Preoperative versus postoperative survival in patients with univentricular heart: a nationwide, retrospective study of patients born in 1990-2015.

OBJECTIVES: Few data exist on mortality among patients with univentricular heart (UVH) before surgery. Our aim was to explore the results of intention to perform surgery by estimating preoperative vs postoperative survival in different UVH subgroups. DESIGN: Retrospective. SETTING: Tertiary centre for congenital cardiology and congenital heart surgery. PARTICIPANTS: All 595 Norwegian children with UVH born alive from 1990 to 2015, followed until 31 December 2020. RESULTS: One quarter (151/595; 25.4%) were not operated. Among these, only two survived, and 125/149 (83.9%) died within 1 month. Reasons for not operating were that surgery was not feasible in 31.1%, preoperative complications in 25.2%, general health issues in 23.2% and parental decision in 20.5%. In total, 327/595 (55.0%) died; 283/327 (86.5%) already died during the first 2 years of life. Preoperative survival varied widely among the UVH subgroups, ranging from 40/65 (61.5%) among patients with unbalanced atrioventricular septal defect to 39/42 (92.9%) among patients with double inlet left ventricle. Postoperative survival followed a similar pattern. Postoperative survival among patients with hypoplastic left heart syndrome (HLHS) improved significantly (5-year survival, 42.5% vs 75.3% among patients born in 1990-2002 vs 2003-2015; p<0.0001), but not among non-HLHS patients (65.7% vs 72.6%; p=0.22)-among whom several subgroups had a poor prognosis similar to HLHS. A total of 291/595 patients (48.9%) had Fontan surgery CONCLUSIONS: Surgery was refrained in one quarter of the patients, among whom almost all died shortly after birth. Long-term prognosis was largely determined during the first 2 years. There was a strong concordance between preoperative and postoperative survival. HLHS survival was improved, but non-HLHS survival did not change significantly. This study demonstrates the complications and outcomes encountering newborns with UVH at all major stages of preoperative and operative treatment.

Cause-Specific Mortality in Patients During Long-Term Follow-Up After Atrial Switch for Transposition of the Great Arteries.

Background Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short- (<10 years), mid- (10-20 years), and long-term (>20 years) follow-up after the operation. Methods and Results This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow-up of 33.6 years. The estimated risk of all-cause mortality reached 36.0% after 43 years of follow-up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short-, mid-, and long-term follow-up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively. Conclusions Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all-cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.

Mechanical Effects on Right Ventricular Function From Left Bundle Branch Block and Cardiac Resynchronization Therapy.

OBJECTIVES: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction. BACKGROUND: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function. METHODS: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers. RESULTS: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure. CONCLUSIONS: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185).

Afterload Hypersensitivity in Patients With Left Bundle Branch Block.

OBJECTIVES: This study sought to investigate the hypothesis that patients with left bundle branch block (LBBB) are hypersensitive to elevated afterload. BACKGROUND: Epidemiological data suggest that LBBB can provoke heart failure in patients with hypertension. METHODS: In 11 asymptomatic patients with isolated LBBB and 11 age-matched control subjects, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured by echocardiography. Systolic arterial pressure was increased by combining pneumatic extremity constrictors and handgrip exercise. To obtain more insight into mechanisms of afterload response, 8 anesthetized dogs with left ventricular (LV) micromanometer and dimension crystals were studied during acutely induced LBBB and aortic constriction. Regional myocardial work was assessed by LV pressure-dimension analysis. RESULTS: Consistent with normal afterload dependency, elevation of systolic arterial pressure by 38 ± 12 mm Hg moderately reduced LVEF from 60 ± 4% to 54 ± 6% (p < 0.01) in control subjects. In LBBB patients, however, a similar blood pressure increase caused substantially larger reduction in LVEF (p < 0.01), from 56 ± 6% to 42 ± 7% (p < 0.01). There were similar findings for GLS. In the dog model, aortic constriction abolished septal shortening (p < 0.02), and septal work decreased to negative values (p < 0.01). Therefore, during elevated systolic pressure, the septum made no contribution to global LV work, as indicated by net negative work, and instead absorbed energy from work done by the LV lateral wall. CONCLUSIONS: Moderate elevation of arterial pressure caused marked reductions in LVEF and GLS in patients with LBBB. This reflects a cardiodepressive effect of elevated afterload in the dyssynchronous ventricle and was attributed to loss of septal function.

Adding Speckle-Tracking Echocardiography to Visual Assessment of Systolic Wall Motion Abnormalities Improves the Detection of Myocardial Infarction.

BACKGROUND: The aim of this study was to investigate whether speckle-tracking echocardiography (STE) improves the detection of myocardial infarction (MI) over visual assessment of systolic wall motion abnormalities (SWMAs) using delayed enhancement cardiac magnetic resonance imaging as a reference. METHODS: Transthoracic echocardiography was performed in 95 patients with first ST segment elevation MI 110 days (interquartile range, 97-171 days) after MI and in 48 healthy control subjects. Two experienced observers independently assessed SWMAs. Separately, longitudinal peak negative, peak systolic, end-systolic, global strain, and strain rate were measured and averaged for the American Heart Association-recommended coronary artery perfusion territories. Receiver operating characteristic analysis was used to determine a single optimal cutoff value for each strain parameter. The diagnostic accuracy of an algorithm combining visual assessment and STE was evaluated. RESULTS: Median infarct size and transmurality were 15% (interquartile range, 7%-24%) and 64% (interquartile range, 46%-78%), respectively. Sensitivity, specificity, and accuracy of visual assessment to detect MI were 74% (95% CI, 63%-82%), 85% (95% CI, 72%-93%), and 78% (95% CI, 70%-84%), respectively. Among the strain parameters, SR had the highest diagnostic accuracy (area under the curve, 0.88; 95% CI, 0.83-0.94; cutoff value, -0.97 sec-1). The combination with STE improved sensitivity compared with visual assessment alone (94%; 95% CI, 86%-97%; P < .001), minimally affecting specificity (79%; 95% CI, 65%-89%; P = .607). Overall accuracy improved to 89% (95% CI, 82%-93%; P = .011). Multivariate analysis accounting for age and sex demonstrated that SR was independently associated with MI (odds ratio, 2.0; 95% CI, 1.6-2.7). CONCLUSIONS: The sensitivity and diagnostic accuracy of visually detecting chronic MI by assessing SWMAs are moderate but substantially improve when adding STE.

Survival in patients with univentricular hearts: the impact of right versus left ventricular morphology.

Objective: Patients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV). Methods: All 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX. Results: Among the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6). Conclusion: SRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS.

Diabetes mellitus and insulin resistance associate with left ventricular shape and torsion by cardiovascular magnetic resonance imaging in asymptomatic individuals from the multi-ethnic study of atherosclerosis.

BACKGROUND: Although diabetes mellitus (DM) and insulin resistance associate with adverse cardiac events, the associations of left ventricular (LV) remodeling and function with compromised glucose metabolism have not been fully evaluated in a general population. We used cardiovascular magnetic resonance (CMR) to evaluate how CMR indices are associated with DM or insulin resistance among participants before developing cardiac events. METHODS: We studied 1476 participants who were free of clinical cardiovascular disease and who underwent tagged CMR in the Multi-Ethnic Study of Atherosclerosis (MESA). LV shape and longitudinal myocardial shortening and torsion were assessed by CMR. A higher sphericity index represents a more spherical LV shape. Multivariable linear regression was used to evaluate the associations of DM or homeostasis model assessment-estimated insulin resistance (HOMA-IR) with CMR indices. RESULTS: In multiple linear regression, longitudinal shortening was lower in impaired fasting glucose than normal fasting glucose (NFG) (0.36% lower vs. NFG, p < 0.05); torsion was greater in treated DM (0.24 °/cm greater vs. NFG, p < 0.05) after full adjustments. Among participants without DM, greater log-HOMA-IR was correlated with greater LV mass (3.92 g/index, p < 0.05) and LV mass-to-volume ratio (0.05 /index, p < 0.01), and lower sphericity index (- 1.26/index, p < 0.01). Greater log-HOMA IR was associated with lower longitudinal shortening (- 0.26%/index, p < 0.05) and circumferential shortening (- 0.30%/index, p < 0.05). Torsion was positively correlated with log-HOMA-IR until 1.5 of log-HOMA-IR (0.16 °/cm/index, p = 0.030).), and tended to fall once above 1.5 of log-HOMA-IR (- 0.50 °/cm/index, p = 0.203). The sphericity index was associated negatively with LV mass-to-volume ratio (- 0.02/%, p < 0.001) and torsion (- 0.03°/cm/%, p < 0.001). CONCLUSIONS: Glucose metabolism disorders are associated with LV concentric remodeling, less spherical shape, and reduced systolic myocardial shortening in the general population. Although torsion is higher in participants who are treated for DM and impaired insulin resistance, myocardial shortening was progressively decreased with higher HOMA-IR and torsion was increased only with less severe insulin resistance. CLINICAL TRIAL REGISTRATION: Multi-Ethnic Study of Atherosclerosis (MESA): A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/ . Study Start Date: January 1999 ( NCT00005487 ).

Reference Ranges and Regional Patterns of Left Ventricular Strain and Strain Rate Using Two-Dimensional Speckle-Tracking Echocardiography in a Healthy Middle-Aged Black and White Population: The CARDIA Study.

BACKGROUND: Strain and strain rate are sensitive markers of left ventricular (LV) myocardial function. The aim of this study was to assess reference ranges and regional patterns of LV strain and strain rate using two-dimensional speckle-tracking echocardiography in a large population of black and white subjects. METHODS: This study involved a retrospective review of prospectively collected images in 557 participants in the Coronary Artery Risk Development in Young Adults study who remained healthy at the year 25 examination. LV deformation parameters were measured in apical four-chamber, apical two-chamber, and parasternal short-axis views in 509, 391, and 521 subjects, respectively. RESULTS: Patients' mean age was 49.6 ± 3.6 years, 61.6% were women, and 69.5% were white. White women showed the highest LV systolic and diastolic deformation values, reflected by a more negative reference range for apical four-chamber longitudinal strain (-16.4%; 95% prediction interval [PI], -20.8% to -12.0%) and a higher positive reference range for early diastolic strain rate (0.93 1/sec; 95% PI, 0.41 to 1.46 1/sec), respectively. The lowest LV systolic and diastolic deformation values were found in black men, with apical four-chamber longitudinal strain (14.7%; 95% PI, -19.1% to -10.3%) and early diastolic strain rate (0.79 1/sec; 95% PI, 0.42 to 1.16 1/sec). Absolute strain increased from the epicardium toward the endocardium. A base-to-apex gradient of longitudinal strain toward the apex was exhibited in inferior and inferoseptal regions and, in contrast, in the opposite direction in anterior and anterolateral walls. Sex had the strongest influence on LV deformation variability. CONCLUSIONS: Strain and strain rate reference values were sex and race related. White women showed the highest reference ranges for LV deformation, while the lowest values were found in black men. Significant layer- and level-specific patterns in regional LV deformation were identified.

Comparison of Electrocardiography Markers and Speckle Tracking Echocardiography for Assessment of Left Ventricular Myocardial Scar Burden in Patients With Previous Myocardial Infarction.

Myocardial scar burden is an important prognostic factor after myocardial infarction. This cohort study compared assessment of left ventricle scar burden between pathological Q waves on electrocardiography (ECG), Selvester multiparametric ECG scoring system for scar burden, and global longitudinal strain (GLS) by speckle-tracking echocardiography 6 months after myocardial infarction. The scar burden was defined by late gadolinium enhancement cardiac magnetic resonance as fraction of total left ventricle tissue. ECG measures were presence of pathologic Q waves and Selvester scores. GLS was the average of peak strain from 16 left ventricle segments. In 34 patients aged 58 ± 10 years (mean ± SD), the scar burden was 19% (9, 26) (median [quartiles]) and 79% had scar burden >5%. Patients with scar burden >5% more frequently had pathologic Q waves (63% vs 14%) and had worse Selvester scores (5 [3, 7] vs 0 [0, 1]) and worse GLS (-16.6 ± 2.4% vs -19.9 ± 1.1%). Pathologic Q waves, Selvester scores, ejection fraction, and GLS related to scar burden in univariable analyses. Sensitivity and specificity for detecting scar burden >5% was 63% and 86% (pathologic Q waves), 89% and 86% (Selvester score), 81% and 86% (ejection fraction), 89% and 86% (GLS), and 96% and 71% (combination of Q waves, Selvester score, and GLS). In conclusion, Selvester score and GLS related to scars 6 months after myocardial infarction, and pathologic Q waves were only weakly associated with scar and GLS was associated with scar independently of ECG markers.

Association of Aortic Stiffness With Left Ventricular Remodeling and Reduced Left Ventricular Function Measured by Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: This study sought to assess cross-sectional associations of aortic stiffness assessed by magnetic resonance imaging with left ventricular (LV) remodeling and myocardial deformation in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Aortic arch pulse wave velocity (PWV) was measured with phase contrast cine magnetic resonance imaging. LV circumferential strain (Ecc), torsion, and early diastolic strain rate were determined by tagged magnetic resonance imaging. Multivariable linear regression models were used to adjust for demographics and cardiovascular risk factors. Of 2093 participants, multivariable linear regression models demonstrated that higher arch PWV was associated with higher LV mass index (B=0.53 per 1 SD increase for log-transformed PWV, P<0.05) and LV mass to volume ratio (B=0.015, P<0.01), impaired LV ejection fraction (LVEF; B=-0.84; P<0.001), Ecc (B=0.55; P<0.001), torsion (B=-0.11; P<0.001), and early diastolic strain rate (B=-0.003; P<0.05). In sex stratified analysis, higher arch PWV was associated with higher MVR (B=0.02; P<0.05), impaired Ecc (B=0.60; P<0.001), and LVEF (B=-0.45; P<0.05), but with maintained torsion in women. Higher PWV was associated with impaired Ecc (B=0.49; P<0.001) and LVEF (B=-1.21; P<0.001), with lower torsion (B=-0.17; P<0.001) in men. CONCLUSIONS: Higher arch PWV is associated with LV remodeling, and reduced LV systolic and diastolic function in a large multiethnic population. Greater aortic arch stiffness is associated with concentric LV remodeling and relatively preserved LVEF with maintained torsion in women, whereas greater aortic arch stiffness is associated with greater LV dysfunction demonstrated as impaired Ecc, torsion, and LVEF, with less concentric LV remodeling in men.

Reduced long axis strain is associated with heart failure and cardiovascular events in the multi-ethnic study of Atherosclerosis.

PURPOSE: To propose long axis strain (LAS), a novel index of global left ventricle (LV) function, as a sensitive and powerful predictor of hard cardiovascular events and heart failure in the Multi-Ethnic Study of Atherosclerosis (MESA). MATERIALS AND METHODS: Strain is an index of relative myocardial deformation, and enables normalization for differences in heart size. Measurement of strain conventionally requires dedicated software and protocols for image acquisition. LAS, however, can be analyzed using a caliper tool from conventional LV long axis magnetic resonance imaging (MRI) cine loops, reflecting the average myocardial contraction in the longitudinal direction. In all, 1651 participants (53% men) of the MESA study, without a history of myocardial infarction or heart failure, were assessed using conventional cine MR images. LV lengths were assessed at end-diastole (EDL ) and end-systole (ESL ), and LAS was calculated as 100*(EDL -ESL )/EDL . Participants were followed for 6.8 ± 1.8 years for a composite endpoint of congestive heart failure or hard cardiovascular events, and the predictive ability of LAS was tested, unadjusted and adjusted for established cardiovascular risk factors. RESULTS: A total of 114 events were observed. Mean LAS was 11.7 ± 2.5% and 10.0 ± 2.7% in participants without and with events, respectively (P < 0.001). Increased LAS reduced the hazard ratio to 0.75 for univariate, and 0.88 for multivariate assessments, respectively (both P < 0.001). CONCLUSION: Assessment of long axis LV deformation by LAS is feasible and reproducible. Moreover, LAS predicts hard cardiovascular events and congestive heart failure in a multi-ethnic population without overt cardiovascular disease at inclusion. J. Magn. Reson. Imaging 2016;44:178-185.

Factors determining the magnitude of the pre-ejection leftward septal motion in left bundle branch block.

AIMS: An abnormal large leftward septal motion prior to ejection is frequently observed in left bundle branch block (LBBB) patients. This motion has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate factors that influence its magnitude. METHODS AND RESULTS: Left (LVP) and right ventricular (RVP) pressures and left ventricular (LV) volume were measured in eight canines. After induction of LBBB, LVP and, hence, the transmural septal pressure (PLV-RV = LVP-RVP) increased more slowly (P < 0.01) during the phase when septum moved leftwards. A biventricular finite-element LBBB simulation model confirmed that the magnitude of septal leftward motion depended on reduced rise of PLV-RV. The model showed that leftward septal motion was decreased with shorter activation delay, reduced global or right ventricular (RV) contractility, septal infarction, or when the septum was already displaced into the LV at end diastole by RV volume overload. Both experiments and simulations showed that pre-ejection septal hypercontraction occurs, in part, because the septum performs more of the work pushing blood towards the mitral valve leaflets to close them as the normal lateral wall contribution to this push is lost. CONCLUSIONS: Left bundle branch block lowers afterload against pre-ejection septal contraction, expressed as slowed rise of PLV-RV, which is a main cause and determinant of the magnitude of leftward septal motion. The motion may be small or absent due to septal infarct, impaired global or RV contractility or RV volume overload, which should be kept in mind if this motion is to be used in evaluation of CRT response.

Cumulative Blood Pressure in Early Adulthood and Cardiac Dysfunction in Middle Age: The CARDIA Study.

BACKGROUND: Cumulative blood pressure (BP) exposure may adversely influence myocardial function, predisposing individuals to heart failure later in life. OBJECTIVES: This study sought to investigate how cumulative exposure to higher BP influences left ventricular (LV) function during young to middle adulthood. METHODS: The CARDIA (Coronary Artery Risk Development in Young Adults) study prospectively enrolled 5,115 healthy African Americans and whites in 1985 and 1986 (baseline). At the year 25 examination, LV function was measured by 2-dimensional echocardiography; cardiac deformation was assessed in detail by speckle-tracking echocardiography. We used cumulative exposure of BP through baseline and up to the year 25 examination (millimeters of mercury × year) to represent long-term exposure to BP levels. Linear regression and logistic regression were used to quantify the association of BP measured repeatedly through early adulthood (18 to 30 years of age) up to middle age (43 to 55 years). RESULTS: Among 2,479 participants, cumulative BP measures were not related to LV ejection fraction; however, high cumulative exposure to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were associated with lower longitudinal strain rate (both p < 0.001). For diastolic function, higher cumulative exposures to SBP and DBP were associated with low early diastolic longitudinal peak strain rate. Of note, higher DBP (per SD increment) had a stronger association with diastolic dysfunction compared with SBP. CONCLUSIONS: Higher cumulative exposure to BP over 25 years from young adulthood to middle age is associated with incipient LV systolic and diastolic dysfunction in middle age.

Determinants of Aortic Root Dilatation and Reference Values Among Young Adults Over a 20-Year Period: Coronary Artery Risk Development in Young Adults Study.

Aortic size increases with age, but factors related to such dilatation in healthy young adult population have not been studied. We aim to evaluate changes in aortic dimensions and its principal correlates among young adults over a 20-year time period. Reference values for aortic dimensions in young adults by echocardiography are also provided. Healthy Coronary Artery Risk Development in Young Adults (CARDIA) study participants aged 23 to 35 years in 1990-1991 (n=3051) were included after excluding 18 individuals with significant valvular dysfunction. Aortic root diameter (ARD) by M-mode echocardiography at year-5 (43.7% men; age, 30.2 ± 3.6 years) and year-25 CARDIA exams was obtained. Univariable and multivariable analyses were performed to assess associations of ARD with clinical data at years-5 and -25. ARD from year-5 was used to establish reference values of ARD in healthy young adults. ARD at year-25 was greater in men (33.3 ± 3.7 versus 28.7 ± 3.4 mm; P<0.001) and in whites (30.9 ± 4.3 versus 30.5 ± 4.1 mm; P=0.006). On multivariable analysis, ARD at year-25 was positively correlated with male sex, white ethnicity, age, height, weight, 20-year gain in weight, active smoking at baseline, and 20-year increase in diastolic, systolic, and mean arterial pressure. A figure showing the estimated 95th percentile of ARD by age and body surface area stratified by race and sex is provided. This study demonstrates that smoking, blood pressure, and increase in body weight are the main modifiable correlates of aortic root dilation during young adulthood. Our study also provides reference values for ARD in young adults.

Cardiac responses to left ventricular pacing in hearts with normal electrical conduction: beneficial effect of improved filling is counteracted by dyssynchrony.

Cardiac resynchronization therapy (CRT) has been proposed in heart failure patients with narrow QRS, but the mechanism of a potential beneficial effect is unknown. The present study investigated the hypothesis that left ventricular (LV) pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start filling before the right ventricle (RV) during narrow QRS in an experimental model. LV and biventricular pacing were studied in six anesthetized dogs before and after the induction of LV failure. Function was evaluated by pressures and dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In the nonfailing heart, LV pacing gave the LV a head start in filling relative to the RV (P < 0.05) and increased LVEDV (P < 0.05). The response was similar during LV failure when RV diastolic pressure was elevated. The pacing-induced increase in LVEDV was attributed to a rightward shift of the septum (P < 0.01) due to an increased left-to-right transseptal pressure gradient (P < 0.05). LV pacing, however, also induced dyssynchrony (P < 0.05) and therefore reduced LV stroke work (P < 0.05) during baseline, and similar results were seen in failing hearts. Biventricular pacing did not change LVEDV, but systolic function was impaired. This effect was less marked than with LV pacing. In conclusion, pacing of the LV lateral wall increased LVEDV by displacing the septum rightward, suggesting a mechanism for a favorable effect of CRT in narrow QRS. The pacing, however, induced dyssynchrony and therefore reduced LV systolic function. These observations suggest that detrimental effects should be considered when applying CRT in patients with narrow QRS.

Association of CMR-measured LA function with heart failure development: results from the MESA study.

OBJECTIVES: The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals. BACKGROUND: Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population. METHODS: In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 ± 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 ± 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases. RESULTS: Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVImin) than control subjects (40 ± 13 mm(3)/m(2) vs. 33 ± 10 mm(3)/m(2) [p <0.001] for maximal LA index and 25 ± 11 mm(3)/m(2) vs. 17 ± 7 mm(3)/m(2) [p <0.001] for LAVImin). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 ± 11% vs. 38 ± 16%; p <0.001) and lower LA emptying fraction (40 ± 11% vs. 48 ± 9%; p <0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro-B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVImin (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF. CONCLUSIONS: Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVImin, measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals.

Framingham score and LV mass predict events in young adults: CARDIA study.

BACKGROUND: Framingham risk score (FRS) underestimates risk in young adults. Left ventricular mass (LVM) relates to cardiovascular disease (CVD), with unclear value in youth. In a young biracial cohort, we investigate how FRS predicts CVD over 20 years and the incremental value of LVM. We also explore the predictive ability of different cut-points for hypertrophy. METHODS: We assessed FRS and echocardiography-derived LVM (indexed by body surface area or height2.7) from 3980 African-American and white Coronary Artery Risk Development in Young Adults (CARDIA) participants (1990-1991); and followed over 20 years for a combined endpoint: cardiovascular death; nonfatal myocardial infarction, heart failure, cerebrovascular disease, and peripheral artery disease. We assessed the predictive ability of FRS for CVD and also calibration, discrimination, and net reclassification improvement for adding LVM to FRS. RESULTS: Mean age was 30±4 years, 46% males, and 52% white. Event incidence (n=118) across FRS groups was, respectively, 1.3%, 5.4%, and 23.1% (p<0.001); and was 1.4%, 1.3%, 3.7%, and 5.4% (p<0.001) across quartiles of LVM (cut-points 117 g, 144 g, and 176 g). LVM predicted CVD independently of FRS, with the best performance in normal weight participants. Adding LVM to FRS modestly increased discrimination and had a statistically significant reclassification. The 85th percentile (≥116 g/m2 for men; ≥96 g/m2 for women) showed event prediction more robust than currently recommended cut-points for hypertrophy. CONCLUSION: In a biracial cohort of young adults, FRS and LVM are helpful independent predictors of CVD. LVM can modestly improve discrimination and reclassify participants beyond FRS. Currently recommended cut-points for hypertrophy may be too high for young adults.

Long axis strain by MRI and echocardiography in a postmyocardial infarct population.

PURPOSE: To compare long axis strain (LAS) by magnetic resonance imaging (MRI) and echocardiography in a postinfarct patient population. Long axis left ventricle (LV) function is a sensitive index of incipient heart failure by echocardiography, but is less well established in MRI. LAS is an index of global LV function, which is easily assessed in cine loops provided by most cardiac MRI protocols. MATERIALS AND METHODS: In all, 116 patients (57 ± 9 years) were studied the same day using echocardiography and MRI 7.4 ± 4.1 months after a first myocardial infarction. LV length was measured in end diastole and end systole in conventional cine images with a temporal resolution of 50 msec or less, and LAS (%) was calculated as the change in LV length, relative to end diastole. Infarct mass was assessed by contrast-enhanced MRI. RESULTS: LAS was progressively reduced in patients with larger infarcts, and demonstrated good correlations with infarct mass (r = 0.55, P < 0.01). There was a good agreement between LAS assessed by echocardiography and MRI (r = 0.77, P < 0.01), and between LAS by MRI and speckle tracking strain by echocardiography (r = 0.74, P < 0.01). CONCLUSION: LAS is an index that allows measurement of LV long axis function by conventional cine MRI.

In juvenile dermatomyositis, cardiac systolic dysfunction is present after long-term follow-up and is predicted by sustained early skin activity.

OBJECTIVE: To compare systolic cardiac function in patients with juvenile dermatomyositis (JDM) with matched controls and examine associations between systolic and diastolic cardiac function and disease variables. METHODS: Fifty-nine patients, examined at follow-up, median 16.8 years (2-38 years) after disease onset, were compared with 59 age-matched and sex-matched controls. Echocardiography was performed and analysed blinded to patient information. We used mitral annulus displacement to assess the relative long-axis shortening of the left ventricle (long-axis strain) and early diastolic tissue velocity (e'), as markers for systolic and diastolic function, respectively. Disease activity and organ damage were assessed at follow-up by clinical examination and retrospectively by chart review. RESULTS: Long-axis strain was reduced in patients compared with controls (16.6% (2.5) vs 17.7% (2.0), mean (SD), p=0.001), whereas no difference was seen between patients with active and inactive disease. Disease duration correlated with systolic and diastolic function (rsp=-0.50 and rsp=-0.73, both p<0.001) and so did Myositis Damage Index (MDI) 1 year (rsp=-0.36 and rsp=-0.46) and MDI at follow-up (rsp=-0.33 and rsp=-0.60), all p<0.01. High early disease activity score (DAS) in skin (DAS skin 1 year), but not in muscle, predicted systolic (standardised ß=-0.28, p=0.011, R(2)=48%) and diastolic dysfunction (ß=-0.36, p<0.001, R(2)=72%) at follow-up. CONCLUSIONS: Long-axis strain was reduced in JDM patients compared with controls, suggesting systolic dysfunction. Impaired systolic and diastolic function was predicted by DAS skin 1 year. This indicates a common pathway to two different cardiac manifestations in JDM, perhaps with similar pathogenesis as skin affection.

Left ventricular mass and hypertrophy by echocardiography and cardiac magnetic resonance: the multi-ethnic study of atherosclerosis.

BACKGROUND: Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk. METHODS: Multi-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7) , height(2.7) , or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities. RESULTS: Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76. CONCLUSIONS: Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.