Gustavo J. Volpe

Evaluation of Cardiac Involvement During Dengue Viral Infection

BACKGROUND  Dengue is a disease whose clinical manifestations range from asymptomatic infections to a severe disease. There have been some previous reports of myocardial involvement in dengue, but this association has not been completely established. METHODS  From January to July of 2011, patients hospitalized with dengue, confirmed through dengue nonstructural protein 1 and/or immunoglobulin M detection, were included in this study and troponin I and N terminal fragment of B-type natriuretic peptide levels were determined. Patients with abnormal biomarkers underwent echocardiography and when any abnormality was detected, they underwent cardiac magnetic resonance imaging. RESULTS  Eighty-one patients were evaluated and 12 patients (15%) presented with elevated biomarker levels. Compared to controls, they had higher leukocyte (P < .001) and platelet counts (P = .005); higher C-reactive protein (P = .02), and a lower viral load (P = .03). There was no difference according to clinical dengue classification; dengue hemorrhagic fever/dengue shock syndrome severity; duration of symptoms; or prevalence of secondary infection between the 2 groups. Two patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both, and immunohistochemistry for dengue virus showed increased staining on mononuclear cells located in the myocardial tissue. Of the 10 patients who underwent echocardiography, depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another. Cardiac involvement was confirmed by CMR in these 4 patients. CONCLUSIONS  Dengue viruses were shown to cause cardiac disease with clinical manifestations ranging from mild elevation of biomarkers to myocarditis and/or pericarditis.

Association of Longitudinal Changes in Left Ventricular Structure and Function With Myocardial Fibrosis: The Multi-Ethnic Study of Atherosclerosis Study

The association of longitudinal changes in left ventricular (LV) structure and function with myocardial fibrosis is unclear. We relate temporal changes in body size–indexed LV mass (LVMi) and end-diastolic volume indexed to body surface area, LV mass-to-volume ratio, and LV ejection fraction (LVEF) from cine cardiac magnetic resonance for 10 years, with replacement scar assessed from late gadolinium enhancement, and lower postcontrast T1 times reflecting greater diffuse myocardial fibrosis measured at the end of the follow-up period. All participants (n=1813) who underwent cardiac magnetic resonance twice as part of the Multi-Ethnic Study of Atherosclerosis 10 years apart were included. Multivariable logistic and linear regression models adjusted for cardiovascular risk factors measured the association of 10-year changes in LV structure and function, with fibrosis measured at follow-up. The presence of LV scar at year 10 was cross-sectionally associated with higher LVMi (≈10 g/m2), higher mass-to-volume ratio (0.1–0.2 g/mL), but lower LVEF (≈4%) and longitudinally with 3% decrease in LVEF and 0.7% greater end-diastolic volume indexed to body surface area in men for 10 years. Lower postcontrast T1 times at year 10 were associated cross-sectionally with lower LVMi (r=0.33), end-diastolic volume indexed to body surface area (r=0.25), and LVEF (in men only: r=0.14) and longitudinally with a decrease in LVMi (r=0.20) and reduction in LVEF (in men only: r=0.15). Sustained hypertension for 10 years was associated with increased LVMi and higher diffuse and replacement fibrosis at follow-up. During a 10-year period, increased concentric hypertrophy in women and LV dilatation in men were associated with replacement fibrosis, whereas decreasing LVMi was associated with diffuse fibrosis. Hypertension-induced remodeling was related to enhanced replacement and diffuse fibrosis, as well as hypertrophy.

Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study

BACKGROUND Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. OBJECTIVE Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. METHODS Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance, and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2- and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-wave-duration, PR interval, and P-wave axis were automatically measured using 12 SLTM algorithm. PTFV1 was calculated as a product of PPaV1 and PPdV1. RESULTS In linear regression after adjustment for demographic characteristics, body mass index, maximum LA volume index, presence of scar, and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76 mV*ms increase in negative abnormal PTFV1 (95% confidence interval [CI] -1.42 to -0.09; P = .025), 15.3 ms prolongation of PPdV1 (95% CI 6.9 to 23.8; P = .001) and 5.4 ms prolongation of averaged P-duration (95% CI 0.9-10.0; P = .020). LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes and decrease in LA emptying fraction and LA reservoir function. CONCLUSION LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1, and P-duration, but does not affect LA function.

Infiltrated atrial fat characterizes underlying atrial fibrillation substrate in patients at risk as defined by the ARIC atrial fibrillation risk score

BACKGROUND It is known that expanded epicardial fat is associated with atrial fibrillation (AF). However, infiltrated intraatrial fat has not been previously quantified in individuals at risk as determined by the ARIC AF risk score. METHODS Patients in sinus rhythm (N=90, age 57 ± 10 years; 55 men [63.2%]), in 3 groups at risk of AF as determined by the ARIC AF risk score [low (≤ 11 points; n=15), moderate (12-18 points; n=40), high (≥ 19 points; n=23) risk of AF], and paroxysmal AF (n=12) underwent cardiac magnetic resonance study. Intraatrial and epicardial fat was analyzed with a Dark-blood DIR-prepared Fat-Water-separated sequence in the horizontal longitudinal axis. OsiriX DICOM viewer (Geneva, Switzerland) was used to quantify the intraatrial fat area. Width of the cephalad portion of the interatrial septum was measured at the level of the fossa ovalis. RESULTS Intraatrial fat monotonically increased with growing AF risk in study groups (low AF risk 16 ± 4 vs. moderate AF risk 32 ± 18 vs. high AF risk 81 ± 83 mm(2); ANOVA P=0.012). Log-transformed intraatrial fat predicted ARIC AF risk score in multivariate ordered probit regression after adjustment for sex, race, left and right atrial area indices, and body mass index (β-coefficient 0.50 [95% CI 0.03-0.97]; P=0.037), whereas epicardial fat did not. Interatrial septum width showed similar association (3.0 ± 1.4 vs. 5.0 ± 1.8 vs. 7.1 ± 2.7 mm; ANOVA P<0.001; adjusted β-coefficient 2.80 [95% CI 1.19-4.41]; P=0.001). CONCLUSIONS Infiltrated intraatrial fat characterizes evolving substrate in individuals at risk of AF.

Magnetic resonance imaging evaluation of cardiac masses

Background Cardiac tumors are extremely rare; however, when there is clinical suspicion, proper diagnostic evaluation is necessary to plan the most appropriate treatment. In this context, cardiovascular magnetic resonance imaging (CMRI) plays an important role, allowing a comprehensive characterization of such lesions. Objective To review cases referred to a CMRI Department for investigation of cardiac and paracardiac masses. To describe the positive case series with a brief review of the literature for each type of lesion and the role of cardiovascular magnetic resonance imaging in evaluation. Methods Between August 2008 and December 2011, all cases referred for CMRI with suspicion of tumor involving the heart were reviewed. Cases with positive histopathological diagnosis, clinical evolution or therapeutic response compatible with the clinical suspicion and imaging findings were selected. Results Among the 13 cases included in our study, eight (62%) had histopathological confirmation. We describe five benign tumors (myxomas, rhabdomyoma and fibromas), five malignancies (sarcoma, lymphoma, Richter syndrome involving the heart and metastatic disease) and three non-neoplastic lesions (pericardial cyst, intracardiac thrombus and infectious vegetation). Conclusion CMRI plays an important role in the evaluation of cardiac masses of non-neoplastic and neoplastic origin, contributing to a more accurate diagnosis in a noninvasive manner and assisting in treatment planning, allowing safe clinical follow-up with good reproducibility.

Prognostic Implications of Left Ventricular Dyssynchrony for Major Adverse Cardiovascular Events in Asymptomatic Women and Men: The Multi-Ethnic Study of Atherosclerosis

Background Left ventricular (LV) dyssynchrony is related to adverse outcomes in systolic heart failure, but its prognostic importance in asymptomatic population is not known. Our objective was to assess the prognostic implications of LV mechanical dyssynchrony in a large multiethnic population before the occurrence of global LV dysfunction. Methods and Results A total of 1392 participants in the Multi‐Ethnic Study of Atherosclerosis (MESA; mean age: 64.7 years; 46% were women) with cardiac magnetic resonance imaging at baseline were followed for a median duration of 8.3 years. Harmonic phase imaging analysis was used to derive systolic circumferential strain. Greater standard deviation of time to peak systolic strain (SD‐TPS) indicates greater dyssynchrony. With SD‐TPS as a continuous variable, Cox proportional hazards analysis was used to assess hazards ratio after adjusting for demographics, cardiovascular risk factors, LV mass‐to‐volume ratio, and ejection fraction. Using the 75th percentile of SD‐TPS as a cutoff, Kaplan–Meier analysis was performed between 2 categorical groups for each gender. Higher values of dyssynchrony in women predicted major adverse cardiovascular events, defined as myocardial infarction, heart failure, stroke, and death (hazard ratio: 1.01 per 1‐ms increment in SD‐TPS, P=0.015), hard coronary events (hazard ratio: 1.05 per 1‐ms increment in SD‐TPS, P=0.026), and cerebrovascular events (hazard ratio: 1.03 per 1‐ms increment in SD‐TPS, P=0.013). In contrast, dyssynchrony in men was not predictive of events. Kaplan–Meier analyses in women revealed increased event occurrence in the higher dyssynchrony group, but this was not the case in men. Conclusions In an asymptomatic cohort, greater LV dyssynchrony determined by cardiac magnetic resonance imaging predicts adverse cardiovascular outcome in women but not in men. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00005487.

Association of Subclinical Atherosclerosis Using Carotid Intima-Media Thickness, Carotid Plaque, and Coronary Calcium Score with Left Ventricular Dyssynchrony: The Multi-Ethnic Study of Atherosclerosis

BACKGROUND The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. METHODS AND RESULTS Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min. CONCLUSION In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block.

Electrocardiographic Impact of Myocardial Diffuse Fibrosis and Scar: MESA (Multi-Ethnic Study of Atherosclerosis).

Purpose To examine the associations of myocardial diffuse fibrosis and scar with surface electrocardiographic (ECG) parameters in individuals free of prior coronary heart disease in four different ethnicities. Materials and Methods This prospective cross-sectional study was approved by the institutional review boards, and all participants gave informed consent. A total of 1669 participants in the Multi-Ethnic Study of Atherosclerosis, or MESA, who were free of prior myocardial infarction underwent both ECG and cardiac magnetic resonance imaging. In individuals without a late gadolinium enhancement-defined myocardial scar (n = 1131), T1 mapping was used to assess left ventricular (LV) interstitial diffuse fibrosis. The associations of LV diffuse fibrosis or myocardial scar with ECG parameters (QRS voltage, QRS duration, and corrected QT interval [QTc]) were evaluated by using multivariable regression analyses adjusted for demographic data, risk factors for scar, LV end-diastolic volume, and LV mass. Results The mean age of the 1669 participants was 67.4 years ± 8.7 (standard deviation); 49.8% were women. Lower postcontrast T1 time at 12 minutes was significantly associated with lower QRS Sokolow-Lyon voltage (β = 15.1 µV/10 msec, P = .004), lower QRS Cornell voltage (β = 9.2 µV/10 msec, P = .031), and shorter QRS duration (β = 0.16 msec/10 msec, P = .049). Greater extracellular volume (ECV) fraction was also significantly associated with lower QRS Sokolow-Lyon voltage (β = -35.2 µV/1% ECV increase, P < .001) and Cornell voltage (β = -23.7 µV/1% ECV increase, P < .001), independent of LV structural indexes. In contrast, the presence of LV scar (n = 106) was associated with longer QTc (β = 4.3 msec, P = .031). Conclusion In older adults without prior coronary heart disease, underlying greater LV diffuse fibrosis is associated with lower QRS voltage and shorter QRS duration at surface ECG, whereas clinically unrecognized myocardial scar is associated with a longer QT interval.

Evaluation of Right Ventricular Systolic Function in Chagas Disease Using Cardiac Magnetic Resonance ImagingCLINICAL PERSPECTIVE

Background— Right ventricular (RV) impairment is postulated to be responsible for prominent systemic congestion in Chagas disease. However, occurrence of primary RV dysfunction in Chagas disease remains controversial. We aimed to study RV systolic function in patients with Chagas disease using cardiac magnetic resonance. Methods and Results— This cross-sectional study included 158 individuals with chronic Chagas disease who underwent cardiac magnetic resonance. RV systolic dysfunction was defined as reduced RV ejection fraction based on predefined cutoffs accounting for age and sex. Multivariable logistic regression was used to verify the relationship of RV systolic dysfunction with age, sex, functional class, use of medications for heart failure, atrial fibrillation, and left ventricular systolic dysfunction. Mean age was 54±13 years, 51.2% men. RV systolic dysfunction was identified in 58 (37%) individuals. Although usually associated with reduced left ventricular ejection fraction, isolated RV systolic dysfunction was found in 7 (4.4%) patients, 2 of them in early stages of Chagas disease. Presence of RV dysfunction was not significantly different in patients with indeterminate/digestive form of Chagas disease (35.7%) compared with those with Chagas cardiomyopathy (36.8%) (P=1.000). Conclusions— In chronic Chagas disease, RV systolic dysfunction is more commonly associated with left ventricular systolic dysfunction, although isolated and early RV dysfunction can also be identified.

Subclinical Myocardial Disease in Heart Failure Detected by CMR

Noninvasive cardiac imaging plays a central role in the assessment of patients with heart failure at all stages of disease. Moreover, this role can be even more important for individuals with asymptomatic cardiac functional or structural abnormalities―subclinical myocardial disease ― because they could have benefits from early interventions before the onset of clinical heart failure. In this sense, cardiac magnetic resonance offers not only precise global cardiac function and cardiac structure, but also more detailed regional function and tissue characterization by recent developing methods. In this section, some of the main methods available for subclinical myocardial disease detection are reviewed in terms of what they can provide and how they can improve heart failure assessment.