Topic: Journal Club Selection

Abstract

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

Van Mieghem NM, Unverdorben M, Hengstenberg C, Möllmann H, ... Dangas GD, ENVISAGE-TAVI AF Investigators
Background
The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.
Methods
We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding.
Results
A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11).
Conclusions
In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 27 Aug 2021; epub ahead of print
Van Mieghem NM, Unverdorben M, Hengstenberg C, Möllmann H, ... Dangas GD, ENVISAGE-TAVI AF Investigators
N Engl J Med: 27 Aug 2021; epub ahead of print | PMID: 34449183
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Impact:
Abstract

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

Anker SD, Butler J, Filippatos G, Ferreira JP, ... Packer M, EMPEROR-Preserved Trial Investigators
Background
Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.
Methods
In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.
Results
Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin.
Conclusions
Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 26 Aug 2021; epub ahead of print
Anker SD, Butler J, Filippatos G, Ferreira JP, ... Packer M, EMPEROR-Preserved Trial Investigators
N Engl J Med: 26 Aug 2021; epub ahead of print | PMID: 34449189
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Impact:
Abstract

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.

Weinreich DM, Sivapalasingam S, Norton T, Ali S, ... Yancopoulos GD, Trial Investigators
Background
In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.
Methods
In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated.
Results
Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.
Conclusions
REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 28 Sep 2021; epub ahead of print
Weinreich DM, Sivapalasingam S, Norton T, Ali S, ... Yancopoulos GD, Trial Investigators
N Engl J Med: 28 Sep 2021; epub ahead of print | PMID: 34587383
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Abstract

Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

Korley FK, Durkalski-Mauldin V, Yeatts SD, Schulman K, ... Callaway CW, SIREN-C3PO Investigators
Background
Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.
Methods
In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.
Results
A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.
Conclusions
The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

Copyright © 2021 Massachusetts Medical Society.

N Engl J Med: 17 Aug 2021; epub ahead of print
Korley FK, Durkalski-Mauldin V, Yeatts SD, Schulman K, ... Callaway CW, SIREN-C3PO Investigators
N Engl J Med: 17 Aug 2021; epub ahead of print | PMID: 34407339
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Abstract

Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms.

Liu X, Guo JW, Lin XC, Tuo YH, ... Zhou JG, Liang SJ
Aims
Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin-ASK1 pathway, not the classical calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis.
Methods and results
Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages.
Conclusion
Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 26 Sep 2021; epub ahead of print
Liu X, Guo JW, Lin XC, Tuo YH, ... Zhou JG, Liang SJ
Eur Heart J: 26 Sep 2021; epub ahead of print | PMID: 34570211
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Abstract

Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.

Haghikia A, Zimmermann F, Schumann P, Jasina A, ... Haghikia A, Landmesser U
Aims
Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism.
Methods and results
Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels.
Conclusion
Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 30 Sep 2021; epub ahead of print
Haghikia A, Zimmermann F, Schumann P, Jasina A, ... Haghikia A, Landmesser U
Eur Heart J: 30 Sep 2021; epub ahead of print | PMID: 34597388
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Impact:
Abstract

Troponin-Guided Coronary Computed Tomographic Angiography After Exclusion of Myocardial Infarction.

Lee KK, Bularga A, O\'Brien R, Ferry AV, ... Gray AJ, Mills NL
Background
Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events.
Objectives
This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded.
Methods
This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge.
Results
Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA.
Conclusions
In patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Oct 2021; 78:1407-1417
Lee KK, Bularga A, O'Brien R, Ferry AV, ... Gray AJ, Mills NL
J Am Coll Cardiol: 04 Oct 2021; 78:1407-1417 | PMID: 34593122
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Impact:
Abstract

Early invasive coronary angiography and acute ischaemic heart failure outcomes.

Kosyakovsky LB, Austin PC, Ross HJ, Wang X, ... Spertus JA, Lee DS
Aims 
While myocardial ischaemia plays a major role in the pathogenesis of heart failure (HF), the indications for coronary angiography during acute HF are not established. We determined the association of early coronary angiography during acute HF hospitalization with 2-year mortality, cardiovascular death, HF readmissions, and coronary revascularization.
Methods and results 
In a two-stage sampling process, we identified acute HF patients who presented to 70 emergency departments in Ontario (April 2010 to March 2013) and determined whether they underwent early coronary angiography within 14 days after presentation using administrative databases. After clinical record review, we defined a cohort with acute ischaemic HF as patients with at least one factor suggesting underlying ischaemic heart disease, including previous myocardial infarction, troponin elevation, or angina on presentation. We oversampled patients undergoing angiography. We used inverse-probability-of-treatment weighting (IPTW) to adjust for baseline differences. Of 7239 patients with acute HF, 2994 met inclusion criteria [median age 75 (interquartile range 65-83) years; 40.9% women]. Early angiography was performed in 1567 patients (52.3%) and was associated with lower all-cause mortality [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.61-0.90, P = 0.002], cardiovascular death (HR 0.72, 95% CI 0.56-0.93, P = 0.012), and HF readmissions (HR 0.84, 95% CI 0.71-0.99, P = 0.042) after IPTW. Those undergoing early angiography experienced higher rates of percutaneous coronary intervention (HR 2.58, 95% CI 1.73-3.86, P < 0.001) and coronary artery bypass grafting (HR 2.94, 95% CI 1.75-4.93, P < 0.001) within 2 years.
Conclusions 
Early coronary angiography was associated with lower all-cause mortality, cardiovascular death, HF readmissions, and higher rates of coronary revascularization in acute HF patients with possible ischaemia.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 20 Sep 2021; 42:3756-3766
Kosyakovsky LB, Austin PC, Ross HJ, Wang X, ... Spertus JA, Lee DS
Eur Heart J: 20 Sep 2021; 42:3756-3766 | PMID: 34331056
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Abstract

3\' untranslated region of Ckip-1 inhibits cardiac hypertrophy independently of its cognate protein.

Zhao Y, Ling S, Li J, Zhong G, ... Chang YZ, Li Y
Aims
3\' untranslated region (3\' UTR) of mRNA is more conserved than other non-coding sequences in vertebrate genomes, and its sequence space has substantially expanded during the evolution of higher organisms, which substantiates their significance in biological regulation. However, the independent role of 3\' UTR in cardiovascular disease was largely unknown.
Methods and results
Using bioinformatics, RNA fluorescent in situ hybridization and quantitative real-time polymerase chain reaction, we found that 3\' UTR and coding sequence regions of Ckip-1 mRNA exhibited diverse expression and localization in cardiomyocytes. We generated cardiac-specific Ckip-1 3\' UTR overexpression mice under wild type and casein kinase 2 interacting protein-1 (CKIP-1) knockout background. Cardiac remodelling was assessed by histological, echocardiography, and molecular analyses at 4 weeks after transverse aortic constriction (TAC) surgery. The results showed that cardiac Ckip-1 3\' UTR significantly inhibited TAC-induced cardiac hypertrophy independent of CKIP-1 protein. To determine the mechanism of Ckip-1 3\' UTR in cardiac hypertrophy, we performed transcriptome and metabolomics analyses, RNA immunoprecipitation, biotin-based RNA pull-down, and reporter gene assays. We found that Ckip-1 3\' UTR promoted fatty acid metabolism through AMPK-PPARα-CPT1b axis, leading to its protection against pathological cardiac hypertrophy. Moreover, Ckip-1 3\' UTR RNA therapy using adeno-associated virus obviously alleviates cardiac hypertrophy and improves heart function.
Conclusions
These findings disclose that Ckip-1 3\' UTR inhibits cardiac hypertrophy independently of its cognate protein. Ckip-1 3\' UTR is an effective RNA-based therapy tool for treating cardiac hypertrophy and heart failure.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J: 20 Sep 2021; 42:3786-3799
Zhao Y, Ling S, Li J, Zhong G, ... Chang YZ, Li Y
Eur Heart J: 20 Sep 2021; 42:3786-3799 | PMID: 34347073
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Abstract

Stress Cardiac Magnetic Resonance Myocardial Perfusion Imaging: JACC Review Topic of the Week.

Patel AR, Salerno M, Kwong RY, Singh A, Heydari B, Kramer CM
Stress cardiovascular magnetic resonance imaging (CMR) is a cost-effective, noninvasive test that accurately assesses myocardial ischemia, myocardial viability, and cardiac function without the need for ionizing radiation. There is a large body of literature, including randomized controlled trials, validating its diagnostic performance, risk stratification capabilities, and ability to guide appropriate use of coronary intervention. Specifically, stress CMR has shown higher diagnostic sensitivity than single-photon emission computed tomography imaging in detecting angiographically significant coronary artery disease. Stress CMR is particularly valuable for the evaluation of patients with moderate to high pretest probability of having stable ischemic heart disease and for patients known to have challenging imaging characteristics, including women, individuals with prior revascularization, and those with left ventricular dysfunction. This paper reviews the basics principles of stress CMR, the data supporting its clinical use, the added-value of myocardial blood flow quantification, and the assessment of myocardial function and viability routinely obtained during a stress CMR study.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 18 Oct 2021; 78:1655-1668
Patel AR, Salerno M, Kwong RY, Singh A, Heydari B, Kramer CM
J Am Coll Cardiol: 18 Oct 2021; 78:1655-1668 | PMID: 34649703
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Abstract

Clinical Risk Prediction in Patients With Left Ventricular Myocardial Noncompaction.

Casas G, Limeres J, Oristrell G, Gutierrez-Garcia L, ... Ferreira-González I, Rodríguez-Palomares JF
Background
Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis.
Objectives
This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up.
Methods
This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality.
Results
A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up.
Conclusions
LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Aug 2021; 78:643-662
Casas G, Limeres J, Oristrell G, Gutierrez-Garcia L, ... Ferreira-González I, Rodríguez-Palomares JF
J Am Coll Cardiol: 16 Aug 2021; 78:643-662 | PMID: 34384546
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Abstract

Polymorphic Ventricular Tachycardia: Terminology, Mechanism, Diagnosis, and Emergency Therapy.

Viskin S, Chorin E, Viskin D, Hochstadt A, Schwartz AL, Rosso R
Polymorphic ventricular tachyarrhythmias are highly lethal arrhythmias. Several types of polymorphic ventricular tachycardia have similar electrocardiographic characteristics but have different modes of therapy. In fact, medications considered the treatment of choice for one form of polymorphic ventricular tachycardia, are contraindicated for the other. Yet confusion about terminology, and thus diagnosis and therapy, continues. We present an in-depth review of the different forms of polymorphic ventricular tachycardia and propose a practical step-by-step approach for distinguishing these malignant arrhythmias.



Circulation: 06 Sep 2021; 144:823-839
Viskin S, Chorin E, Viskin D, Hochstadt A, Schwartz AL, Rosso R
Circulation: 06 Sep 2021; 144:823-839 | PMID: 34491774
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Abstract

Screening of Native Valvular Heart Disease using a Pocket-Sized Transthoracic Echocardiography Device.

Kikoïne J, Hauguel-Moreau M, Hergault H, Aidan V, ... Szymanski C, Mansencal N
Aims
We assessed the performance of pocket-sized transthoracic echocardiography (pTTE) compared to standard transthoracic echocardiography (sTTE) and auscultation for an early screening of valvular heart disease (VHD). Early diagnosis of significant VHD is a real challenge, and enables appropriate follow-up and implementation of the best therapeutic strategy.
Methods
STTE, pTTE and auscultation were performed by three different experienced physicians in 284 unselected patients. All cases of VHD detected by each of these three techniques were noted. sTTE was the gold standard. Each physician performed one examination and was blinded to the results of other exams.
Results
We diagnosed a total of 301 VHD cases with a large predominance of regurgitant lesions: 269 (89.3%) of regurgitant VHD and 32 (10.7%) of stenotic VHD. pTTE was highly sensitive (85.7%) and specific (97.9%) for screening VHD, while auscultation detected only 54.1%. All significant VHD cases (at least mild severity) were detected by pTTE. The weighted Kappa between pTTE and sTTE for the assessment of mitral regurgitation was 0.71 (95% CI, 0.70-0.72), indicating good agreement. The weighted Kappa between pTTE and sTTE for the assessment of aortic regurgitation and aortic stenosis was 0.97 (95% CI, 0.96-0.98) and 0.98 (95% CI, 0.97-0.99), respectively, indicating excellent agreement.
Conclusion
PTTE performed by physicians with a level III competency in echocardiography is reliable for identifying significant VHD and should be proposed as a new screening tool.

Copyright © 2021. Published by Elsevier Inc.

J Am Soc Echocardiogr: 26 Aug 2021; epub ahead of print
Kikoïne J, Hauguel-Moreau M, Hergault H, Aidan V, ... Szymanski C, Mansencal N
J Am Soc Echocardiogr: 26 Aug 2021; epub ahead of print | PMID: 34461249
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Abstract

Dynamic Systolic Changes in Tricuspid Regurgitation Vena Contracta Size and Proximal Isovelocity Surface Area in Hypoplastic Left Heart Syndrome: A Three-Dimensional Color Doppler Echocardiographic Study.

Li L, Colen TM, Jani V, Barnes BT, ... Danford DA, Kutty S
Background
The aims of this study were to investigate the dynamic changes in the vena contracta (VC) and proximal isovelocity surface area (PISA) through systole in patients with hypoplastic left heart syndrome and tricuspid regurgitation and to identify the stage of systole (early, mid, or late) in which VC and PISA radius are optimal.
Methods
Twenty-eight patients with hypoplastic left heart syndrome were prospectively studied using continuous two-dimensional (2D) and three-dimensional (3D) echocardiography. Two-dimensional VC width, 3D VC area, and PISA radii (2D and 3D) were measured frame by frame throughout systole. The maximal 2D VC width, 3D VC area, and PISA radii in the first, middle, and last thirds of systole were compared, and correlations were explored with 3D tricuspid annular areas, right atrial volumes, and right ventricular volumes.
Results
In all, 35 data sets that met inclusion criteria were analyzed. On frame-by-frame analysis, maximal 2D VC width and 3D VC area were found in the first third of systole in 17% and 20% of studies, in the second third in 34% and 31%, and in the final third in 49% and 49%. Similarly, the maximal 2D and 3D PISA radii were found in the first third of systole in 26% and 17% of studies, in the second third in 28% and 34%, and in the final third in 46% and 49%.
Conclusions
In hypoplastic left heart syndrome, detailed temporal analysis of tricuspid regurgitation-associated VC and PISA by 2D and 3D echocardiography reveals no reliable pattern predicting when in systole these parameters peak. Frame-by-frame measurement is necessary for identification of maximal VC and PISA radius on 2D and 3D color Doppler echocardiography because the severity of tricuspid regurgitation could be underestimated because of temporal variability in VC and PISA.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 30 Jul 2021; 34:877-886
Li L, Colen TM, Jani V, Barnes BT, ... Danford DA, Kutty S
J Am Soc Echocardiogr: 30 Jul 2021; 34:877-886 | PMID: 33753189
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Abstract

Three-Dimensional Echocardiographic Left Atrial Appendage Volumetric Analysis.

Meltzer SN, Phatak PM, Fazlalizadeh H, Chang I, ... Kumar P, Medvedofsky D
Background
Left atrial appendage (LAA) echocardiographic assessment is difficult because of the complex shape and relatively small size of the LAA. Three-dimensional (3D) echocardiographic imaging can overcome the limitations of two-dimensional imaging. Pulsed-wave Doppler is the only currently standard LAA functional parameter. The aim of this study was to test a new approach for 3D echocardiographic volumetric analysis to obtain LAA ejection fraction (EF), its size and shape.
Methods
Transesophageal two-dimensional and 3D LAA images were prospectively obtained in 159 consecutive patients. LAA volumes were measured from 3D echocardiographic images using available software. Pulsed-wave Doppler was considered the reference value for LAA function and was used for comparison with LAA EF. Comparison with cardiac computed tomography was performed in a subgroup of 32 patients. Comparisons included linear regression and Bland-Altman analyses. Repeated measurements were performed to assess measurement variability.
Results
Nine patients were excluded because of suboptimal image quality (94% feasibility). Three-dimensional LAA calculated EF was in good agreement with LAA pulsed-wave measurements. Three-dimensional morphologic evaluation showed that 43% of the patients had \"chicken wing,\" 33% \"cactus,\" 19% \"windsock,\" and 5% cauliflower shapes. At the time of data acquisition, patients with atrial fibrillation had nonsignificantly larger LAA end-systolic and end-diastolic volumes, leading to lower calculated EFs. Three-dimensional echocardiographic LAA end-systolic volumes were in good agreement with cardiac computed tomography (r = 0.75), with small biases (mean, -2.5 ± 3.9 ml). Reproducibility was better for larger LAA volumes.
Conclusions
A novel 3D echocardiographic approach can determine the geometry, size, and function of the LAA. A new parameter, LAA EF, provides functional quantitation.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 30 Aug 2021; 34:987-995
Meltzer SN, Phatak PM, Fazlalizadeh H, Chang I, ... Kumar P, Medvedofsky D
J Am Soc Echocardiogr: 30 Aug 2021; 34:987-995 | PMID: 33775733
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Abstract

The evolving role of cardiac imaging in patients with myocardial infarction and non-obstructive coronary arteries.

Montone RA, Jang IK, Beltrame JF, Sicari R, ... Bucciarelli-Ducci C, Crea F
Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical conundrum accounting for about 6%-8% of all acute MI who are referred for coronary angiography. Current guidelines and consensus documents recommend that these patients are appropriately diagnosed, uncovering the causes of MINOCA, so that specific therapies can be prescribed. Indeed, there are a variety of causes that can result in this clinical condition, and for this reason diagnostic cardiac imaging has an emerging critical role in the assessment of patients with suspected or confirmed MINOCA. In last years, different cardiac imaging techniques have been evaluated in this context, and the comprehension of their strengths and limitations is of the utmost importance for their effective use in clinical practice. Moreover, recent evidence is clearly suggesting that a multimodality cardiac imaging approach, combining different techniques, seems to be crucial for a proper management of MINOCA. However, great variability still exists in clinical practice in the management of patients with suspected MINOCA, also depending on the availability of diagnostic tools and local expertise. Herein, we review the current knowledge supporting the use of different cardiac imaging techniques in patients with MINOCA, underscoring the importance of a comprehensive multimodality cardiac imaging approach and proposing a practical diagnostic algorithm to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients.

Copyright © 2018. Published by Elsevier Inc.

Prog Cardiovasc Dis: 29 Sep 2021; epub ahead of print
Montone RA, Jang IK, Beltrame JF, Sicari R, ... Bucciarelli-Ducci C, Crea F
Prog Cardiovasc Dis: 29 Sep 2021; epub ahead of print | PMID: 34600948
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This program is still in alpha version.