Multi-Ethnic Study of Atherosclerosis (MESA): JACC Focus Seminar 5/8

The MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute–sponsored prospective study aimed at studying the prevalence, progression, determinants, and prognostic significance of subclinical cardiovascular disease in a sex-balanced, multiethnic, community-dwelling U.S. cohort. MESA helped usher in an era of noninvasive evaluation of subclinical atherosclerosis presence, burden, and progression for the evaluation of atherosclerotic cardiovascular disease risk, beyond what could be predicted by traditional risk factors alone. Concepts developed in MESA have informed international patient care guidelines, providing new tools to effectively guide public health policy, population screening, and clinical decision-making. MESA is grounded in an open science model that continues to be a beacon for collaborative science. In this review, we detail the original goals of MESA, and describe how the scope of MESA has evolved over time. We highlight 10 significant MESA contributions to cardiovascular medicine, and chart the path forward for MESA in the year 2021 and beyond.     

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study

ObjectivesThis study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.BackgroundTo our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.MethodsProspective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.ResultsThe propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.ConclusionsAmong pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217)     

Outcomes in Patients With Hypertrophic Cardiomyopathy and Left Ventricular Systolic Dysfunction

BackgroundEnd-stage (ES) hypertrophic cardiomyopathy (HCM) has been considered a particularly grim and unfavorable disease complication, associated with substantial morbidity and mortality, frequently requiring heart transplant. Previous reports have included small numbers of patients with relatively short follow-up, predominantly in prior treatment eras.ObjectivesThe purpose of this study was to re-evaluate clinical profile and prognosis for end-stage heart failure in a large HCM cohort with contemporary management strategies.MethodsPatients at Tufts HCM Institute, from 2004 to 2017, were identified with ES and systolic dysfunction (ejection fraction [EF] <50%), followed for 5.8 ± 4.7 years (up to 18 years).ResultsOf the 2,447 patients, 118 (4.8%) had ES-HCM (EF 39 ± 9%; range 12% to 49%) at age 48 ± 15 years. Notably, over follow-up, 57 patients (48%) achieved clinical stability in New York Heart Association functional classes I/II with medical treatment (or cardiac resynchronization therapy), including 6 patients ≥10 years from ES diagnosis (up to 14 years). In total, 61 other patients (52%) developed refractory heart failure to disabling New York Heart Association functional classes III/IV (5.2%/year); 67% have survived, including 31 with heart transplant. Of the 118 ES patients, 21 had appropriate implantable cardioverter-defibrillator (ICD) therapy terminating potentially lethal tachyarrhythmias, with no difference in frequency of events in patients with EF 35% to 49% versus EF <35% (17% vs. 19%; p = 0.80). With all available treatment modalities, ES-related mortality was 1.9%/year, with 10-year survival of 85% (95% confidence interval: 77% to 94%). Mortality was 4-fold lower than previously reported for ES (8.0%/year), but exceeded 10-fold HCM with preserved EF (0.2%/year; p < 0.001).ConclusionsAlthough ES remains an important complication of HCM, contemporary treatment strategies, including ICDs and heart transplant, are associated with significantly lower mortality than previously considered. Primary prevention ICDs should be considered when EF is <50% in HCM. Rapid heart failure progression is not an inevitable consequence of ES, and some patients experience extended periods of clinical stability.     

Regional amyloid distribution and impact on mortality in light-chain amyloidosis: a T1 mapping cardiac magnetic resonance study

Background: T1 mapping allows quantitative assessment of “diffuse” deposition of amyloid protein in the myocardium. Early detection of cardiac involvement and potential prognostic improvement could benefit patients with AL amyloidosis.

Objectives: This study aims to evaluate the regional variation of amyloid infiltration in the left ventricle and the prognostic value of T1 mapping in patients with AL amyloidosis.

Methods: We prospectively enrolled 77 patients with AL amyloidosis who underwent cardiac magnetic resonance on a 3.0-T scanner. Native T1 and extracellular volume (ECV) were quantitated on the basal, mid, and apical levels of the left ventricle. Late gadolinium enhancement (LGE) pattern (no or non-specific LGE, sub-endocardial LGE, and transmural LGE) was also assessed. Forty healthy subjects served as controls. The primary end point was all-cause mortality.

Results: Basal ECV (26.9?±?2.8% versus 31.1?±?4.9%, p?<?.001) were lower than apical ECV in the healthy controls; however, basal ECV (60.6?±?11.5% versus 53.0?±?9.6%, p?=?.003) were significantly higher than apical ECV in patients with transmural LGE. During the follow-up period (median duration, 28?months; 25th–75th percentile, 13.5–38.0?months), 46 patients died. Basal ECV has the largest area under the curve of 0.845 (95% CI, 0.747–0.917) to predict all-cause mortality. Multivariable Cox analysis indicated that basal ECV was an independent prognostic factor and showed incremental prognostic value beyond NYHA class, Mayo stage, and LGE pattern.

Conclusion: We demonstrated that T1 mapping may have the potential to detect a characteristic amyloid deposition with a decreasing gradient from base to apex. Furthermore, myocardial ECV indicated that basal amyloid infiltration provided robust and incremental prognostic value in patients with AL amyloidosis.     

Utilization of oxygen by the contractile apparatus is disturbed during reperfusion of post-ischaemic myocardium

Post-ischaemic ventricular function remains depressed ( = myocardialstunning) despite nearly normal coronary blood flow during reperfusion.In order to illuminate the causes of this phenomenon, we studiedthe relationship between ventricular function and myocardialoxygen consumption (MVO_2tot) in experiments on 15 isolated rabbithearts perfused with erythrocyte suspension (hct=30%). Leftventricular systolic function was assessed by measuring aorticflow (ml. min ^–1), peak systolic pressure (L VP_max), dPldt_max,and early relaxation in terms of dPldt_min during control and30 min after the onset of reperfusion, following 20 min globalno-flow ischaemia. The pressure-volume area was calculated asa measure of total mechanical energy. The external mechanicalefficiency (E_ext) was assessed from stroke work and MVO_2torBothcontractile efficiency (E_con= inverse slope of the MVO₂-PVArelationship) and MVO₂ of the unloaded contracting heart (MVO_2unl=basal MVO₂ + MVO₂ for excitation-contraction coupling) werecalculated using pressure-volume area and MVO_2tot Results: At matched heart rate (149 ± 30 vs 147 ±31 min ^–1; mean ± SD) and end-diastolic volume(1.3 ± 0.2 ml), the systolic variables were significantlydecreased in the stunned myocardium: aortic flow: 38 ±13 vs9 ± 11 ml. min ^–1, LVP_max: 112 ±19vs 74±18mmHg, and dP/dt_max: 1475 ±400 vs 1075±275 mmHg. s^–1. Likewise, dP/dt_min was significantlyimpaired (– 1275 ±250 vs – 975 ±250).The decrease in pressure-volume area (570 ±280 vs 270±200mmHg.ml. 100g^–1) was not statistically significant. In contrast,both E_ext (0.75±0.29 vs 0.18±0.26 arbitrary units)and E_con (31 ± 18 vs 14± 7%) were significantlydecreased, whereas MVO_2tot (40±9 vs 34±8µl.beat^–1. 100g^–1) and MVO_2unl (26±9 vs22±6µl.beat^–1. 100g^–1) were not. Summary: Ventricular function after brief episodes of ischaemiais decreased whereas MVO_2tot is maintained, i.e. external efficiencyis decreased. MVO₂ for the unloaded contraction remained unchanged,indicating that MVO₂for excitation-contraction coupling is inappropriatelyhigh for the depressed contractile state. The decreased contractileefficiency indicates further that O₂ utilization of the contractileapparatus is disturbed during reperfusion.     

Diffuse Myocardial Fibrosis and Diastolic Function in Aortic Stenosis

ObjectivesThe aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS).BackgroundMyocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS.MethodsPatients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation.ResultsPatients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e′ <7 cm/s) and increased LV filling pressure (E/e′ ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e′ and higher E/septal e′ ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function.ConclusionsDiffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis.     

Registro Español de Marcapasos. XVI Informe Oficial de la Sección de Estimulación Cardiaca de la Sociedad Española de Cardiología (2018)

Introduction and objectivesThis report describes the result of the analysis of the implanted pacemakers reported to the Spanish Pacemaker Registry in 2018.MethodsThe analysis is based on the information provided by the European Pacemaker Identification Card and supplier-reported data on the overall number of implanted pacemakers.ResultsInformation was received from 90 hospitals, with a total of 12 148 cards, representing 31% of the estimated activity. Use of conventional and resynchronization pacemakers was 825 and 77 units per million people, respectively. The mean age of the patients receiving an implant was 78.3 years, and 54% of the devices were implanted in people aged > 80 years. A total of 77.1% were first implants and 21.6% corresponded to generator exchanges. Bicameral sequential pacing was the most frequent pacing mode but was less frequently used in patients aged > 80 years and in women. Single chamber VVI/R pacing was used in 28% of patients with sick sinus syndrome and in 24.7% of those with atrioventricular block, despite being in sinus rhythm.ConclusionsThe total consumption of pacemaker generators in Spain increased by 1.2% compared with 2017, mainly due to an 8.7% increase in cardiac resynchronization therapy with pacemaker generators. Selection of pacing mode was directly influenced by age and sex.     

Novel use of a modified Amplatzer Vascular Plug® to occlude a patent ductus arteriosus in two patients

We describe two cases in which a patent ductus arteriosus (PDA) was successfully occluded percutaneously, using the novel approach of prefilling an Amplatzer Vascular Plug® with embolization coils to decrease the risk of residual shunting through the device. One patient was a small premature neonate, and the other was a child with an aneurismal, tubular PDA with no aortic ampulla. These are situations in which more popular PDA devices such as the Amplatzer Duct Occluder® may be contraindicated. © 2008 Wiley‐Liss, Inc.