am J Hypertens: 14 Feb 2020; epub ahead of print | PMID: 32060500
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Impact:
Abstract

Performance of diagnostic criteria in patients clinically judged to have cardiac sarcoidosis: Is it time to regroup?

Ribeiro Neto ML, Jellis C, Hachamovitch R, Wimer A, ... Joyce E, Culver DA
Background
The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS.
Aims
To compare the 3 main available diagnostic criteria in patients clinically judged to have CS.
Methods
We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria.
Results
We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326).
Conclusions
A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 07 Feb 2020; 223:106-109
Ribeiro Neto ML, Jellis C, Hachamovitch R, Wimer A, ... Joyce E, Culver DA
Am Heart J: 07 Feb 2020; 223:106-109 | PMID: 32240829
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Impact:
Abstract

Ischaemic cardiomyopathy. Pathophysiological insights, diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology.

Cabac-Pogorevici I, Muk B, Rustamova Y, Kalogeropoulos A, Tzeis S, Vardas P

Ischaemic cardiomyopathy (ICM) represents an important cardiovascular condition associated with substantially increased morbidity and mortality. It is characterised from a broad spectrum of clinical manifestations and pathophysiological substrates and its diagnosis is based on the demonstration of significant left ventricular dysfunction in the context of significant epicardial coronary artery disease. Contemporary management aims at improving prognosis through evidence-based pharmacotherapy and device therapy, where indicated. Whilst the beneficial role of revascularisation remains clear in patients with strong indications such as those with symptoms and/or acute coronary syndromes, for those patients that are asymptomatic and suffer from stable ischaemic heart disease the impact of revascularisation on hard outcomes remains less well defined and currently its adoption is hampered by the lack of robust randomised data. The aim of this review is therefore to provide a constructive appraisal on the pathophysiology of ICM, the role of the various non-invasive imaging techniques in the diagnosis of ICM and the differentiation between viable and non-viable myocardium and finally discourse the potential role of revascularisation and contemporary device therapy in the management of patients with ICM.

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

Eur J Heart Fail: 04 Feb 2020; epub ahead of print
Cabac-Pogorevici I, Muk B, Rustamova Y, Kalogeropoulos A, Tzeis S, Vardas P
Eur J Heart Fail: 04 Feb 2020; epub ahead of print | PMID: 32020756
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Impact:
Abstract

Transvenous lead extraction after heart transplantation: How to avoid abandoned lead fragments.

Hahnel F, Pecha S, Bernhardt A, Barten MJ, ... Reichenspurner H, Hakmi S
Background
Many patients awaiting heart transplantation (HTX) have a cardiac implantable electronic device (CIED). Lead removal is often still a part of the HTX procedure. Abandoned lead fragments carry a risk for infections and prohibit MRI imaging. This study evaluated the concept of an elective lead management algorithm after HTX.
Methods and results
Between 2009 and 2018, 102 consecutive patients with previously implanted CIED underwent HTX. Lead removal by manual traction during HTX was performed in 74 patients until December 2014. Afterwards, treatment strategy was changed and 28 patients received elective lead extraction procedure in a hybrid OR using specialized extraction tools. 74 patients with 157 leads underwent lead extraction by manual traction during HTX. Mean lead age was 32.3±38.7 months. Postoperative X-ray revealed abandoned intravascular lead fragments in 31(41.9%) patients, resulting in a complete lead extraction rate of only 58.1%. The high rate of unsuccessful lead extractions led to the change in extraction strategy in 2015. Since then, HTX was performed in 28 CIED patients. In those patients, 64 leads with a mean lead age of 53.8±42.8 months were treated in an elective lead extraction procedure. No major or minor complications occurred during lead extraction. All leads could be removed completely, resulting in a procedural success rate of 100%.
Conclusion
Our results demonstrate that chronically implanted leads should be removed in an elective procedure, using appropriate extraction tools. This enables complete lead extraction, which reduces the infection risk in this patient population with necessity for permanent immunosuppressive therapy and allows further MRI surveillance. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 12 Feb 2020; epub ahead of print
Hahnel F, Pecha S, Bernhardt A, Barten MJ, ... Reichenspurner H, Hakmi S
J Cardiovasc Electrophysiol: 12 Feb 2020; epub ahead of print | PMID: 32052893
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Impact:
Abstract

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test.

Pugliese NR, Mazzola M, Fabiani I, Gargani L, ... Natali A, Dini FL
Aim
We combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) to identify early haemodynamic and metabolic alterations in patients with hypertension (HT) with and without heart failure with preserved ejection fraction (HFpEF).
Methods and results
Fifty stable HFpEF-HT outpatients (mean age 68 ± 14 years) on optimal medical therapy, 63 well-controlled HT subjects (mean age 63 ± 11 years) and 32 age and sex-matched healthy controls (mean age 59 ± 15 years) underwent a symptom-limited graded ramp bicycle CPET-ESE. The acquisition protocol included left ventricular cardiac output, global longitudinal strain, E/e\', peak oxygen consumption (VO ), non-invasive arterial-venous oxygen content difference (AVO diff) and lung ultrasound B-lines. There was a decline in peak VO from controls (24.4 ± 3 mL/min/kg) to HFpEF-HT (15.2 ± 2 mL/min/kg), passing through HT (18.7 ± 2 mL/min/kg; P < 0.0001). HFpEF-HT displayed a lower peak cardiac output (9.8 ± 0.9 L/min) compared to HT (12.6 ± 1.0 L/min; P = 0.02) and controls (13.3 ± 1.0 L/min; P = 0.01). Peak AVO diff was reduced in HFpEF-HT and HT (13.3 ± 2 and 13.5 ± 2 mL/dL vs. controls: 16.9 ± 2 mL/dL; P < 0.0001). A different left ventricular contractility was observed among groups, expressed as low-load global longitudinal strain (-16.8 ± 5% in HFpEF-HT, -18.2 ± 3% in HT, and 20.9 ± 3% in controls; P < 0.0001), and distribution of E/e\' and B-lines [HFpEF-HT: 13.7 ± 3 and 16, interquartile range (IQR) 10-22; HT: 9.5 ± 2 and 8, IQR 4-10; controls: 6.2 ± 2 and 0, IQR 0-2; P < 0.0001].
Conclusions
Reduced peak VO values in HT with and without HFpEF may be the result of decreased AVO diff. CPET-ESE can also identify mild signs of left ventricular systo-diastolic dysfunction and pulmonary congestion, promoting advances in personalized therapy.

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

Eur J Heart Fail: 15 Jan 2020; epub ahead of print
Pugliese NR, Mazzola M, Fabiani I, Gargani L, ... Natali A, Dini FL
Eur J Heart Fail: 15 Jan 2020; epub ahead of print | PMID: 31950651
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Impact:
Abstract

Association of Machine Learning-Derived Phenogroupings of Echocardiographic Variables with Heart Failure in Stable Coronary Artery Disease: The Heart and Soul Study.

Mishra RK, Tison GH, Fang Q, Scherzer R, Whooley MA, Schiller NB
Background
Many individual echocardiographic variables have been associated with heart failure (HF) in patients with stable coronary artery disease (CAD), but their combined utility for prediction has not been well studied.
Methods
Unsupervised model-based cluster analysis was performed by researchers blinded to the study outcome in 1,000 patients with stable CAD on 15 transthoracic echocardiographic variables. We evaluated associations of cluster membership with HF hospitalization using Cox proportional hazards regression analysis.
Results
The echo-derived clusters partitioned subjects into four phenogroupings: phenogroup 1 (n = 85) had the highest levels, phenogroups 2 (n = 314) and 3 (n = 205) displayed intermediate levels, and phenogroup 4 (n = 396) had the lowest levels of cardiopulmonary structural and functional abnormalities. Over 7.1 ± 3.2 years of follow-up, there were 198 HF hospitalizations. After multivariable adjustment for traditional cardiovascular risk factors, phenogroup 1 was associated with a nearly fivefold increased risk (hazard ratio [HR] = 4.8; 95% CI, 2.4-9.5), phenogroup 2 was associated with a nearly threefold increased risk (HR = 2.7; 95% CI, 1.4-5.0), and phenogroup 3 was associated with a nearly twofold increased risk (HR = 1.9; 95% CI, 1.0-3.8) of HF hospitalization, relative to phenogroup 4.
Conclusions
Transthoracic echocardiographic variables can be used to classify stable CAD patients into separate phenogroupings that differentiate cardiopulmonary structural and functional abnormalities and can predict HF hospitalization, independent of traditional cardiovascular risk factors.

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

J Am Soc Echocardiogr: 12 Jan 2020; epub ahead of print
Mishra RK, Tison GH, Fang Q, Scherzer R, Whooley MA, Schiller NB
J Am Soc Echocardiogr: 12 Jan 2020; epub ahead of print | PMID: 31948711
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Impact:
Abstract

Additional benefits of non-conventional modalities of cardiac resynchronization therapy using His bundle pacing.

Coluccia G, Vitale E, Corallo S, Aste M, ... Oddone D, Brignole M
Introduction
Dyssynchrony persists in many patients despite cardiac resynchronization therapy (CRT). Aim of this proof-of-concept study was to achieve better CRT, with a QRS approximating the normal width and axis, by using His bundle pacing and non-conventional pacing configurations.
Methods and results
In 20 patients with CRT indications, we performed an acute intra-patient comparison between conventional biventricular (CONV) and three non-conventional pacing modalities: His bundle pacing alone (HBP), His bundle and coronary sinus pacing (HBP+CS) and HBP+CS plus right ventricular pacing (TRIPLE). Electrical dyssynchrony was assessed by means of QRS width and axis; \"quasi-normal\" axis meant an R/S ratio ≥1 in leads I and V6 and ≤1 in V1. Mechanical dyssynchrony was assessed by speckle tracking echocardiography. QRS width was 153±18 ms on CONV, shortened to 137±16 ms on HBP+CS (p=0.001) and to 130±14 ms on TRIPLE (p=0.001), while it remained unchanged on HBP (159±32 ms, p=0.17). The rate of patients with \"quasi-normal\" axis was 5% on CONV, and increased to 90% on HBP (p=0.0001), to 63% on HBP+CS (p=0.001) and to 44% on TRIPLE (p=0.02). On radial strain analysis, the time-to-peak difference between antero-septal and postero-lateral segments was 143±116 ms on CONV, shortened to 121±127 ms on HBP (p=0.79), to 67±70 ms on HBP+CS (p=0.02) and to 76±55 ms on TRIPLE (p=0.05). On discharge, HBP was chosen in 15% of patients, HBP+CS in 55% and TRIPLE in 30%; CONV was never chosen.
Conclusion
Non-conventional modalities of CRT provide acute additional electrical and mechanical resynchronization. An inter-patient variability exists. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 18 Jan 2020; epub ahead of print
Coluccia G, Vitale E, Corallo S, Aste M, ... Oddone D, Brignole M
J Cardiovasc Electrophysiol: 18 Jan 2020; epub ahead of print | PMID: 31957086
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Impact:
Abstract

Pre-procedural Computed Tomography Before Cardiac Implanted Electronic Device Lead Extraction: Indication, Technique, and Approach to Interpretation.

Lewis R, Ehieli WL, Hegland DD, Pokorney SD, ... Hurwitz Koweek LM, Piccini JP

Cardiac implantable electronic devices (CIED) frequently need to be extracted due to infection, hardware failure, and other causes. Extraction of the CIED is typically performed using percutaneous methods. While these procedures are mostly performed without incident there is a small risk of significant complications. Dedicated imaging pre CEID removal to include the central veins and heart with multidetector computed tomography (MDCT) can be utilized to evaluate the lead course and termination, integrity of the central veins and cardiac chambers, and identify potential complications that may alter the lead extraction procedure as well as reimplantation of subsequent leads. Indications for preprocedural imaging, technique of dedicated preprocedural lead extraction MDCT, and the approach to interpretation of the images is discussed in this review. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 13 Jan 2020; epub ahead of print
Lewis R, Ehieli WL, Hegland DD, Pokorney SD, ... Hurwitz Koweek LM, Piccini JP
J Cardiovasc Electrophysiol: 13 Jan 2020; epub ahead of print | PMID: 31943485
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Impact:
Abstract

Use of a clot aspiration system during transvenous lead extraction.

Richardson TD, Lugo RM, Crossley GH, Ellis CR
Introduction
The optimal approach to the extraction of leads with large vegetations remains uncertain.
Methods
High-risk patients with lead associated vegetations undergoing device extraction at Vanderbilt Hospital with concomitant use of the Penumbra Aspiration System (Penumbra Inc, Alameda, CA) are described. An 8.5 Fr Agilis NXT (Abbott Inc, St. Paul, MN) was advanced to the right atrium, through which a Penumbra Indigo Cat-8 catheter was advanced. Using intracardiac echocardiography, the Penumbra was positioned directly on the vegetation, suction was applied until adherent, and the Indigo catheter and Agilis sheath were then removed en-bloc and aspirated debris flushed out. This was repeated until debulking was considered successful.
Results
Eight cases were performed. The median vegetation size was 2 cm. Pathogens were Enterococcus, Staphylococcus, Candida, Cutibacterium, and Enterobacter. In seven of eight cases, aspiration successfully reduced vegetations to less than 1 cm before successful percutaneous cardiac implantable electronic device removal. One patient underwent surgical removal via thoracotomy. There were no acute complications related to the Penumbra catheter. Three patients had CT evidence of small pulmonary emboli postprocedure. The length of stay was 3 to 27 days. One patient died on POD 1 of refractory ventricular tachycardia unrelated to the procedure. One patient died of ongoing sepsis 2 weeks postextraction.
Conclusions
The Penumbra Indigo Aspiration system can be useful for vegetation debulking before transvenous lead extraction.

© 2020 Wiley Periodicals, Inc.

J Cardiovasc Electrophysiol: 29 Jan 2020; epub ahead of print
Richardson TD, Lugo RM, Crossley GH, Ellis CR
J Cardiovasc Electrophysiol: 29 Jan 2020; epub ahead of print | PMID: 32003095
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Impact:
Abstract

The use of intracardiac echocardiography (ICE) catheters in endocardial ablation of cardiac arrhythmia: meta-analysis of efficiency, effectiveness, and safety outcomes.

Goya M, Frame D, Gache L, Ichishima Y, ... Laura Goldstein JD, Hsiao Yu Lee S
Aims
Optimal use of intracardiac echocardiography (ICE) may reduce fluoroscopy time and procedural complications during endocardial ablation of cardiac arrhythmias. Due to limited evidence in this area, we conducted the first systematic literature review and meta-analysis to evaluate outcomes associated with the use of ICE.
Methods and results
Studies reporting the use of ICE during ablation procedures vs. without ICE were searched using PubMed/MEDLINE. A meta-analysis was performed on the 19 studies (2,186 patients) meeting inclusion criteria, collectively representing a broad range of arrhythmia mechanisms. Use of ICE was associated with significant reductions in fluoroscopy time (Hedges\' g -1.06; 95% confidence interval [CI] -1.81 to -0.32; p < 0.01), fluoroscopy dose (Hedges\' g -1.27; 95% CI -1.91 to -0.62; p < 0.01), and procedure time (Hedges\' g -0.35; 95% CI -0.64 to -0.05; p = 0.02) vs. ablation without ICE. A 6.95 minute reduction in fluoroscopy time and a 15.2 minute reduction in procedure time was observed between the ICE vs. non-ICE groups. These efficiency gains were not associated with any decreased effectiveness or safety. Sensitivity analyses limiting studies to an Atrial Fibrillation (AF) only population yielded similar results to the main analysis.
Conclusion
Use of ICE in ablation of cardiac arrhythmias is associated with significantly lower fluoroscopy time, fluoroscopy dose, and shorter procedure time vs. ablation without ICE. These efficiency improvements did not compromise the clinical effectiveness or safety of the procedure. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 23 Jan 2020; epub ahead of print
Goya M, Frame D, Gache L, Ichishima Y, ... Laura Goldstein JD, Hsiao Yu Lee S
J Cardiovasc Electrophysiol: 23 Jan 2020; epub ahead of print | PMID: 31976603
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Impact:
Abstract

Left Atrial Strain Correlates with Elevated Filling Pressures in Pediatric Heart Transplantation Recipients.

Loar RW, Pignatelli RH, Morris SA, Colquitt JL, ... Denfield SW, Tunuguntla HP
Background
Noninvasive assessment of diastolic function in pediatric heart transplantation (PHTx) patients is important for monitoring of rejection, cardiac allograft vasculopathy, and nonspecific graft failure. We hypothesized that left atrial strain (LAS) would correlate with pulmonary capillary wedge pressure (PCWP) and that cutoff values to identify elevated left ventricular (LV) filling pressure could be derived for clinical practice and future testing.
Methods
This was a secondary analysis of a prospectively collected cohort of PHTx patients undergoing same-day cardiac catheterization with biopsy and transthoracic echo. There were 70 patients with 85 clinical encounters. Traditional mitral inflow Doppler, LAS, LV diastolic strain and strain rate, and ratios for mitral E to LV diastolic strain and strain rate were assessed. Correlation with PCWP was performed, and receiver operator characteristic curves were generated for an elevated mean PCWP, acute rejection, and cardiac allograft vasculopathy.
Results
Decreased LAS during the atrial reservoir phase (Ɛres) correlated with higher invasively measured PCWP (r = -0.40, P < .001). An Ɛres cutoff of 14.5% had good discriminatory ability for an elevated PCWP (sensitivity 75%, specificity 82%), and Ɛres > 22.0% had 100% negative predictive value; Ɛres was superior to other measures of diastolic function. Subanalyses for recent acute rejection (n = 9) showed good discriminatory ability for Ɛres of 14.5% (sensitivity 89%, specificity 74%).
Conclusions
LAS correlates with invasively measured PCWP and can identify elevated pressures better than traditional and other advanced diastolic function parameters. Use of LAS in PHTx patients may aid in noninvasive monitoring for rejection and nonspecific graft dysfunction.

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

J Am Soc Echocardiogr: 23 Jan 2020; epub ahead of print
Loar RW, Pignatelli RH, Morris SA, Colquitt JL, ... Denfield SW, Tunuguntla HP
J Am Soc Echocardiogr: 23 Jan 2020; epub ahead of print | PMID: 31987750
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Impact:
Abstract

Positron Emission Tomography Absolute Stress Myocardial Blood Flow for Risk Stratification in Nonischemic Cardiomyopathy.

Middour TG, Rosenthal TM, Abi-Samra FM, Bernard ML, ... Bober RM, Morin DP
Introduction
Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM.
Methods
In this pilot study, we prospectively followed patients with NICM (LVEF ≤35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (i.e., the primary prevention population).
Results
We followed 37 patients (60±14 years, 46% male) for 41±23 months. The median sMBF was 1.56 mL/g/min [IQR 1.00-1.82]. Lower sMBF predicted VA, both in the whole population (HR for each 0.1 mL/g/min increase: 0.84, P=0.015) and in the primary prevention subset (n=27; HR for each 0.1 mL/g/min increase: 0.81, P=0.049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P=0.004) and in the primary prevention subset (P=0.046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs. 13% among high-flow patients, and 39% vs. 8% among primary-prevention patients. sMBF did not predict all-cause mortality.
Conclusions
In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision-making regarding ICD implantation. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

J Cardiovasc Electrophysiol: 15 Feb 2020; epub ahead of print
Middour TG, Rosenthal TM, Abi-Samra FM, Bernard ML, ... Bober RM, Morin DP
J Cardiovasc Electrophysiol: 15 Feb 2020; epub ahead of print | PMID: 32064730
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Impact:
Abstract

Blood Speckle-Tracking Based on High-Frame Rate Ultrasound Imaging in Pediatric Cardiology.

Nyrnes SA, Fadnes S, Wigen MS, Mertens L, Lovstakken L
Background
Flow properties play an important role in cardiac function, remodeling, and morphogenesis but cannot be displayed in detail with today\'s echocardiographic techniques. The authors hypothesized that blood speckle-tracking (BST) could visualize and quantify flow patterns. The aim of this study was to determine the feasibility, accuracy, and potential clinical applications of BST in pediatric cardiology.
Methods
BST is based on high-frame rate ultrasound, using a combination of plane-wave imaging and parallel receive beamforming. Pattern-matching techniques are used to quantify blood speckle motion. Accuracy of BST velocity measurements was validated using a rotating phantom and by comparing BST-derived inflow velocities with pulsed-wave Doppler obtained in the left ventricles of healthy control subjects. To test clinical feasibility, 102 subjects (21 weeks to 11.5 years of age) were prospectively enrolled, including healthy fetuses (n = 4), healthy control subjects (n = 51), and patients with different cardiac diseases (n = 47).
Results
The phantom data showed a good correlation (r = 0.95, with a tracking quality threshold of 0.4) between estimated BST velocities and reference velocities down to a depth of 8 cm. There was a good correlation (r = 0.76) between left ventricular inflow velocity measured using BST and pulsed-wave Doppler. BST displayed lower velocities (mean ± SD, 0.59 ± 0.14 vs 0.82 ± 0.21 m/sec for pulsed-wave Doppler). However, the velocity amplitude in BST increases with reduced smoothing. The clinical feasibility of BST was high, as flow patterns in the area of interest could be visualized in all but one case (>99%).
Conclusions
BST is highly feasible in fetal and pediatric echocardiography and provides a novel approach for visualizing blood flow patterns. BST provides accurate velocity measurements down to 8 cm, but compared with pulsed-wave Doppler, BST displays lower velocities. Studying blood flow properties may provide novel insights into the pathophysiology of pediatric heart disease and could become an important diagnostic tool.

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

J Am Soc Echocardiogr: 23 Jan 2020; epub ahead of print
Nyrnes SA, Fadnes S, Wigen MS, Mertens L, Lovstakken L
J Am Soc Echocardiogr: 23 Jan 2020; epub ahead of print | PMID: 31987749
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Impact:
Abstract

Association of Right Ventricular Longitudinal Strain with Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.

Medvedofsky D, Koifman E, Jarrett H, Miyoshi T, ... Waksman R, Asch FM
Background
Conventional right ventricular (RV) echocardiographic measurements of systolic function (SF) have demonstrated conflicting results when their association with long-term outcomes after transcatheter aortic valve replacement (TAVR) is evaluated. RV free-wall (FW) longitudinal strain (LS) is a novel, single parameter to measure RV SF and may provide a better evaluation than fractional area change, tricuspid annular plane systolic excursion, and myocardial velocity (S\'). The value of RV FW LS in patients undergoing TAVR and its association with 1-year mortality are unknown. The aim of this study was to test the hypothesis that RV FW LS would be associated with 1-year all-cause mortality in patients undergoing TAVR.
Methods
Consecutive patients who underwent TAVR between 2007 and 2014 in whom RV FW LS was measurable were included; a subgroup that had 1-year follow-up echocardiographic evaluation of RV FW LS was analyzed. FW LS was derived from speckle-tracking analyses. The standard reference was determined as normal or impaired RV SF, the latter defined as the presence of ≥50% of tricuspid annular plane systolic excursion < 1.7 cm, S\' < 9.5 cm/sec, and fractional area change < 35%. Cox proportional-hazards regression analysis was used to assess the association of RV FW LS with 1-year all-cause mortality.
Results
Of 612 patients, 334 were included for RV FW LS analysis on pre-TAVR echocardiography (feasibility 55%); exclusion criteria included atrial fibrillation (n = 92 [15%]), pacemaker (n = 73 [12%]), and poor image quality (n = 113 [18%]). Baseline impaired RV SF was present in 19% of cases. RV FW LS did not change significantly at 1-year follow-up, in both the groups with baseline impaired and normal function. Cox regression analysis showed that RV FW LS was associated with all-cause mortality at 1 year (hazard ratio, 1.06; 95% CI, 1.01-1.11). For each unit increase in RV FW LS, there was a 6% higher risk for 1-year mortality.
Conclusions
In a high-risk TAVR population, RV FW LS should be considered a single echocardiographic parameter for the assessment of RV SF. When measurable, RV FW LS is associated with all-cause mortality at 1 year after TAVR.

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

J Am Soc Echocardiogr: 03 Feb 2020; epub ahead of print
Medvedofsky D, Koifman E, Jarrett H, Miyoshi T, ... Waksman R, Asch FM
J Am Soc Echocardiogr: 03 Feb 2020; epub ahead of print | PMID: 32033789
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