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Electrocardiographic (ECG) abnormalities are frequently identified in Chronic Chagas cardiomyopathy (CCC) patients and advanced abnormalities are related to a worse prognosis. Cardiac Magnetic Resonance (CMR) can precisely assess ventricular systolic dysfunction and quantify myocardial fibrosis (MF), both identified as prognostic factors. We sought to investigate if ECG abnormalities in CCC patients were associated with more severe myocardial involvement as evaluated by CMR.Methods: CCC patients with 12‑lead ECG and CMR closely obtained were included. ECG analysis evaluated rhythm, presence, and type of intraventricular conduction disturbances (IVCD) and, ventricular premature beats (VPB). CMR short-axis cine and late gadolinium enhancement images were evaluated to obtain left and right ventricular ejection fractions and MF mass, respectively. Statistical significance was set in 5%.Results: 194 CCC patients (98 women, 56 ± 14 years) were evaluated, and no IVCD was detected in 71. The most common IVCD was the association of right bundle branch block and left anterior fascicular block (RBBB+LAFB) in 58 patients, followed by isolated RBBB in 34, isolated LAFB in 17, and left bundle branch block (LBBB) in 14 patients. Of patients with no IVCD, 63% had MF and the burden of fibrosis (no IVCD - 7.4 ± 8.6%; RBBB - 6.6 ± 6.5%; p = 1.00), as well as left ventricular ejection fraction (LVEF) (no IVCD - 52 ± 14%; RBBB - 55 ± 10%; p = 1.00) were similar to patients with isolated RBBB. Left conduction system impairment was associated with lower LVEF (LAFB - 39 ± 15%; RBBB+LAFB- 41 ± 15%; and LBBB - 35 ± 15%; p < 0.001) and more MF (RBBB+LAFB - 12.2 ± 10.4%; LBBB - 10.6 ± 7.5%; and LAFB - 12.0 ± 7.0%; p < 0.001). The univariable model showed that the presence of MF was related to RBBB+LAFB (OR 5.0; p = 0.001) and VPB (OR 6.3; p = 0.014). After adjustment for age, gender, and different risk factors in a multivariable model, the same findings were still significantly related to CMR myocardial fibrosis (RBBB+LAFB OR 5.0; p = 0.002 / VPB OR 6.9; p = 0.015).Conclusions: ECG without IVCD does not exclude serious cardiac abnormalities in CCC, and isolated RBBB seems to have a benign course. The presence of VPB and left branch conduction impairment, especially LAFB associated with RBBB, indicate a more severe cardiac involvement. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine feasibility, reference intervals, and reproducibility of left ventricular ejection fraction (LVEF) and speckle‐tracking echocardiography (STE) in adult Syrian hamsters. Background: Syrian hamster is an experimental model for several heart diseases. Echocardiography allows the evaluation of structure and function with bidimensional conventional techniques and STE. However, there is no data regarding reference values for bidimensional LVEF and myocardial strain in hamsters. Methods: A total of 135 female Syrian hamsters were anesthetized and studied with a small animal dedicated echocardiography system. Echocardiography measurements were obtained from M‐mode and B‐mode images. Feasibility and 95% reference intervals were obtained for LVEF using three different approaches: LVEF_Teichholz (from M‐mode linear measurements), LVEF_BMode (from area‐length method), and LVEF_ STE (from strain), and for global longitudinal (GLS), circumferential (GCS), and radial (GRS) endocardial strain. Reproducibility was assessed as intra‐class correlation coefficients. Results: Feasibility of LVEF and endocardial strain was high (95% in FEVE_Teichholz, 93% in the LVEF_BMode, 84% in the LVEF_STE, 84% from PSLAX, and 80% from PSSAX). Values of LVEF_Teichholz were significantly higher than values of LVEF_BMode, and LVEF_STE‐derived methods (59.0 ± 5.8, 53.8 ± 4.7, 46.3 ± 5.7, p < 0.0001). The 95% reference intervals for GLS, GCS, and GRS were respectively −13.6(−7.5;‐20.4)%, −20.5 ± 3.1%, and + 34,7 ± 7.0%. Intra‐class correlation coefficients were 0.49 – 0.91 for LVEF measurements, 0.73 – 0.92 for STE, with better results for LVEF_Teichholz and GLS. Conclusions: Evaluation of LVEF by several methods and STE parameters is feasible in hamsters. Reference intervals for LVEF and STE obtained for this experimental animal model can be applied at future research. [ABSTRACT FROM AUTHOR]

Recent evidence links long-term (visit-to-visit) blood pressure (BP) variability to the risk of cardiovascular disease, independent of mean BP levels. Potential associations between long-term BP variability and cardiovascular disease risk may be reflected in early life course alterations in coronary artery calcium (CAC) and carotid intima-media thickness. We evaluated 2482 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean [SD] age at the year 20 exam [2005-2006] was 45.4 [3.6] years, 43.2% men, and 41.3% black). We included participants with BP assessments across 20-years (year 0, 2, 5, 7, 10, 15, 20 exams) and carotid intima-media thickness and CAC data at the year 20 exam. BP variability was assessed using variability independent of the mean and SD. Adjusted multivariable linear or logistic regression models (as appropriate) were used to assess associations between long-term BP variability measures and carotid intima-media thickness. and CAC (ln [CAC+1] and prevalent CAC). Long-term systolic BP variability independent of the mean (per 1 SD) was positively associated with carotid intima-media thickness (β=10 μm, SE=3, P=0.002). Similarly, long-term diastolic BP variability independent of the mean was associated with carotid intima-media thickness (β=10 μm, SE (3), P=0.001). Long-term BP variability was not associated with either ln [CAC+1] or prevalent CAC. Long-term systolic and diastolic BP variability across early adulthood was positively associated with modest adverse midlife alterations in carotid intima-media thickness but not to CAC. Our findings provide further insights into pathophysiologic mechanisms that link long-term BP variability to cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aims: The long‐term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. Methods and results: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long‐term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year‐25 exam (2010–2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year‐0 exam (1985–1986), 57.4% were women, and 41.9% were African‐American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of <1, 1–2, 3–4, and >4 cups/day with non‐coffee drinkers were β = −0.30%, P < 0.05; β = −0.35%, P < 0.05; β = −0.32%, P < 0.05; β = −0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of <1, 1–2, 3–4, and >4 cups/day with non‐coffee drinkers were β = −0.29, P < 0.05; β = −0.38, P < 0.01; β = −0.20, P >.05; and β = −0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (β = −1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all). Conclusions: Low‐to‐moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function. [ABSTRACT FROM AUTHOR]

Aims Left ventricular (LV) ejection fraction (LVEF) is an extensively utilized marker of LV function that is often interpreted without recourse to alterations in LV geometry and hypertrophy. LV global function index (LVGFI) is a novel marker that incorporates LV structure in the assessment of LV cardiac performance. We evaluated the prognostic utility of LVGFI from young adulthood into middle age for incident heart failure (HF) and cardiovascular disease (CVD) in comparison to LVEF. Methods and results Included were 4107 CARDIA participants with echocardiograms in Year-5 (1990–1991). LVGFI was defined as LV stroke volume/LV global volume*100, where LV global volume was the sum of the LV mean cavity volume ((LV end-diastolic volume + LV end-systolic volume)/2) and myocardial volume (LV mass/density). Adjusted Cox proportional hazard models were utilized to predict incident HF and CVD outcomes. Mean age of participants was 29.8 ± 3.7 years, 55% female, and 48.7% black. Higher body mass index [beta coefficient (B) = −0.11 standard error (SE) = 0.02, P  <   0.001], higher blood pressure (B = −0.04, SE = 0.01, P  <   0.01), smoking (B = −0.82, SE = 0.22, P  < 0.001), male sex (P  < 0.001), and black race (P  < 0.001) were associated with worse LVGFI. A total of 207 incident CVD events were observed over the course of 98 035 person-years at risk. Higher LVGFI was associated with HF, hazard ratio (HR) = 0.70, 95% confidence interval (CI) (0.54–0.91), hard CVD HR = 0.83, 95% CI (0.71–0.96), and all CVD HR = 0.83, 95% CI (0.72–0.96). For HF outcomes, Harrell's C -statistic for LVGFI (0.80) was greater than LVEF (0.66). Conclusion LVGFI is a strong, independent predictor of incident HF and CVD that provides incremental prognostic value compared with LVEF. Male sex, black race, obesity, hypertension, and smoking are associated with worse LVGFI in the early adult lifespan. [ABSTRACT FROM AUTHOR]

Aims To evaluate the association of cumulative blood pressure (BP) from young adulthood to middle age with left atrial (LA) structure/function as assessed by three-dimensional echocardiography (3DE) in a large longitudinal bi-racial population study. Methods and results We conducted a prospective post hoc analysis of individuals enrolled at the Coronary Artery Risk Development in Young Adults, which is a multi-centre bi-racial cohort with 30 years of follow-up. Cumulative systolic and diastolic BP levels were defined by summing the product of average millimetres of mercury and the years between each two consecutive clinic visits over 30 years of follow-up. Multivariable linear regression analyses were used to assess the relationship between cumulative systolic and diastolic BP with 3DE LA structure and function, adjusting for demographics and traditional cardiovascular risk factors. A total of 1033 participants were included, mean age was 55.4 ± 3.5 years, 55.2% women, 43.9% blacks. Cumulative systolic BP had stronger correlations than cumulative diastolic BP. Higher cumulative systolic BP was independently associated with higher 3D LA volumes: maximum (β  = 1.74, P  = 0.004), pre-atrial contraction (β  = 1.87, P  < 0.001), minimum (β  = 0.76, P  = 0.04), total emptying (β  = 0.98, P  = 0.006), active emptying (β  = 1.12, P  < 0.001), and lower magnitude 3D LA early diastolic strain rate (β  = 0.05, P  = 0.02). Higher cumulative diastolic BP was independently associated with higher 3D LA active emptying volume (β  = 0.66, P  = 0.002), lower magnitude 3D LA early diastolic strain rate (β  = 0.05, P  = 0.004), and higher magnitude 3D LA late diastolic strain rate (β  = −0.04, P  = 0.05). Conclusion Higher cumulative BP from early adulthood throughout middle age was associated with adverse LA remodelling evaluated by 3D echocardiography. [ABSTRACT FROM AUTHOR]

The relationship of metabolic syndrome (MetS) and insulin resistance (one of its key pathophysiological mediators) with diastolic dysfunction and myocardial fibrosis is not well understood. This study aimed to evaluate the association of MetS with diastolic function and myocardial extracellular matrix (ECM) using cardiac MRI (CMRI) in a large community-based population. This cross-sectional analysis included 1,582 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with left ventricular ejection fraction ≥50% and no history of cardiac events. Diastolic function was assessed using tagged CMRI parameters including end-diastolic strain rate (EDSR) and strain relaxation index (SRI). ECM was evaluated using extracellular volume (ECV) quantification. Participants' mean age was 67.4 ± 8.6 years, and 48.1% were males. MetS was present in 533 individuals (33.7%), and type 2 diabetes in 250 (15.8%). In the multivariable analyses, MetS (irrespective of the presence of type 2 diabetes) and higher insulin resistance were associated with impaired diastolic function (higher SRI and lower EDSR), independent of ECV. In conclusion, MetS, irrespective of the presence of type 2 diabetes, was independently associated with impaired diastole. These functional myocardial changes seem to result from intrinsic cardiomyocyte alterations, irrespective of the myocardial interstitium (including fibrosis). [ABSTRACT FROM AUTHOR]

Right ventricle (RV) is considered a neglected chamber in cardiology and knowledge about its role in cardiac function was mostly focused on ventricular interdependence. However, progress on the understanding of myocardium diseases primarily involving the RV led to a better comprehension of its role in health and disease. In Chagas disease (CD), there is direct evidence from both basic and clinical research of profound structural RV abnormalities. However, clinical detection of these abnormalities is hindered by technical limitations of imaging diagnostic tools. Echocardiography has been a widespread and low-cost option for the study of patients with CD but, when applied to the RV assessment, faces difficulties such as the absence of a geometrical shape to represent this cavity. More recently, the technique has evolved to a focused guided RV imaging and myocardial deformation analysis. Also, cardiac magnetic resonance (CMR) has been introduced as a gold standard method to evaluate RV cavity volumes. CMR advantages include precise quantitative analyses of both LV and RV volumes and its ability to perform myocardium tissue characterization to identify areas of scar and edema. Evolution of these cardiac diagnostic techniques opened a new path to explore the pathophysiology of RV dysfunction in CD. [ABSTRACT FROM AUTHOR]

Microvascular perfusion disturbance (MPD) is common in chronic Chagas cardiomyopathy (CCC) and may cause myocardial damage. Pentoxifylline (PT) is a phosphodiesterase inhibitor with anti-inflammatory properties that may lead to reduction of inflammation and MPD and attenuate the progression of the myocardial dysfunction in CCC. We investigated 3 groups of hamsters: controls and treated with saline (CO, n=9), infected with T. cruzi and treated with saline (CH+SL, n=12), infected and treated with PT (CH+PT, n=12). After 6 months of infection and 60 days of PT (20 mg/kg/day, ip) or saline, the animals were submitted to echocardiography and to rest Sestamibi-Tc99m SPECT myocardial perfusion scintigraphy (MPS). The area of myocardial perfusion defects (PD) was assessed through the calculation of polar maps. After euthanasia, we performed a histopathological study of cardiac inflammation and gene expression of TNF-α. At baseline all groups showed similar areas of PD (CO: 0.0±0.0%, CH+SL:0.8±1.6%, CH+PT:1.9±3.0%, p>0.05) and LVEF (CO:53.4±5.6%, CH+SL:47.0±10.1%, CH+PT:53.9±6.5%, p>0.05). After treatment, there was a significant increase of the PD only in the CH+SL group (0.8±1.6 to 9.4±9.7%, p>0.05), and CH+PT animals exhibited PD area similar to CO animals 2.7±2.7% and 0.0±0.0%, respectively (p>0.05). Similar decrease of LVEF was seen in both infected groups: (CH+SL:40.0±13.7% and CH+PT:42.7±9.0%). No change of the LVEF was observed in CO (53.4±5.6%). Quantitative histological analysis revealed a larger number of nuclei of mononuclear inflammatory cells in CH+SL, 615.1±133.0 cel/mm² and CH+PT groups, 395.7±88.3 cel/mm² when compared to CO, 193.0 ± 25.7 cel/mm², p<0.001. A higher number of inflammatory cells was found in the CH+SL group when compared to the CH+PT group, p<0.001. TNF-α expression was higher in the CH+SL group (2.5±1.7) when compared to the CO (0.9±0.4), but similar to the CH+PT (2.4±1.7), p>0.9. There was a moderate correlation between PD and inflammatory cells (R=0.6) and LVEF (R=-0.7), p<0.0001 for both; and between LVEF and inflammatory cells (R=-0.4, p=0.01). The prolonged use of PT in CCC animals was effective in reducing inflammation and progression of MPD evaluated in vivo. However, PT did not prevent the progression of left ventricular systolic dysfunction in this model. These results suggest that PD may represent a surrogate marker for inflammation and its potential use to monitor disease progression. [ABSTRACT FROM AUTHOR]

Accurate assessment of the physical capacity limitation is a pivotal issue during evaluation of chronic heart failure patients, as symptomatic patients are candidates to medical therapy optimization and devices implantation. We tested the hypothesis that use of Specific Activity Scale (SAS) is more accurate in identifying patients with mild functional class (FC) limitation as compared to the classical NYHA FC assessment approach. We prospectively investigated 101 adult patients with chronic heart failure with reduced ejection fraction followed in an outpatient clinic of a tertiary hospital [age = 56.0±12.3 y; 59% males; LVEF = 29.2 ± 9.2%; with different etiologies: dilated cardiomyopathy (30%), ischemic (28%), hypertension (20%) and Chagas disease (10%)]. Patients underwent FC evaluation by using the NYHA classification and the SAS approach, and to cardio-pulmonar exercise test (CPET), with measurement of peak-VO 2. Different experienced investigators separately performed each test and were blinded regarding the results of other evaluations. We calculated the Net Reclassification index comparing the SAS and NYHA, taking as gold-standard the result of the peak-VO 2 in the CPET. Table 1 summarizes the results. We observed a higher proportion of FC I detection by using NYHA method, as compared to the other approaches. According to the results of the NYHA, 24 patients (24%) were deemed as FC I. The use of SAS in this same group patient group detected a significantly smaller proportion of FC I patients [n = 6 (6%), McNemar test, p = 0,00002]. Among the 18 patients reclassified as non-FC I, by using of SAS , most of them (N=16; 89%) were in accordance with the CPT results. In an outpatient cohort of chronic HF patients, FC assessment by NYHA overestimates the proportion of asymptomatic FC I patients, as compared to the results of the CPET. The use of SAS approach may correctly reclassify most of those patients, providing more accurate identification of symptomatic patients that are candidates to medical therapy optimization and/or device implantation. [ABSTRACT FROM AUTHOR]