Integrating Measures of Myocardial Fibrosis in the Transition from Hypertensive Heart Disease to Heart Failure.

PURPOSE OF REVIEW: This review aims to summarize recent developments in identifying and quantifying both the presence and amount of myocardial fibrosis by imaging and biomarkers. Further, this review seeks to describe in general ways how this information may be used to identify hypertension and the transition to heart failure with preserved ejection fraction. RECENT FINDINGS: Recent studies using cardiac magnetic resonance imaging highlight the progressive nature of fibrosis from normal individuals to those with hypertension to those with clinical heart failure. However, separating hypertensive patients from those with heart failure remains challenging. Recent studies involving echocardiography show the subclinical myocardial strain changes between hypertensive heart disease and heart failure. Lastly, recent studies highlight the potential use of biomarkers to identify those with hypertension at the greatest risk of developing heart failure. In light of the heterogeneous nature between hypertension and heart failure with preserved ejection fraction, an integrated approach with cardiac imaging and biomarker analysis may enable clinicians and investigators to more accurately characterize, prevent, and treat heart failure in those with hypertension.

Early versus late percutaneous revascularization in patients hospitalized with non ST-segment elevation myocardial infarction: The atherosclerosis risk in communities surveillance study.

BACKGROUND: Current guidelines recommend early invasive intervention (<24 hr) for high risk patients with non-ST-segment elevation myocardial infarction (NSTEMI). A delayed invasive strategy (24-72 hr) is considered reasonable for low risk patients. The real-world effectiveness of this strategy is unknown. METHODS: The ARIC Study has conducted hospital surveillance of acute myocardial infarction (MI) since 1987. NSTEMI was classified using a validated algorithm. We limited our study to patients undergoing early (<24 hr of the event onset), or late (≥24 hr) percutaneous coronary intervention (PCI). Patients were stratified into low (TIMI score 2-4), and high risk (TIMI score 5-7, or presence of cardiogenic shock, ventricular fibrillation, or cardiac arrest). Associations between early versus late PCI and mortality were analyzed using multivariable logistic regression adjusted for demographics, hospitalization year, TIMI score, and comorbidities. RESULTS: From 1987 to 2012, 6,746 patients were hospitalized with NSTEMI and underwent PCI. Most were white (79%), male (68%), with mean age 61 years. The 28-day and 1-year mortality were 2% and 5%, respectively. Most revascularizations (65%) were late. After accounting for potential confounders, early PCI was associated with a 58% reduced 28-day mortality (OR = 0.42; 95% CI: 0.21-0.84) for the entire population, and 57% reduced mortality (OR = 0.43; 95% CI: 0.21-0.88) for high risk patients. By 1-year of follow up, there was no significant difference in mortality with respect to early vs. late PCI. CONCLUSION: In hospitalized NSTEMI patients with high risk of clinical events, early PCI is associated with improved 28-day survival.

Comparison of paravalvular aortic leak characteristics in the Medtronic CoreValve versus Edwards Sapien Valve: Paravalvular aortic leak characteristics.

OBJECTIVES: Temporally quantify and localize paravalvular aortic leak (PVL) after transcatheter aortic valve replacement (TAVR) in the Medtronic CoreValve (MCV) versus the Edwards Sapien Valve (ESV). BACKGROUND: In order to increase the precision of THV selection and PVL intervention, an understanding of PVL characteristics is essential. METHODS: The frequency, severity, and location of post-TAVR PVL were evaluated with transthoracic echocardiography pre-discharge, one month, and one-year post-procedure in 202 patients receiving a MCV (N = 120) or ESV (N = 81). This was done through application of a clock face to the short axis of the aortic valve in order to divide the area into three tertiles. RESULTS: Pre-discharge differences between PVL frequency and severity in the MCV and ESV lost significance over time. Localizing these trends, MCV PVL frequency and severity significantly decreased in the first and third tertiles during most time periods while PVL in the second tertile of the MCV or in any of the tertiles of the ESV failed to improve. Presence of pre-discharge PVL was predictive of 30-day HF readmission and/or death (OR = 3.16, 95% CI: 0.99-10.12). Presence of pre-discharge and 30-day PVL was predictive of 1-year HF readmissions and/or death (OR = 2.12, 95% CI: 1.09-4.13 and OR = 1.99, 95% CI: 0.96-4.12). CONCLUSIONS: When comparing the MCV and ESV, not all locations of PVL improve equally over time, which has implications for heart failure readmissions. This could be used to influence valve selection and to identify cases in which earlier intervention on PVL may be appropriate.

Asymptomatic myocardial ischemia forecasts adverse events in cardiovascular magnetic resonance dobutamine stress testing of high-risk middle-aged and elderly individuals.

BACKGROUND: Current guidelines for assessing the risk of experiencing a hospitalized cardiovascular (CV) event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged < 60 years, and do not address the possibility of unrecognized "silent myocardial ischemia" in middle aged and older adults. METHODS: We performed dobutamine cardiovascular magnetic resonance (CMR) stress testing in 327 consecutively recruited participants aged > 55 years without CV-related symptoms nor known coronary artery disease, but otherwise at increased risk for a future CV event due to pre-existing hypertension or diabetes mellitus for at least 5 years. After adjusting for the demographics and CV risk factors, log-rank test and Cox proportional hazards models determined the additional predictive value of the stress test results for forecasting hospitalized CV events/survival. Either stress-induced LV wall motion abnormalities or perfusion defects were used to indicate myocardial ischemia. RESULTS: Participants averaged 68 ± 8 years in age; 39% men, 75% Caucasian. There were 38 hospitalized CV events or deaths which occurred during a mean follow-up of 58 months. Using Kaplan-Meier analyses, myocardial ischemia identified future CV events/survival (p <  0.001), but this finding was more evident in men (p <  0.001) versus women (p = 0.27). The crude hazard ratio (HR) of myocardial ischemia for CV events/survival was 3.13 (95% CI: 1.64-5.93; p < 0.001). After accounting for baseline demographics, CV risk factors, and left ventricular ejection fraction/mass, myocardial ischemia continued to be associated with CV events/survival [HR: 4.07 (95% CI: 1.95-8.73) p < 0.001]. CONCLUSIONS: Among asymptomatic middle-aged individuals with risk factors for a sentinel CV event, the presence of myocardial ischemia during dobutamine CMR testing forecasted a future hospitalized CV event or death. Further studies are needed in middle aged and older individuals to more accurately characterize the prevalence, significance, and management of asymptomatic myocardial ischemia. TRIAL REGISTRATION: ( ClinicalTrials.gov identifier): NCT00542503 and was retrospectively registered on October 11th, 2007.

Evaluation and management of left ventricular noncompaction cardiomyopathy.

Left ventricular (LV) noncompaction cardiomyopathy (LVNC) is a form of cardiomyopathy in which trabeculations fail to "compact" with the left ventricular endocardium during fetal cardiac development and is classically associated with subsequent impairment of LV function, significant mortality, ventricular dysrhythmias, and embolic phenomena. As awareness and medical imaging quality have improved, it is becoming easier to identify trabeculations that traverse the LV cavity and serve as a distinguishing feature of this disorder. Differentiating true noncompaction from mild increases in trabeculations requires prudent imaging and clinical correlation. This review seeks to discuss the potential methods of evaluating left ventricular trabeculations, the role of increased trabeculations in cardiovascular disease, and how their presence may affect clinical management.

Clinical significance of intermediate left ventricular trabeculations in cardiac magnetic resonance.

OBJECTIVE: Although the clinical importance of left ventricular noncompaction cardiomyopathy (LVNC) is known, few data exist that describe the prognosis associated with intermediate levels of LV trabeculations that do not meet criteria for LVNC. METHODS: Trabeculation/possible LVNC by CMR was retrospectively observed among 122 consecutive cases. We assessed the end-systolic noncompacted-to-compacted ratios (ESNCCR) along with deaths, embolic events, congestive heart failure (CHF) readmissions, ventricular arrhythmias, myocardial thickening (MT), and ejection fraction (EF). ESNCCRs were categorized as follows: <1, 1<1.5, 1.5<2, ≥2. General linear models were used to compare combined events (death, CHF readmission, embolism, ventricular arrhythmia) between categories of ESNCCR. There were 3 models used: model 1: unadjusted; model 2: adjusted for age, race, gender, body surface area, LV ejection fraction, and trabeculated segments; model 3: model 2+adjustment for myocardial thickening. RESULTS: In model 1, those with an ESNCCR<1 had a lower association with composite clinical events than those with a ratio between 1.5<2 and those≥2 (P<0.002 and P<0.001, respectively). In model 2, the lower association continued, (P=0.009 and P<0.001, respectively), but in model 3, those with a ratio from 1.5-2 only had a trend towards a higher association with composite clinical events than those with a ratio<1 (P=-0.09). Those with a ratio≥2 continued to have a higher association (P=-0.001). CONCLUSION: Patients with intermediate trabeculations not meeting criteria for LVNC had a higher association with composite clinical events, but it was mediated by decreased myocardial thickening in the associated compacted layer.

Mitral regurgitation in left ventricular noncompaction cardiomyopathy assessed by cardiac MRI.

BACKGROUND AND AIM OF THE STUDY: Previous case reports have described patients with left ventricular noncompaction cardiomyopathy (LVNC) with significant mitral regurgitation (MR). The study aim was to determine if LVNC is associated with MR, as assessed by cardiac magnetic resonance imaging (cMRI). METHODS: LVNC, assessed with cMRI, was observed retrospectively among 122 consecutive cases, 31 of whom had an end-systolic noncompacted-to-compacted ratio (ESNCCR) ≥ 2. In addition, 40 normal subjects undergoing cMRI and 40 with moderate to severe MR were included as controls. Using cine images, the ESNCCR and left ventricular (LV) and right ventricular (RV) stroke volumes were measured. The mitral regurgitant fraction (MRF) was calculated by dividing the difference between the RV and LV stroke volumes by the LV stroke volume. The total papillary muscle (TPM) area was measured from the mid short-axis view. Adjusting for age, race, gender and body surface area, an analysis of covariance was conducted to determine whether MRF and TPM were associated with ESNCCR ≥ 2. Adjusted means were presented with 95% confidence intervals. RESULTS: After adjustment, the MRF in patients with ESNCCR ≥ 2 was higher than in controls, but did not differ from that in patients with significant MR (21 ± 6.5% versus 2.7 ± 12% versus 29.2 ± 11%, p = 0.039 and p = 0.3, respectively). Further, patients with ESNCCR ≥ 2 had a lower TPM than normal controls or those with moderate to severe MR (1.89 ± 0.28 cm2 versus 3.6 ± 0.26 cm2 versus 3.7 ± 0.24 cm2; p < 0.001 and p < 0.001, respectively). CONCLUSION: LVNC is associated with increased MR, as assessed using cMRI. LVNC is also associated with abnormalities in the papillary muscle anatomy, which may predispose to MR.

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults.

BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05). CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

Preventing new-onset heart failure: Intervening at stage A.

Heart failure (HF) prevention is an urgent public health need with national and global implications. Stage A HF patients do not show HF symptoms or structural heart disease but are at risk of HF development. There are no unique recommendations on detecting Stage A patients. Patients in Stage A are heterogeneous; many patients have different combinations of risk factors and, therefore, have markedly different absolute risks for HF. Comprehensive strategies to prevent HF at Stage A include intensive blood pressure lowering, adequate glycemic and lipid management, and heart-healthy behaviors (adopting Life's Essential 8). First and foremost, it is imperative to improve public awareness of HF risk factors and implement healthy lifestyle choices very early. In addition, recognize the HF risk-enhancing factors, which are nontraditional cardiovascular (CV) risk factors that identify individuals at high risk for HF (genetic susceptibility for HF, atrial fibrillation, chronic kidney disease, chronic liver disease, chronic inflammatory disease, sleep-disordered breathing, adverse pregnancy outcomes, radiation therapy, a history of cardiotoxic chemotherapy exposure, and COVID-19). Early use of biomarkers, imaging markers, and echocardiography (noninvasive measures of subclinical systolic and diastolic dysfunction) may enhance risk prediction among individuals without established CV disease and prevent chemotherapy-induced cardiomyopathy. Efforts are needed to address social determinants of HF risk for primordial HF prevention.Central illustrationPolicies developed by organizations such as the American Heart Association, American College of Cardiology, and the American Diabetes Association to reduce CV disease events must go beyond secondary prevention and encompass primordial and primary prevention.

Assessment of Prevalence, Clinical Characteristics, and Risk Factors Associated With "Low Flow State" Using Cardiac Magnetic Resonance.

Objective: To assess prevalence, clinical characteristics, and risk factors associated with low flow state (LFS) in a multiethnic population with normal left ventricular ejection fraction (LVEF). Patients and Methods: The study included 4398 asymptomatic participants undergoing cardiac magnetic resonance from July 17, 2000, to August 29, 2002. Left ventricular (LV) mass, volume, and myocardial contraction fraction were assessed. Low flow state was defined as stroke volume index (SVi of <35 mL/m2). Clinical characteristics, cardiac risk factors, and cardiac magnetic resonance findings were compared between LFS and normal flow state (NFS) groups (NFS: SVi of ≥35 mL/m2). Results: There were significant differences in the prevalence of LFS in different ethnic groups. Individuals with LFS were older (66±9.6 vs 61±10 years; P<.0001). The prevalence of LFS was 19% in the group aged older than 70 years. The logistic multivariable regression analysis found that age was independently associated with LFS. The LFS group had significantly higher prevalence of diabetes (30% vs 24%; P=.001), LV mass-volume ratio (1.13±0.22 vs 0.91±0.15; P<.0001), inflammatory markers, a lower LV mass index (59±10 vs 65±11 kg/m2; P<.001), lower myocardial contraction fraction (58.1±10.6% vs 75.7±13%; P<.001), and a lower left atrial size index (32.2±4.6 vs 36.7±5.9 mm/m2; P<.0001) than NFS. Conclusion: Low flow state may be considered an under-recognized clinical entity associated with increasing age, multiple risk factors, increased inflammatory markers, a lower LV mass index, and suboptimal myocardial performance despite the presence of normal LVEF and absence of valvular disease.

Quantifying Cardiothoracic Variation with Posture and Respiration to Inform Cardiac Device Design.

PURPOSE: With extravascular implantable cardioverter defibrillator leads placed beneath the sternum, it is important to quantify heart motion relative to the rib cage with postural changes and respiration. METHODS: MRI scans from five males and five females were collected in upright and supine postures at end inspiration [n = 10 each]. Left and right decubitus [n = 8 each] and prone [n = 5] MRIs at end inspiration and supine MRIs at end expiration [n = 5] were collected on a subset. Four cardiothoracic measurements, six cardiac measurements, and six cardiac landmarks were collected to measure changes across different postures and stages of respiration. RESULTS: The relative location of the LV apex to the nearest intercostal space was significantly different between the supine and decubitus postures (average ± SD difference: - 15.7 ± 11.4 mm; p < 0.05). The heart centroid to xipho-sternal junction distance was 9.7 ± 7.9 mm greater in the supine posture when compared to the upright posture (p < 0.05). Cardiac landmark motion in the lateral direction was largest due to postural movement (range 23-50 mm) from the left decubitus to the right decubitus posture, and less influenced by respiration (5-17 mm). Caudal-cranial displacement was generally larger due to upright posture (13-23 mm caudal) and inspiration (7-20 mm cranial). CONCLUSIONS: This study demonstrates that the location of the heart with respect to the rib cage varies with posture and respiration. The gravitational effects of postural shifts on the heart position are roughly 2-3 times larger than the effects of normal respiration.

Relation of glycemic status with unrecognized MI and the subsequent risk of mortality: The Jackson Heart Study.

Background: Almost 1/3 to 1/2 of initial myocardial infarctions (MI) may be silent or unrecognized (UMI), which forecasts future clinical events. Further, limited data exist to describe the potential risk for UMI in African-Americans. The relationship of glucose status with UMI was examined in the Jackson Heart Study: a cohort of African-American individuals. Methods and results: At baseline, there were 5,073 participants with an initial 12-lead electrocardiogram (ECG) and fasting glucose measured. Of these participants, 106(2.1%) had a UMI, and 268(4.2%) had a recognized MI. This population consisted of 3,233 (63.7%) participants with normal fasting glucose (NFG), 533 (10.5%) with IFG, and 1,039 (20.4%) with DM. Logistic regression investigated the relationship between glucose status and UMI. Cox proportional hazard models determined the significance of all-cause mortality during follow-up by MI status. The sample was 65% female with a mean age of 55.3 ± 12.9 years. Over a mean follow-up of 10.4 years, there were 795 deaths. Relative to NFG, the crude odds ratio (OR) estimates for UMI at baseline with IFG and DM were 1.00(95% CI:0.48-2.14) and 3.22(2.15-4.81), respectively. With adjustment, DM continued to be significantly associated with UMI [2.30 (1.42-3.71)]. Overall, participants with a baseline UMI had an adjusted Hazard ratio (HR) of 2.00(1.39-2.78) of death compared to no prior MI. Compared to those with no MI, those with a recognizedMI had an adjusted HR of 1.70(1.31-2.17) for mortality. Conclusions: DM is associated with UMI in African-Americans. Further, a UMI carried similar risk of death compared to those with a recognized MI.

The Simulated Cardiology Clinic: A Standardized Patient Exercise Supporting Medical Students' Biomedical Knowledge and Clinical Skills Integration.

Introduction: Development of cardiac disease-related diagnostic skills-including hypothesis-driven data gathering, heart sound interpretation, and ECG interpretation-is an important component of medical student training. Prior studies indicate trainees' performance of these skills is limited. Simulation provides students with opportunities to practice integrating their developing knowledge in a relevant clinical context. We developed a simulated clinic activity for second-year medical students consisting of standardized patient (SP) cases representing cardiovascular (CV) diseases. Methods: Student small groups rotated through four SP encounters. For each case, one student performed the history, after which the whole small group listened to audio files of heart sounds, interpreted an ECG, and collaboratively developed a prioritized differential diagnosis. The CV course director met with students for a large-group debrief, highlighting key learning points. We collected learners' evaluations of the event through an online survey. Results: Of students, 276 participated in this activity over the course of 2 years. Nearly all students assessed the activity as extremely or quite effective for applying learning content from the CV course (97%, 2018; 93%, 2019), and for practicing how to approach chest pain, shortness of breath, palpitations, and fatigue (100%, 2018; 95%, 2019). The most helpful aspects were reinforcement of CV disease illness scripts, hypothesis-driven data gathering practice, ECG interpretation, and applying knowledge and skills in a realistic context. Discussion: SP encounters representing CV conditions can effectively provide opportunities for students to integrate basic science knowledge and clinical skills. Students assessed the activity as helpful and engaging.

Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress.

BACKGROUND: Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women. METHODS: Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress. RESULTS: We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress. CONCLUSIONS: Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men.

Ten-year longitudinal change in aortic stiffness assessed by cardiac MRI in the second half of the human lifespan: the multi-ethnic study of atherosclerosis.

AIMS: Longitudinal determinants of aortic stiffness (AS) measured by magnetic resonance imaging (MRI) have not been assessed in a large community-based population. Our aim was to examine the determinants of change in thoracic AS over 10 years of follow-up in a multi-ethnic population of individuals 45 years of age and older measured by MRI. METHODS AND RESULTS: We studied 1160 participants (mean age = 60 ± 9 years at baseline, 45% male) with aortic MRI at both the MESA Year 0 and Year 10 examinations. Ascending and descending aorta distensibility (AAD/DAD) and aortic arch pulse-wave velocity (PWV) were measured using MRI. Determinants of the change in AS parameters over 10 years were assessed using linear regression adjusted for baseline values, demographic variables, baseline risk factors and change in risk factors, and chronic risk exposure. AAD and DAD decreased slightly (5% decrease in median for AAD: 1.33-1.26 mmHg(-1) · 10(-3), P = 0.008; 5% decrease in median for DAD: 1.73-1.64 mmHg(-1) · 10(-3), P < 0.001), and PWV increased over 10 years (18% increase in median: 6.8-8.0 m/s P < 0.001). Baseline age was related to a reduction in AAD and DAD and an increase in PWV throughout the follow-up period. Baseline and change in mean blood pressure and continued smoking were associated with a reduction in AAD and an increase in PWV. Furthermore, baseline heart rate was also related to a reduction in AAD and DAD. Blood pressure normalization was related to less aortic stiffening throughout the follow-up period. CONCLUSIONS: In our longitudinal, community-based cohort study of adult individuals aged 45 years or greater, greater mean blood pressure and a history of smoking history were associated with increased aortic stiffening over 10 years as assessed by MRI.

The Role of Cardiovascular Magnetic Resonance (CMR) and Computed Tomography (CCT) in Facilitating Heart Failure Management.

OPINION STATEMENT: Cardiovascular magnetic resonance (CMR) and cardiac computed tomography (CCT) offer advantages for detecting left or right ventricular dysfunction in patients with or suspected of heart failure. CMR does not expose patients to ionizing radiation, and thus is well-suited for functional assessments and serial studies. CCT provides high spatial resolution, making it useful for the identification of coronary arteriosclerosis associated with ischemic cardiomyopathy. In this review, the clinical applications of CMR and CCT are individually discussed, with comparisons made between them to examine the strengths of each modality. The major techniques for each modality are outlined, as well as their uses for the evaluation of cardiomyopathy in heart failure patients with reduced left ventricular ejection fraction, preserved left ventricular ejection fraction, and valvular heart disease. Finally, we review the utility of CMR and CCT in determining which patients will benefit from cardiac resynchronization therapy.

Comparison of systolic and diastolic criteria for isolated LV noncompaction in CMR.

OBJECTIVES: This study used cardiac magnetic resonance (CMR) to compare standard criteria for left ventricular noncompaction (LVNC). BACKGROUND: LVNC as a distinct cardiomyopathy is supported by a growing number of publications. Echocardiographic and CMR criteria have been established to diagnosis LVNC but have led to concerns of diagnostic accuracy. METHODS: Trabeculation/possible LVNC by CMR was retrospectively observed in 122 consecutive cases. We compared the standard end-systolic noncompacted-to-compacted ratio (ESNCCR), end-diastolic noncompacted:compacted ratio (EDNCCR), and trabecular mass-to-total mass ratio (TMTMR) along with deaths, embolic events, congestive heart failure (CHF) readmissions, ventricular arrhythmias, myocardial thickening (MT), left ventricular ejection fraction (LVEF), 3-dimensional sphericity index (3DSi), and left ventricular end-diastolic volume index. Adjusting for age, race, sex, body surface area, diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease, and CHF, logistic regression was used to compare combined events (death, CHF readmission, embolism, ventricular arrhythmia) between ESNCCR, EDNCCR, and TMTMR. Adjusting for same covariates except CHF, logistic regression was used to compare the odds of CHF for those who met criteria and those who did not. Using analysis of covariance, adjusted means for LVEF, MT, 3DSi, and left ventricular end-diastolic volume index were generated. RESULTS: ES criteria had a higher odds ratio (8.6; 95% confidence interval [CI]: 2.5 to 33) for combined events than ED criteria (1.8; 95% CI: 0.6 to 5.8) or TMTMR criteria (3.14; 95% CI: 1.09 to 10.2). The odds ratio of CHF for those who met ESNCCR criteria was 29.4 (95% CI: 6.6 to 125), but the odds ratio of CHF for those who met EDNCCR criteria was 3.3 (95% CI: 1.1 to 9.2). After adjustment, those who met criteria for noncompaction by ESNCCR had a lower LVEF and less MT than those who did not (p = 0.01 and p = 0.003, respectively), but there was no difference between those who met criteria for EDNCCR or the TMTMR criteria and those who did not. CONCLUSIONS: ES measures of LVNC have stronger associations with events, CHF, and systolic dysfunction than other measures.

Weekly doxorubicin increases coronary arteriolar wall and adventitial thickness.

BACKGROUND: Doxorubicin (DOX) is associated with premature cardiovascular events including myocardial infarction. This study was performed to determine if the weekly administration of DOX influenced coronary arteriolar medial and/or adventitial wall thickening. METHODS: Thirty-two male Sprague-Dawley rats aged 25.1± 2.4 weeks were randomly divided into three groups and received weekly intraperitoneal injections of normal saline (saline, n = 7), or low (1.5 mg/kg to 1.75 mg/kg, n = 14) or high (2.5 mg/kg, n = 11) doses of DOX. The animals were treated for 2-12 weeks, and euthanized at pre-specified intervals (2, 4, 7, or 10+ weeks) to obtain histopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thickness (medial thickness + adventitial thickness). RESULTS: Lumen diameter was similar across all groups (saline: 315±34 µm, low DOX: 286±24 µm, high DOX: 242±27 µm; p = 0.22). In comparison to animals receiving weekly saline, animals receiving weekly injections of 2.5 mg/kg of DOX experienced an increase in medial (23±2 µm vs. 13±3 µm; p = 0.005), and total wall thickness (51±4 µm vs. 36±5 µm; p = 0.022), respectively. These increases, as well as adventitial thickening became more prominent after normalizing for lumen diameter (p<0.05 to p<0.001) and after adjusting for age, weight, and total cumulative DOX dose (p = 0.02 to p = 0.01). Animals receiving low dose DOX trended toward increases in adventitial and total wall thickness after normalization to lumen diameter and accounting for age, weight, and total cumulative DOX dose (p = 0.06 and 0.09, respectively). CONCLUSION: In conclusion, these data demonstrate that weekly treatment of rats with higher doses of DOX increases coronary arteriolar medial, adventitial, and total wall thickness. Future studies are warranted to determine if DOX related coronary arteriolar effects are reversible or preventable, exacerbate the known cardiomyopathic effects of DOX, influence altered resting or stress-induced myocardial perfusion, or contribute to the occurrence of myocardial infarction.

Trabeculated (noncompacted) and compact myocardium in adults: the multi-ethnic study of atherosclerosis.

BACKGROUND: A high degree of noncompacted (trabeculated) myocardium in relationship to compact myocardium (trabeculated to compact myocardium [T/M] ratio >2.3) has been associated with a diagnosis of left ventricular noncompaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters. METHODS AND RESULTS: The thickness of trabeculation and the compact myocardium were measured in 8 left ventricular regions on long axis cardiac MR steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable, 140 (43%) had a T/M ratio >2.3 in at least 1 region; in 20 of 323 (6%), T/M >2.3 was present in >2 regions. A multivariable linear regression model revealed no association of age, sex, ethnicity, height, and weight with maximum T/M ratio in participants without cardiac disease or hypertension (P>0.05). In the entire cohort (n=1000), left ventricular ejection fraction (ß=-0.02/%; P=0.015), left ventricular end-diastolic volume (ß=0.01/mL; P<0.0001), and left ventricular end-systolic volume (ß=0.01/mL; P<0.001) were associated with maximum T/M ratio in adjusted models, whereas there was no association with hypertension or myocardial infarction (P>0.05). At the apical level, T/M ratios were significantly lower when obtained on short- compared with long-axis images (P=0.017). CONCLUSIONS: A ratio of T/M of >2.3 is common in a large population-based cohort. These results suggest re-evaluation of the current cardiac MR criteria for left ventricular noncompaction may be necessary.

Modification of the effect of glycemic status on aortic distensibility by age in the multi-ethnic study of atherosclerosis.

Elevated serum glucose from diabetes mellitus (DM) or impaired fasting glucose shares many mechanisms with aging that decrease aortic distensibility (AD), such as glycation of the extracellular matrix. However, few data compare the simultaneous effects of elevated serum glucose and aging on AD. To study this, we examined the relationship among fasting glucose status, age, and AD in the Multi-Ethnic Study of Atherosclerosis: a multiethnic cohort of individuals aged 45 to 84 years without clinical cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis, participants with normal fasting glucose (n=2270), impaired fasting glucose (n=870), and DM (n=412) underwent MRI assessment of proximal thoracic aortic distensibility. This sample was 46% male, 42% white, 30% black, 11% Asian, and 17% Hispanic. The relationship among glucose status, age, and AD was analyzed with general linear models by adjusting for factors influential on AD. An interaction term was used to determine whether age modified the effect of glucose status on AD. AD was lowest among those with DM. The interaction term was significant (P=0.024). Comparing participants <65 years of age, AD was different between normal fasting glucose and DM (P<0.01) and between normal fasting glucose and impaired fasting glucose (P=0.02). In those >65 years of age, the fasting glucose group was no longer a significant predictor of AD. Our data indicate that there are overall differences in AD among DM, impaired fasting glucose, and normal fasting glucose. However, age modified the effect of glucose status such that differences between the groups diminished with advancing age.