Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]

Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]

Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]

Nancy M

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

BackgroundClonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. MethodsWe used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case–control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls. To assess causality, we perturbed the function of Tet2, the second most commonly mutated gene linked to clonal hematopoiesis, in the hematopoietic cells of atherosclerosis-prone mice. ResultsIn nested case–control analyses from two prospective cohorts, carriers of CHIP had a risk of c...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1701719

Clonal Hematopoiesis and risk of atherosclerotic cardiovascular disease

Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10 − 20 ), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10 − 10 ). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10 − 6 ). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)

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Loss-of-function mutations in APOC3, triglycerides, and coronary disease

Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia

A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2012.07.013

/pdf/2012-accf-aha-acp-aats-pcna-scai-sts-guideline-for-the-3rcj2i2kf5.pdf

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

Background—We investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state. Methods and Results—This nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of <45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A &bgr;-fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction. Conclusions—This study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it.

https://air.unimi.it/bitstream/2434/53671/5/Circulation%20su%20infarti.pdf

No evidence of association between prothrombotic gene Polymorphisms and the development of acute myocardial infarction at a young age


 
 
 Right ventricular (RV) systolic function is an important predictor of prognosis in heart failure (HF). Several RV echocardiographic functional parameters have been described as sensitive prognostic markers.
 
 
 
 To compare the predictive value of different RV systolic echocardiographic parameters in patients with HF.
 
 
 
 One hundred and sixty patients with stable HF and left ventricular ejection fraction (LV EF) <45% were assessed for the following: (1) tricuspid annular plane systolic excursion (TAPSE), (2) RV fractional area (RVFA), (3) tissue Doppler-derived RV peak systolic velocity (PSVtdi), (4) RV free wall longitudinal 2D-strain (RVFWS); and (5) 3D-RVEF. The primary endpoint was death and/or HF-hospitalization.
 
 
 
 During a mean follow-up of 16.9±10 months, 35 patients reached the primary endpoint. Each of the RV echocardiographic parameters was significantly associated with outcome at univariable analysis. After adjusting for age, eGFR, logNTproBNP, LVEF, restrictive filling pattern, pulmonary artery systolic pressure, and RV end-diastolic volume, by Lasso Cox multivariable analysis, RVFWS (HR 1.09, 95%CI: 1.02-1.18, P=0.0093) and 3D-RVEF (HR 0.95, 95%CI: 0.91-0.99, P=0.0076) remained the only parameters independently associated with outcome with a cut-off of -18.6% and 43.6% respectively, without any difference in C-statistic between the two models (0.826 versus 0.812, p=0.3255).
 
 
 
 RVFWS and 3D-RVEF are strong independent predictors of outcome in HF and appear to be superior to other standard RV systolic echocardiographic parameters.


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235 comparison of the prognostic relevance of different echocardiographic parameters of right ventricular systolic function in chronic heart failure


 
 
 Left atrial appendage (LAA) is a finger-like muscular extension of the left atrium (LA). It acts as blood reservoir, modulates LA pressure and elicits adaptive responses to stress. Several LAA shapes and variants have been described. We report a case of congenital absence of LAA diagnosed by transesophageal echocardiography (TEE) and confirmed by computed tomography (CT).
 
 
 
 A 55-year-old male patient with history of hypertension was admitted to our hospital for an episode of atrial fibrillation (AF). TEE was performed and showed normal LA volume, absence of thrombi and spontaneous echo contrast in the LA, but, despite acquiring three-dimensional (3D) en-face views, we were unable to identify LAA. Congenital absence of LAA was suspected and multidetector cardiac CT confirmed the abnormality.
 
 
 
 Congenital absence of LAA is an extremely rare condition: only eighteen cases were described on a review of the literature published in 2020. Associations with other congenital abnormalities or with atrial fibrillation have been reported, but a causal relationship cannot be established. Multiple imaging modalities can be used to define the anatomy and function of LAA, to detect or rule out in situ thrombosis and to guide catheter-based therapies, but the most widely used technique is TEE. Among intracardiac thrombi in patients with non-valvular atrial fibrillation, more than 90% are identified in the LAA, meaning that the remaining 10% may develop in other sites of the LA. The congenital absence of LAA could be considered similar to LAA percutaneous occlusion or surgical exclusion; because of the few published randomized controlled trials, the current ESC guidelines on atrial fibrillation are unclear about the true thrombotic risk in these cases. Since LAA percutaneous occlusion is actually indicated only in cases of contraindications for long-term anticoagulant treatment, in our opinion in patients with non-valvular AF, LAA congenital absence, high stroke risk and low bleeding risk, anticoagulant therapy should be considered.
 
 
 
 Congenital absence of LAA is an extremely rare condition and its pathophysiological role, especially with regard to antithrombotic therapy in patients with AF, is still not well defined.


G. Bardelli

Papers

No evidence of association between prothrombotic gene Polymorphisms and the development of acute myocardial infarction at a young age

235 comparison of the prognostic relevance of different echocardiographic parameters of right ventricular systolic function in chronic heart failure

701 left atrial appendage congenital absence and atrial fibrillation