Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial.

PURPOSE: Patients with chronic chagasic cardiomyopathy with preserved ventricular function present with autonomic imbalance. This study evaluated the effects of exercise training (ET) in restoring peripheral and cardiac autonomic control and skeletal muscle phenotype in patients with subclinical chronic chagasic cardiomyopathy. METHODS: This controlled trial (NCT02295215) included 24 chronic chagasic cardiomyopathy patients who were randomized www.random.org/lists/ into two groups: those who underwent exercise training (n = 12) and those who continued their usual activities (n = 12). Eight patients completed the exercise training protocol, and 10 patients were clinically followed up for 4 months. Muscular sympathetic nerve activity was measured by microneurography and muscle blood flow (MBF) using venous occlusion plethysmography. The low-frequency component of heart rate variability in normalized units (LFnuHR) reflects sympathetic activity in the heart, and the low-frequency component of systolic blood pressure variability in normalized units reflects sympathetic activity in the vessels. The infusion of vasoactive drugs (phenylephrine and sodium nitroprusside) was used to evaluate cardiac baroreflex sensitivity, and a vastus lateralis muscle biopsy was performed to evaluate atrogin-1 and MuRF-1 gene expression. RESULTS: The baroreflex sensitivity for increases (p = 0.002) and decreases (p = 0.02) in systolic blood pressure increased in the ET group. Muscle blood flow also increased only in the ET group (p = 0.004). Only the ET group had reduced resting muscular sympathetic nerve activity levels (p = 0.008) and sympathetic activity in the heart (LFnu; p = 0.004) and vessels (p = 0.04) after 4 months. Regarding skeletal muscle, after 4 months, participants in the exercise training group presented with lower atrogin-1 gene expression than participants who continued their activities as usual (p = 0.001). The reduction in muscular sympathetic nerve activity was positively associated with reduced atrogin-1 (r = 0.86; p = 0.02) and MuRF-1 gene expression (r = 0.64; p = 0.06); it was negatively associated with improved baroreflex sensitivity both for increases (r = -0.72; p = 0.020) and decreases (r = -0.82; p = 0.001) in blood pressure. CONCLUSIONS: ET improved cardiac and peripheral autonomic function in patients with subclinical chagasic cardiomyopathy. ET reduced MSNA and sympathetic activity in the heart and vessels and increased cardiac parasympathetic tone and baroreflex sensitivity. Regarding peripheral muscle, after 4 months, patients who underwent exercise training had an increased cross-sectional area of type I fibers and oxidative metabolism of muscle fibers, and decreased atrogin-1 gene expression, compared to participants who continued their activities as usual. In addition, the reduction in MSNA was associated with improved cardiac baroreflex sensitivity, reduced sympathetic cardiovascular tone, and reduced atrogin-1 and MuRF-1 gene expression. TRIAL REGISTRATION: ID: NCT02295215. Registered in June 2013.

Usefulness of speckle tracking echocardiography and biomarkers for detecting acute cellular rejection after heart transplantation.

BACKGROUND: Acute cellular rejection (ACR) is a major complication after heart transplantation. Endomyocardial biopsy (EMB) remains the gold standard for its diagnosis, but it has concerning complications. We evaluated the usefulness of speckle tracking echocardiography (STE) and biomarkers for detecting ACR after heart transplantation. METHODS: We prospectively studied 60 transplant patients with normal left and right ventricular systolic function who underwent EMB for surveillance 6 months after transplantation. Sixty age- and sex-matched healthy individuals constituted the control group. Conventional echocardiographic parameters, left ventricular global longitudinal, radial and circumferential strain (LV-GLS, LV-GRS and LV-GCS, respectively), left ventricular systolic twist (LV-twist) and right ventricular free wall longitudinal strain (RV-FWLS) were analyzed just before the procedure. We also measured biomarkers at the same moment. RESULTS: Among the 60 studied patients, 17 (28%) had severe ACR (grade ≥ 2R), and 43 (72%) had no significant ACR (grade 0 - 1R). The absolute values of LV-GLS, LV-twist and RV-FWLS were lower in transplant patients with ACR degree ≥ 2 R than in those without ACR (12.5% ± 2.9% vs 14.8% ± 2.3%, p=0.002; 13.9° ± 4.8° vs 17.1° ± 3.2°, p=0.048; 16.6% ± 2.9% vs 21.4%± 3.2%, p < 0.001; respectively), while no differences were observed between the LV-GRS or LV-GCS. All of these parameters were lower in the transplant group without ACR than in the nontransplant control group, except for the LV-twist. Cardiac troponin I levels were significantly higher in patients with significant ACR than in patients without significant ACR [0.19 ng/mL (0.09-1.31) vs 0.05 ng/mL (0.01-0.18), p=0.007]. The combination of troponin with LV-GLS, RV-FWLS and LV-Twist had an area under curve for the detection of ACR of 0.80 (0.68-0.92), 0.89 (0.81-0.93) and 0.79 (0.66-0.92), respectively. CONCLUSION: Heart transplant patients have altered left ventricular dynamics compared with control individuals. The combination of troponin with strain parameters had higher accuracy for the detection of ACR than the isolated variables and this association might select patients with a higher risk for ACR who will benefit from an EMB procedure in the first year after heart transplantation.

Right Ventricular Systolic Function After the Cone Procedure for Ebstein's Anomaly: Comparison Between Echocardiography and Cardiac Magnetic Resonance.

Although the Cone procedure has improved outcomes for patients with Ebstein´s anomaly (EA), neither RV systolic function recovery in long-term follow-up nor the best echocardiographic parameters to assess RV function are well established. Thus, we evaluated RV performance after the Cone procedure comparing two-dimensional (2DEcho) and three-dimensional (3DEcho) echocardiography to cardiac magnetic resonance (CMR). We assessed 27 EA patients after the Cone procedure (53% female, median age of 20 years at the procedure, median post-operative follow-up duration of 8 years). Echocardiography was performed 4 h apart from the CMR. RV global longitudinal strain (GLS), fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index and tissue Doppler S' velocity were assessed using 2DEcho, whereas 3DEcho was used to evaluate RV volumes and ejection fraction (RVEF). Echocardiographic variables were compared to CMR-RVEF. All patients were in the NYHA functional class I. Median TAPSE was 15.9 mm, FAC 30.2%, and RV-GLS -15%; median RVEF by 3DEcho was 31.9% and 43% by CMR. Among 2DEcho parameters, RV-GLS and FAC had a substantial correlation with CMR-RVEF (r = - 0.63 and r = 0.55, respectively); from 3DEcho, the indexed RV volumes and RVEF were closely correlated with CMR (RV-EDVi, r = 0.60, RV-ESVi, r = 0.72; and RVEF r = 0.60). RV systolic function is impaired years after the Cone procedure, despite a good clinical status. FAC and RV-GLS are useful 2DEcho tools to assess RV function in these patients; however, 3DEcho measurements appear to provide a better RV assessment.

Relation of mitral valve morphology to surgical repair results in patients with mitral valve prolapse: A three-dimensional transesophageal echocardiography study.

BACKGROUND: The identification of predictors of mitral valve (MV) repair results is important for quality improvement in cardiac surgery. The aim of this study was to evaluate the relationship between MV morphological quantification by three-dimensional (3D) transesophageal echocardiography and mitral repair results. METHODS: Fifty-four patients with MV prolapse who were submitted to surgical repair were divided into 2 groups according to their postoperative mitral regurgitation (MR) degree (group 1, grade 0-I MR; group 2, ≥grade II MR). Morphological parameters related to the mitral ring, dimension of leaflets and prolapse, coaptation line, distance from papillary muscles to the leaflet border and valve angles were analyzed by 3D MV quantification. Cardiac remodeling and MR quantitative parameters were also evaluated. RESULTS: There was no correlation between 3D MV quantification and surgical results; a multivariate analysis did not show an association between morphological parameters and surgical outcome. The distance from the posteromedial papillary muscle to the leaflet border was higher (P = .038) in patients with ≥grade II postoperative MR. The left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic and end-systolic volumes were larger in patients with a significant residual MR (P < .05). CONCLUSION: Three-dimensional MV quantification did not predict the postoperative MR grade; however, the distance from the posteromedial papillary muscles to the leaflet border may be related to suboptimal repair results. Furthermore, excessive cardiac remodeling was related to postoperative MR ≥ grade II, what could suggest a potential benefit of early surgical treatment.

Exercise Training on Anginal Threshold Does Not Improve Endothelial Function in Refractory Angina Patients.

Refractory angina (RA) is a chronic condition of coronary artery disease (CAD). Endothelial function (EF) measured by flow-mediated dilation (FMD) is an important prognostic marker in CAD. Exercise training is a stimulus that improves EF in CAD. However, exercise training effects on EF in RA are unknown. Therefore, we aimed to verify the effects of exercise training on EF in RA. This was a longitudinal, non-randomized clinical study, involving patients with patients limited by angina, aged 45 to 75 years. Patients were prospectively allocated by convenience to either exercise trained (ET) or control group (C). Laboratory analysis, cardiopulmonary exercise test (CPET), and FMD were implemented at inclusion and after 12 weeks of exercise training or clinical treatment period. Exercise training included 60 minutes per session, 3 times a week, including 40 minutes of aerobic exercise on anginal threshold heart rate obtained on the CPET, 15 minutes of resistance training, and 5 minutes of stretching. A total of 38 patients were included (mean age 60 ± 9 years, 22 men); 21 were allocated to the ET and 17 to the C group. Baseline measures showed no differences between groups. After 12 weeks glycated hemoglobin and systolic blood pressure were lower in ET before than ET after (p = 0.004, and p = 0.05, respectively), and exercise time of the CPET was lower in ET before than ET after (p = 0.002). Exercise training did not change FMD. In conclusion, exercise training performed on anginal threshold increases exercise tolerance but causes no changes in EF in patients with RA.

Risk prediction in patients with classical low-flow, low-gradient aortic stenosis undergoing surgical intervention.

Introduction: Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. Methods: This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm2, mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. Results: All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). Conclusions: In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification.

Objectives: The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS). Background: Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS. Methods: Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median. Results: 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3. Conclusions: Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.

New equation for prediction of reverse remodeling after cardiac resynchronization therapy.

OBJECTIVES: To integrate data from two-dimensional echocardiography (2D ECHO), three-dimensional echocardiography (3D ECHO), and tissue Doppler imaging (TDI) for prediction of left ventricular (LV) reverse remodeling (LVRR) after cardiac resynchronization therapy (CRT). It was also compared the evaluation of cardiac dyssynchrony by TDI and 3D ECHO. METHODS: Twenty-four consecutive patients with heart failure, sinus rhythm, QRS ≥ 120 msec, functional class III or IV and LV ejection fraction (LVEF) ≤ 0.35 underwent CRT. 2D ECHO, 3D ECHO with systolic dyssynchrony index (SDI) analysis, and TDI were performed before, 3 and 6 months after CRT. Cardiac dyssynchrony analyses by TDI and SDI were compared with the Pearson's correlation test. Before CRT, a univariate analysis of baseline characteristics was performed for the construction of a logistic regression model to identify the best predictors of LVRR. RESULTS: After 3 months of CRT, there was a moderate correlation between TDI and SDI (r = 0.52). At other time points, there was no strong correlation. Nine of twenty-four (38%) patients presented with LVRR 6 months after CRT. After logistic regression analysis, SDI (SDI > 11%) was the only independent factor in the prediction of LVRR 6 months of CRT (sensitivity = 0.89 and specificity = 0.73). After construction of receiver operator characteristic (ROC) curves, an equation was established to predict LVRR: LVRR =-0.4LVDD (mm) + 0.5LVEF (%) + 1.1SDI (%), with responders presenting values >0 (sensitivity = 0.67 and specificity = 0.87). CONCLUSIONS: In this study, there was no strong correlation between TDI and SDI. An equation is proposed for the prediction of LVRR after CRT. Although larger trials are needed to validate these findings, this equation may be useful to candidates for CRT.

Early Change in Area Strain Detected by 3D Speckle Tracking Is Associated With Subsequent Cardiotoxicity in Patients Treated With Low Doses of Anthracyclines.

Objective: To evaluate the prognostic impact of the parameters of myocardial deformation using three-dimensional speckle tracking echocardiography (3DSTE) in patients with breast cancer who underwent chemotherapy with low doses of anthracyclines. Background: Chemotherapy-related cardiotoxicity has an important prognostic impact on cancer survivors. Three-dimensional STE has revealed more consistent data than two-dimensional techniques and may represent a more accurate tool in the evaluation of myocardial function in patients who underwent chemotherapy. Methods: We evaluated patients with breast cancer who were treated with anthracyclines (associated or not with trastuzumab) in five stages: baseline, after cumulative doses of 120 and 240 mg/m2 of doxorubicin, and then, after 6 months and at least 1 year after anthracyclines. Ultrasensitive troponin I (US-TnI) and a standard echocardiography study were performed at each stage. We analyzed left ventricular ejection fraction (LVEF) by Simpson's method, two-dimensional speckle tracking (2DSTE) with longitudinal and radial strain values, and 3DSTE with longitudinal, radial, and circumferential strain as well as twist, torsion, rotation, and three-dimensional global area strain (3DGAS). Cardiotoxicity was defined as a decrease in LVEF by more than 10 percentage points to a value lower than 53%. Results: We evaluated 51 female patients who were aged 50.6 ± 11 years. After the cumulative dose of 240 mg/m2 of doxorubicin, US-TnI was increased (>34 pg/ml) in 21 patients (45%, p > 0.001), LVEF remained unchanged (p = 0.178), while 2DSTE longitudinal strain was decreased (from -17.8% to -17.1%, p < 0.001) and 3DSTE detected changes in longitudinal, radial, circumferential, and area strain. After a lower cumulative dose of doxorubicin (120 mg/m2), 3DGAS (p < 0.001) was the only parameter that was changed. In the follow-up, 7 (13%) patients presented a decrease in LVEF. Three-dimensional GAS early changed to abnormal values was the only variable associated with a subsequent decrease in LVEF (definitive cardiotoxicity). Conclusion: In patients with breast cancer, 3DSTE detected early changes in area strain after very low doses of doxorubicin. The 3DGAS early changed to abnormal values was associated with a subsequent decrease in LVEF, representing a promising technique to predict chemotherapy-induced cardiomyopathy.

Cardiopulmonary exercise test in patients with refractory angina: functional and ischemic evaluation.

OBJECTIVES: Refractory angina (RA) is a chronic condition clinically characterized by low effort tolerance; therefore, physical stress testing is not usually requested for these patients. Cardiopulmonary exercise testing (CPET) is considered a gold standard examination for functional capacity evaluation, even in submaximal tests, and it has gained great prominence in detecting ischemia. The authors aimed to determine cardiorespiratory capacity by using the oxygen consumption efficiency slope (OUES) in patients with refractory angina. The authors also studied the O2 pulse response by CPET and the association of ischemic changes with contractile modifications by exercise stress echocardiography (ESE). METHODS: Thirty-one patients of both sexes, aged 45 to 75 years, with symptomatic (Canadian Cardiovascular Society class II to IV) angina who underwent CPET on a treadmill and exercise stress echocardiography on a lower limb cycle ergometer were studied. ClinicalTrials.gov: NCT03218891. RESULTS: The patients had low cardiorespiratory capacity (OUES of 1.74 ± 0.4 L/min; 63.9±14.7% of predicted), and 77% of patients had a flattening or drop in O2 pulse response. There was a direct association between Heart Rate (HR) at the onset of myocardial ischemia detected by ESE and HR at the onset of flattening or drop in oxygen pulse response detected by CPET (R = 0.48; p = 0.019). CONCLUSION: Patients with refractory angina demonstrate low cardiorespiratory capacity. CPET shows good sensitivity for detecting abnormal cardiovascular response in these patients with a significant relationship between flattening O2 pulse response during CEPT and contractile alterations detected by exercise stress echocardiography.

Real-time three-dimensional echocardiographic left ventricular systolic assessment: side-by-side comparison with 64-slice multi-detector cardiac computed tomography.

AIMS: To investigate by real-time 3D echocardiography (RT3DE) and cardiac computed tomography (CCT) the analysis of left ventricle ejection fraction (LVEF) and volumes. METHODS AND RESULTS: A total of 67 patients (37 males, 55 +/- 11 years) were studied prospectively by RT3DE and by 64-slice CCT. RT3DE data: LVEF ranged from 30 to 78.6% (63.1 +/- 7.33); left ventricular end-diastolic volume (LVEDV) from 44.1 to 210 (104.9 +/- 29.7) mL; left ventricular end-systolic volume (LVESV) from 11.4 to 149 ( 38.9 +/- 19.3) mL. CCT data: LVEF ranged from 28 to 86% (66 +/- 8.4); LVEDV from 51 to 212 (110.3 +/- 31.2) mL; LVESV from 7 to 152 (38.2 +/- 19.2) mL. Correlations relative to RT3DE and CCT were: LVEF (r: 0.79, P < 0.0001); LVEDV (r: 0.82, P < 0.0001); and LVESV (r: 0.91, P < 0.0001). CONCLUSION: It was observed adequate correlation between RT3DE and CCT ventricular systolic function and geometry assessment.

Reference values of tissue Doppler imaging and pulsed Doppler echocardiography for analysis of left ventricular diastolic function in healthy adults.

To determine reference values for tissue Doppler imaging (TDI) and pulsed Doppler echocardiography for left ventricular diastolic function analysis in a healthy Brazilian adult population. Observations were based on a randomly selected healthy population from the city of Vitória, Espírito Santo, Brazil. Healthy volunteers (n = 275, 61.7% women) without prior histories of cardiovascular disease underwent transthoracic echocardiography. We analyzed 175 individuals by TDI and evaluated mitral annulus E'- and A'-waves from the septum (S) and lateral wall (L) to calculate E'/A' ratios. Using pulsed Doppler echocardiography, we further analyzed the mitral E- and A-waves, E/A ratios, isovolumetric relaxation times (IRTs), and deceleration times (DTs) of 275 individuals. Pulsed Doppler mitral inflow mean values for men were as follows: E-wave: 71 ± 16 cm/sec, A-wave: 68 ± 15 cm/sec, IRT: 74.8 ± 9.2 ms, DT: 206 ± 32.3 ms, E/A ratio: 1.1 ± 0.3. Pulsed Doppler mitral inflow mean values for women were as follows: E-wave: 76 ± 17, A-wave: 69 ± 14 cm/sec, IRT: 71.2 ± 10.5 ms, DT: 197 ± 33.3 ms, E/A ratio: 1.1 ± 0.3. IRT and DT values were higher in men than in women (P = 0.04 and P = 0.007, respectively). TDI values in men were as follows: E'S: 11± 3 cm/sec, A'S: 13 ± 2 cm/sec, E'S/A'S: 0.89 ± 0.2, E'L: 14 ± 3 cm/sec, A'L: 14 ± 2 cm/sec, E'L/A'L: 1.1± 0.4. E-wave/ E'S ratio: 6.9 ± 2.2; E-wave / E'L ratio: 4.9 ± 1.7. In this study, we determined pulsed Doppler and TDI derived parameters for left ventricular diastolic function in a large sample of healthy Brazilian adults.

Analysis of left ventricular regional dyssynchrony: comparison between real time 3D echocardiography and tissue Doppler imaging.

BACKGROUND: There is a paucity of information concerning left ventricular (LV) dyssynchrony assessment by real time three-dimensional (3D) echocardiography (RT3DE) versus tissue Doppler imaging (TDI). AIMS: To compare RT3DE and TDI LV dyssynchrony assessment. METHODS: A prospective study of 92 individuals (56 men, age 47 +/- 10 years), 32 with dilated cardiomyopathy (CMP), and 60 healthy individuals. By RT3DE, we measured the LV% dyssynchrony index (DI) of 6, 12, and 16 segments (SDI). By pulsed-wave TDI, we measured the QS electromechanical interval in the basal segments of the mitral valve annulus of the septum, the lateral, anterior and inferior walls, and the TDI% DI. RESULTS: In the normal group, the 3D DI was 1.1 +/- 0.8%, 1.4 +/- 1.3%, 1.8 +/- 1.7%, for 6 segments, 12 segments, and SDI, respectively. The correlation coefficient (Pearson's r) for the TDI DI and SDI was r = 0.2381 (P = 0.0470). In CMP group, the 3D DI was 4.6 +/- 5.4%, 7.9 +/- 7.1%, 11.1 +/- 7.1%, for 6 segments, 12 segments, and SDI, respectively. The correlation coefficient for TDI DI and SDI was r = 0.7838 (P < 0.0001). CONCLUSIONS: We observed a good correlation between RT3DE and tissue Doppler LV dyssynchrony assessment in patients with advanced heart failure.

Myocardial Fibrosis in Classical Low-Flow, Low-Gradient Aortic Stenosis.

Background Few data exist on the degree of interstitial myocardial fibrosis in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS) and its association with left ventricular flow reserve (FR) on dobutamine stress echocardiography. This study sought to evaluate the diffuse interstitial fibrosis measured by T1 mapping cardiac magnetic resonance technique in LFLG-AS patients with and without FR. Methods Prospective study including 65 consecutive patients (41 LFLG-AS [mean age, 67.1±8.4 years; 83% men] and 24 high-gradient aortic stenosis used as controls) undergoing dobutamine stress echocardiography to assess FR and cardiac magnetic resonance to determine the extracellular volume (ECV) fraction of the myocardium, indexed ECV (iECV) to body surface area and late gadolinium enhancement. Results Interstitial myocardial fibrosis measured by iECV was higher in patients with LFLG-AS with and without FR as compared with high-gradient aortic stenosis (35.25±9.75 versus 32.93±11.00 versus 21.19±6.47 mL/m2, respectively; P<0.001). However, both ECV and iECV levels were similar between LFLG-AS patients with and without FR ( P=0.950 and P=0.701, respectively). Also, FR did not correlate significantly with ECV (r=-0.16, P=0.31) or iECV (r=0.11, P=0.51). Late gadolinium enhancement mass was also similar in patients with versus without FR but lower in high-gradient aortic stenosis (13.3±10.2 versus 10.5±7.5 versus 4.8±5.9 g, respectively; P=0.018). Conclusions Patients with LFLG-AS have higher ECV, iECV, and late gadolinium enhancement mass compared with high-gradient aortic stenosis. Moreover, among patients with LFLG-AS, the degree of myocardial fibrosis was similar in patients with versus those without FR. These findings suggest that diffuse myocardial fibrosis may not be the main factor responsible for the absence of FR in LFLG-AS patients.

Cardiac sympathetic activity pre and post resynchronization therapy evaluated by 123I-MIBG myocardial scintigraphy.

BACKGROUND: Imaging with (123)I-metaiodobenzylguanidine (MIBG) is used for the assessment of cardiac sympathetic activity (CSA). We analyzed CSA before and after cardiac resynchronization therapy (CRT), and correlated these data with CRT response. METHODS AND RESULTS: Thirty patients with chronic heart failure and classic indications for CRT were prospectively studied before and at least 3 months after CRT. The variables analyzed were: QRS width, left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic diameter (LVEDD), heart/mediastinum MIBG uptake ratio (H/M), and washout rate (WR). After CRT, patients were divided into two groups: group 1 (21 patients), responders improving to functional class (FC) I or II; and group 2 (9 patients), nonresponders remaining in FC III or IV. After CRT, only group 1 showed favorable changes in QRS width (P =.003), LVEF (P =.01), LVEDD (P =.04), and H/M ratio (P =.003). The H/M ratio and WR were associated with CRT response (P =.005 and P =.04, respectively). The H/M ratio was the only independent predictor of CRT response (P =.01). Receiver operating characteristic curves showed that the optimal H/M ratio cutoff point was 1.36 (sensitivity, 75%; specificity, 71%). CONCLUSIONS: Improvement in CSA correlated with a positive CRT response. Lower MIBG uptake before therapy was associated with CRT nonresponse. The H/M ratio could be helpful in selecting patients for CRT.

Cardiopulmonary exercise test in patients with refractory angina: functional and ischemic evaluation

Abstract Objectives Refractory angina (RA) is a chronic condition clinically characterized by low effort tolerance; therefore, physical stress testing is not usually requested for these patients. Cardiopulmonary exercise testing (CPET) is considered a gold standard examination for functional capacity evaluation, even in submaximal tests, and it has gained great prominence in detecting ischemia. The authors aimed to determine cardiorespiratory capacity by using the oxygen consumption efficiency slope (OUES) in patients with refractory angina. The authors also studied the O2 pulse response by CPET and the association of ischemic changes with contractile modifications by exercise stress echocardiography (ESE). Methods Thirty-one patients of both sexes, aged 45 to 75 years, with symptomatic (Canadian Cardiovascular Society class II to IV) angina who underwent CPET on a treadmill and exercise stress echocardiography on a lower limb cycle ergometer were studied. ClinicalTrials.gov: NCT03218891. Results The patients had low cardiorespiratory capacity (OUES of 1.74 ± 0.4 L/min; 63.9±14.7% of predicted), and 77% of patients had a flattening or drop in O2 pulse response. There was a direct association between Heart Rate (HR) at the onset of myocardial ischemia detected by ESE and HR at the onset of flattening or drop in oxygen pulse response detected by CPET (R = 0.48; p = 0.019). Conclusion Patients with refractory angina demonstrate low cardiorespiratory capacity. CPET shows good sensitivity for detecting abnormal cardiovascular response in these patients with a significant relationship between flattening O2 pulse response during CEPT and contractile alterations detected by exercise stress echocardiography. Highlights OUES analysis is useful for assessing functional capacity in refractory angina. O2 pulse curve is correlated with contractile alterations in exercise echocardiogram. Cardiopulmonary exercise test is useful toll in patients with refractory angina.

Treatment of acromegaly improves myocardial abnormalities.

BACKGROUND: Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. METHODS: In 15 patients with active acromegaly (age range, 33.4 +/- 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 +/- 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. RESULTS: Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 +/- 21 g/m(2) x 87 +/- 21 g/m(2); P <.01), LV relative wall thickness (0.40 +/- 0.06 x 0.35 +/- 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 +/- 0.33 x 1.49 +/- 0.34; P <.001), and isovolumetric relaxation period (126 +/- 18 ms x 113 +/- 13 ms; P <.05). CONCLUSION: Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible.

Effects of growth hormone replacement therapy on metabolic and cardiac parameters, in adult patients with childhood-onset growth hormone deficiency.

OBJECTIVE: We evaluated metabolic and cardiac parameter changes with GH-therapy. DESIGN: Sixteen adults with childhood-onset hypopituitarism receiving pituitary hormone replacement, except GH-replacement, were assessed at baseline and after 6 and 12 months of GH-replacement. Sixteen healthy adults matched for sex, age, weight, height, body mass index, and body surface area served as the control group to compare cardiac function in both groups. RESULTS: All patients had GH-deficiency. After 12 months, serum insulin-like growth factor-1 levels normalized. Basal glucose or insulin levels had no alterations. The low/high density lipoprotein-cholesterol ratio decreased (3.18+/-1.32 x 2.17+/-0.8, p<0.001). Percent lean body mass increased (69.9+/-5.5 x 78.4+/-8.1%), and percent fat body mass decreased (30.1+/-5.5 x 21.6+/-8.1%) (both, p<0.001). Before treatment, patients had decreased left ventricular (LV) echocardiographic morphologic indexes, which were corrected (initial versus 12 months): interventricular septal thickness (0.68+/-0.06 x 0.78+/-0.06 cm), LV posterior wall thickness (0.69+/-0.07 x 0.78+/-0.05 cm), and LV mass index (58.9+/-11.0 x 71.1+/-9.4 g/m(2)) (all, p<0.001). Exercise capacity improved, as assessed by oxygen consumption (7.84+/-1.44 x 9.67+/-1.74 METS, p<0.001). CONCLUSIONS: GH-replacement seems to reduce cardiovascular risks in adults with childhood-onset GH-deficiency.

Posterior mitral leaflet repair with a simple segmental annulus support: the 'double-Teflon technique'.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to present immediate and late results of a modified technique for mitral valve repair--the 'double-Teflon technique'. This consists of quadrangular resection of the posterior leaflet, annulus plication with 'pledgetted' stitches over a Teflon patch, and leaflet suture. METHODS: Seventy-two patients (41 males, 31 females; mean age 60.5+/-11.9 years) with mitral insufficiency due to myxomatous degeneration and ruptured or elongated chordae tendineae underwent mitral valve repair with this technique. Fifteen patients (18%) had associated cardiovascular disease including coronary artery disease, aortic insufficiency, aortic stenosis and atrial septal defect. Operative, immediate postoperative and late operative echocardiographic data of the first 29 patients were analyzed. Actuarial survival was assessed using the Kaplan-Meier method. RESULTS: There was one operative death (1%). By the late postoperative period, 95% of survivors were in NYHA functional class I. There were no episodes of hemolysis or endocarditis; the linearized rate for thromboembolism was 1.4%/patient-year. Actuarial survival at 72 months was 94.5+/-3.2%. Doppler echocardiography showed a significant decrease in mean left atrial diameter (p = 0.0001) and left ventricular diastolic diameter (p = 0.0003). CONCLUSION: Mitral valve repair with the 'double-Teflon technique' is associated with low operative mortality, satisfactory survival rates, and good clinical outcome.