Diastolic ventricular interactions in endurance-trained athletes during orthostatic stress

Enhanced left-ventricular (LV) compliance is a common adaptation to endurance training. This adaptation may have differential effects under conditions of altered venous return. The purpose of this investigation was to assess the effect of cardiac (un)loading on right ventricular (RV) cavity dimensions and LV volumes in endurance-trained athletes and normally active males. Eight endurance-trained (Vo(2max), 65.4 +/- 5.7 ml.kg(-1).min(-1)) and eight normally active (Vo(2max), 45.1 +/- 6.0 ml.kg(-1).min(-1)) males underwent assessments of the following: 1) Vo(2max), 2) orthostatic tolerance, and 3) cardiac responses to lower-body positive (0-60 mmHg) and negative (0 to -80 mmHg) pressures with echocardiography. In response to negative pressures, echocardiographic analysis revealed a similar decrease in RV end-diastolic cavity area in both groups (e.g., at -80 mmHg: normals, 21.4%; athletes, 20.8%) but a greater decrease in LV end-diastolic volume in endurance-trained athletes (e.g., at -80 mmHg: normals, 32.3%; athletes, 44.4%; P < 0.05). Endurance-trained athletes also had significantly greater decreases in LV stroke volume during lower-body negative pressure. During positive pressures, endurance-trained athletes showed larger increases in LV end-diastolic volume (e.g., at +60 mmHg; normals, 14.1%; athletes, 26.8%) and LV stroke volume, despite similar responses in RV end-diastolic cavity area (e.g., at +60 mmHg: normals, 18.2%; athletes, 24.2%; P < 0.05). This investigation revealed that in response to cardiac (un)loading similar changes in RV cavity area occur in endurance-trained and normally active individuals despite a differential response in the left ventricle. These differences may be the result of alterations in RV influence on the left ventricle and/or intrinsic ventricular compliance.     

Nocturnal Blood Pressure Pattern Affects Left Ventricular Remodeling and Late Gadolinium Enhancement in Patients with Hypertension and Left Ventricular Hypertrophy

Background

Left ventricular hypertrophy (LVH) is an independent predictor of cardiac mortality, regardless of its etiology. Previous studies have shown that high nocturnal blood pressure (BP) affects LV geometry in hypertensive patients. It has been suggested that continuous pressure overload affects the development of LVH, but it is unknown whether persistent pressure influences myocardial fibrosis or whether the etiology of LVH is associated with myocardial fibrosis. Comprehensive cardiac magnetic resonance (CMR) including the late gadolinium enhancement (LGE) technique can evaluate both the severity of changes in LV geometry and myocardial fibrosis. We tested the hypothesis that the nocturnal non-dipper BP pattern causes LV remodeling and fibrosis in patients with hypertension and LVH.

Methods

Forty-seven hypertensive patients with LVH evaluated by echocardiography (29 men, age 73.0±10.4 years) were examined by comprehensive CMR and 24-h ambulatory blood pressure monitoring (ABPM).

Results and Conclusions

Among the 47 patients, twenty-four had nocturnal non-dipper BP patterns. Patients with nocturnal non-dipper BP patterns had larger LV masses and scar volumes independent of etiologies than those in patients with dipper BP patterns (p = 0.035 and p = 0.015, respectively). There was no significant difference in mean 24-h systolic BP between patients with and without nocturnal dipper BP patterns (p = 0.367). Among hypertensive patients with LVH, the nocturnal non-dipper blood pressure pattern is associated with both LV remodeling and myocardial fibrosis independent of LVH etiology.     

Pulmonary function in young and older athletes and untrained men

This study compared the lung volumes and pulmonary functions of older endurance-trained athletes with those of healthy sedentary age-matched controls, young athletes, and young untrained men to determine whether training affects the age-associated changes in these variables. Despite large differences in maximal 02 consumption (VO2max), the older athletes and their sedentary peers had similar values for all pulmonary variables when expressed as absolute values. However, because the older athletes were shorter than the older sedentary men, their vital capacity, total lung capacity (TLC), and forced expiratory volume in 1 s were significantly larger than those of the older sedentary men when normalized for age and height; the average values for maximal voluntary ventilation and residual volume (RV) were also larger in the older athletes when normalized for age and height, but the differences were not significant. The young trained and untrained men did not differ in any of these measures. TLC was the only pulmonary variable that was the same in the young and older men; RV and the RV-to-TLC ratio were larger, whereas all other pulmonary function and volume measures were lower in the older men compared with the younger men. The older athletes were the only group whose lung volumes and pulmonary function measures were all, except for RV, substantially greater than expected based on their age and height. Thus prolonged strenuous endurance training in these older highly trained endurance athletes appears to have altered the decline in pulmonary function and volumes associated with aging.     

Cardiac atrophy in women following bed rest.

Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 +/- 6 to 84 +/- 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P < 0.001) and RV masses (0.7 +/- 0.1 to 0.8 +/- 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 +/- 2 to 11 +/- 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 +/- 14 to 80 +/- 16 ml; P = 0.02) and major-axis length (91 +/- 5 to 88 +/- 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 +/- 0.2 kg control; 3.1 +/- 0.04 kg exercise; 2.8 +/- 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.     

Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy

Background

Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM.

Methods

Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis.

Results

LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6–2340.8] vs. 866.6 [707.2–1875.2] pmol/L, P = 0.003; 0.024 [0.010–0.049] vs. 0.010 [0.005–0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%.

Conclusions

Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.     

Prognostic value of the ABCD2 score beyond short-term follow-up after transient ischemic attack (TIA) - a cohort study

Background

In patients with Duchenne Muscular Dystrophy (DMD), the absent or diminished dystrophin leads to progressive skeletal muscle and heart failure. We evaluated the role of myocardial inflammation as a precipitating factor in the development of heart failure in DMD.

Methods

20 DMD patients (aged 15-18 yrs) and 20 age-matched healthy volunteers were studied and followed-up for 2 years. Evaluation of myocarditis with cardiovascular magnetic resonance imaging (CMR) was performed using STIR T2-weighted (T2W), T1-weighted (T1W) before and after contrast media and late enhanced images (LGE). Left ventricular volumes and ejection fraction were also calculated. Myocardial biopsy was performed in patients with positive CMR and immunohistologic and polymerase chain reaction (PCR) analysis was employed.

Results

In DMD patients, left ventricular end-diastolic volume (LVEDV) was not different compared to controls. Left ventricular end-systolic volume (LVESV) was higher (45.1 ± 6.6 vs. 37.3 ± 3.8 ml, p < 0.001) and left ventricular ejection fraction (LVEF) was lower (53.9 ± 2.1 vs. 63 ± 2.4%, p < 0.001). T2 heart/skeletal muscle ratio and early T1 ratio values in DMD patients presented no difference compared to controls. LGE areas were identified in six DMD patients. In four of them with CMR evidence of myocarditis, myocardial biopsy was performed. Active myocarditis was identified in one and healing myocarditis in three using immunohistology. All six patients with CMR evidence of myocarditis had a rapid deterioration of left ventricular function during the next year.

Conclusions

DMD patients with myocardial inflammation documented by CMR had a rigorous progression to heart failure.     

Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction

Background

We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI).

Methods

Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured.

Results

Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r?=?-0.57, p?<?0.001), regional wall motion score index (r?=?0.52, p?=?0.001), and global longitudinal strain (r?=?0.56, p?<?0.001). The diastolic functional indices significantly correlated with age (r?=?-0.64, p?<?0.001), LV twist (r?=?-0.39, p?=?0.02), average non-infarcted myocardial circumferential strain (r?=?-0.52, p?=?0.001), and LV end-diastolic wall stress index (r?=?-0.47, p?=?0.003 with e’) but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury.

Conclusions

In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function.     

Paradoxical Interventricular Septal Motion as a Major Determinant of Late Gadolinium Enhancement in Ventricular Insertion Points in Pulmonary Hypertension

Background

This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH).

Methods

Forty-six consecutive PH patients (mean pulmonary artery pressure ≥25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index.

Results

Mean pulmonary arterial pressure (MPAP) of PH patients was 38±9 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47–2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = −0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001).

Conclusions

LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.     

In vivo MRI characterization of progressive cardiac dysfunction in the mdx mouse model of muscular dystrophy

Aims

The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice.

Methods and Results

Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy.

Conclusions

MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases.     

Assessing functional mitral regurgitation with exercise echocardiography: rationale and clinical applications

Background

Strain, and particularly Longitudinal Peak Systolic Strain (LPSS), plays a role in investigating the segmental and overall contractility of the heart which is a particularly interesting feature in athletes in whom regular training determines several morphological and functional modifications in both the ventricles, that normally work at different loads. Speckle tracking techniques assess the LPSS of LV and RV from B-mode imaging in real time, with uniform accuracy in all segments, and can verify the possible dissimilar segmental contributions of the two chambers to overall myocardial contraction. The aim of the study is to quantify the LPSS in real time in both the ventricles in order to estimate any possible different deformation properties in them during a systolic period.

Methods

32 subjects (20 athletes and 18 controls) were submitted to a standard echocardiographic examination at rest and after a Hand Grip (HG) stress. From a four-chamber-view image, the LPSS parameter was measured with Speckle Tracking analysis in the basal and medium-apical segments of the two ventricles, at rest and after HG.

Results

In both athletes and controls, LPSS values were significantly higher in the RV of athletes (RV LPSS^{medium-apical} -23.87 ± 4.94;^{basalfreewall} -25.04 ± 4.12 at rest) and controls (RV LPSS^{medium-apical} -25.21 ± 4.97;^{basalfreewall} -28.69 ± 4.62 at rest) than in the LV of both (athletes LV LPSS^{medium-apical} -18.14 ± 4.16;^{basallateralwall} -16.05 ± 12.32; controls^{medium-apical} -18.81 ± 2.64;^{basallateralwall} -19.74 ± 3.84) With the HG test a significant enhancement of the LPSS(with P <.05) in the medium-apical segments of LV and RV was evident, but only in athletes; there was no modification of the standard echo-parameters in either group.

Conclusion

ST analysis is an easy method for investigating the contractility of the RV through deformation parameters, showing greater involvement of the RV than LV at rest. In athletes only, after isometric stress the two ventricles show particular myocardial deformation properties of the regions around the apex where the curvature of the wall is more marked. The clinical application of this new approach in athletes and normal subjects requires further investigation.     

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output (r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes (P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.     

Myocardial performance index in female athletes

Background

Long-term intensive training leads to morphological and mechanical changes in the heart generally known as “athlete’s heart”. Previous studies have suggested that the diastolic and systolic function of the ventricles is unaltered in athletes compared to sedentary.The purpose of this study was to investigate myocardial performance index (MPI) by pulsed wave Doppler (PWD) and by tissue Doppler imaging (TDI) in female elite athletes compared to sedentary controls.

Methods

The study consisted of 32 athletes (mean age 20 ± 2 years) and 34 sedentary controls (mean age 23 ± 2 years). MPI by PWD and TDI were measured in the left (LV) and right ventricle (RV) in both groups. Moreover, comparisons of MPI by the two methods and between the LV and RV within the two groups were made.

Results

There were no significant differences in MPI between athletes and controls (p > 0.05), whereas the LV had significantly higher MPI compared to RV (p < 0.001, in athletes and controls). The agreement and the correlation between the two methods measuring MPI showed low agreement and no correlation (athletes RV r = ?0.027, LV r = 0.12; controls RV r = 0.20, LV r = 0.30).

Conclusion

The global function of the LV and RV measured by MPI with PWD and TDI is similar in female athletes compared to sedentary controls. Conversely, both MPI by PWD and by TDI shows a significant difference between the LV and RV. However, the agreement and correlation between conventional methods of measuring MPI by PWD compared to MPI by TDI is very poor in both these populations.

     

Chronic fatigue syndrome in women assessed with combined cardiac magnetic resonance imaging

Objective

In chronic fatigue syndrome (CFS), only a few imaging and histopathological studies have previously assessed either cardiac dimensions/function or myocardial tissue, suggesting smaller left ventricular (LV) dimensions, LV wall motion abnormalities and occasionally viral persistence that may lead to cardiomyopathy. The present study with cardiac magnetic resonance (CMR) imaging is the first to use a contrast-enhanced approach to assess cardiac involvement, including tissue characterisation of the LV wall.

Methods

CMR measurements of 12 female CFS patients were compared with data of 36 age-matched, healthy female controls. With cine imaging, LV volumes, ejection fraction (EF), mass, and wall motion abnormalities were assessed. T2-weighted images were analysed for increased signal intensity, reflecting oedema (i.?e. inflammation). In addition, the presence of contrast enhancement, reflecting fibrosis (i.?e. myocardial damage), was analysed.

Results

When comparing CFS patients and healthy controls, LVEF (57.9 ± 4.3?% vs. 63.7 ± 3.7?%; p < 0.01), end-diastolic diameter (44 ± 3.7 mm vs. 49 ± 3.7 mm; p < 0.01), as well as body surface area corrected LV end-diastolic volume (77.5 ± 6.2 ml/m² vs. 86.0 ± 9.3 ml/m²; p < 0.01), stroke volume (44.9 ± 4.5 ml/m² vs. 54.9 ± 6.3 ml/m²; p < 0.001), and mass (39.8 ± 6.5 g/m² vs. 49.6 ± 7.1 g/m²; p = 0.02) were significantly lower in patients. Wall motion abnormalities were observed in four patients and contrast enhancement (fibrosis) in three; none of the controls showed wall motion abnormalities or contrast enhancement. None of the patients or controls showed increased signal intensity on the T2-weighted images.

Conclusion

In patients with CFS, CMR demonstrated lower LV dimensions and a mildly reduced LV function. The presence of myocardial fibrosis in some CFS patients suggests that CMR assessment of cardiac involvement is warranted as part of the scientific exploration, which may imply serial non-invasive examinations.

     

Cardiovascular response to acute hypoxemia induced by prolonged breath holding in air

Prolonged breath hold (BH) represents a valid model for studying the cardiac adaptation to acute hypoxemia in humans. Cardiac magnetic resonance (CMR) allows a three-dimensional, high-resolution, noninvasive, and nonionizing anatomical and functional evaluation of the heart. The aim of the study was to assess the adaptation of the cardiovascular system to prolonged BH in air. Ten male volunteer diving athletes (age 30 +/- 6 yr) were studied during maximal BH duration with CMR. Four epochs were studied: I, rest; II and III, intermediate BH; and IV, peak BH. Oxygen saturation (So(2)), heart rate (HR), blood pressure (BP), systemic vascular resistance (VR), end-diastolic (EDV) and end-systolic volumes (ESV), stroke volume (SV), cardiac output (CO), ejection fraction (EF), maximal elastance index (EL), systolic wall thickening (SWT), and end-systolic wall stress (ESWS) of the left ventricle (LV) were measured in all four BH epochs. Average BH duration was 3.7 +/- 0.3 min. So(2) was reduced (I: 97 +/- 0.2%, range 96-98%, vs. IV: 84 +/- 2.0%, range 76-92%; P < 0.00001). BP, EDV, ESV, SV, CO, and ESWS linearly increased from epochs I to IV, whereas EF, EL, and SWT showed an opposite behavior, decreasing from resting to epoch IV (all trends are P < 0.01). During prolonged BH in air, a marked enlargement of the LV chamber occurs in healthy diving athletes. This response to acute hypoxemia allows SV,CO, and arterial pressure to be maintained despite the severe reduction in LV contractile function.     

Combined pulmonary stenosis and insufficiency preserves myocardial contractility in the developing heart of growing swine at midterm follow-up.

This study was conducted to determine the effects of chronic combined pulmonary stenosis and pulmonary insufficiency (PSPI) on right (RV) and left ventricular (LV) function in young, growing swine. Six pigs with combined PSPI were studied, and data were compared with previously published data of animals with isolated pulmonary insufficiency and controls. Indexes of systolic function (stroke volume, ejection fraction, and cardiac functional reserve), myocardial contractility (slope of the end-systolic pressure-volume and change in pressure over time-end-diastolic volume relationship), and diastolic compliance were assessed within 2 days of intervention and 3 mo later. Magnetic resonance imaging was used to quantify pulmonary insufficiency and ventricular volumes. The conductance catheter was used to obtain indexes of the cardiac functional reserve, diastolic compliance, and myocardial contractility from pressure-volume relations acquired at rest and under dobutamine infusion. In the PSPI group, the pulmonary regurgitant fraction was 34.3 +/- 5.8%, the pressure gradient across the site of pulmonary stenosis was 20.9 +/- 20 mmHg, and the average RV peak systolic pressure was 70% systemic at 12 wk follow-up. Biventricular resting cardiac outputs and cardiac functional reserves were significantly limited (P < 0.05), LV diastolic compliance significantly decreased (P < 0.05), but RV myocardial contractility significantly enhanced (P < 0.05) compared with control animals at 3-mo follow-up. In the young, developing heart, chronic combined PSPI impairs biventricular systolic pump function and diastolic compliance but preserves RV myocardial contractility.     

Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study

Background and Aims

Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.

Methods and Results

Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9–1.3) mg/dL, and 5.8 (5.4–7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250–355) vs 581 (437–698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.

Conclusions

Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time.     

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops.     

Left ventricular systolic torsion correlates global cardiac performance during dyssynchrony and cardiac resynchronization therapy

Left ventricular (LV) systolic torsion is a primary mechanism contributing to stroke volume (SV). We hypothesized that change in LV torsion parallels changes in global systolic performance during dyssynchrony and cardiac resynchronization therapy (CRT). Seven anesthetized open chest dogs had LV pressure-volume relationship. Apical, basal, and mid-LV cross-sectional echocardiographic images were studied by speckle tracking analysis. Right atrial (RA) pacing served as control. Right ventricular (RV) pacing simulated left bundle branch block. Simultaneous RV-LV free wall and RV-LV apex pacing (CRTfw and CRTa, respectively) modeled CRT. Dyssynchrony was defined as the time difference in peak strain between earliest and latest segments. Torsion was calculated as the maximum difference between the apical and basal rotation. RA pacing had minimal dyssynchrony (52 ± 36 ms). RV pacing induced dyssynchrony (189 ± 61 ms, P < 0.05). CRTa decreased dyssynchrony (46 ± 36 ms, P < 0.05 vs. RV pacing), whereas CRTfw did not (110 ± 96 ms). Torsion during baseline RA was 6.6 ± 3.7°. RV pacing decreased torsion (5.1 ± 3.6°, P < 0.05 vs. control), and reduced SV, stroke work (SW), and dP/dt(max) compared with RA (21 ± 5 vs. 17 ± 5 ml, 252 ± 61 vs. 151 ± 64 mJ, and 2,063 ± 456 vs. 1,603 ± 424 mmHg/s, respectively, P < 0.05). CRTa improved torsion, SV, SW, and dP/dt(max) compared with RV pacing (7.7 ± 4.7°, 23 ± 3 ml, 240 ± 50 mJ, and 1,947 ± 647 mmHg/s, respectively, P < 0.05), whereas CRTfw did not (5.1 ± 3.6°, 18 ± 5 ml, 175 ± 48 mJ, and 1,699 ± 432 mmHg/s, respectively, P < 0.05). LV torsion changes covaried across conditions with SW (y = 0.94x+12.27, r = 0.81, P < 0.0001) and SV (y = 0.66x+0.91, r = 0.81, P < 0.0001). LV dyssynchrony changes did not correlate with SW or SV (r = -0.12, P = 0.61 and r = 0.08, P = 0.73, respectively). Thus, we conclude that LV torsion is primarily altered by dyssynchrony, and CRT that restores LV performance also restores torsion.     

SPARC mediates early extracellular matrix remodeling following myocardial infarction

Secreted protein, acidic, and rich in cysteine (SPARC) is a matricellular protein that functions in the extracellular processing of newly synthesized collagen. Collagen deposition to form a scar is a key event following a myocardial infarction (MI). Because the roles of SPARC in the early post-MI setting have not been defined, we examined age-matched wild-type (WT; n=22) and SPARC-deficient (null; n=25) mice at day 3 post-MI. Day 0 WT (n=28) and null (n=20) mice served as controls. Infarct size was 52 ± 2% for WT and 47 ± 2% for SPARC null (P=NS), indicating that the MI injury was comparable in the two groups. By echocardiography, WT mice increased end-diastolic volumes from 45 ± 2 to 83 ± 5 μl (P < 0.05). SPARC null mice also increased end-diastolic volumes but to a lesser extent than WT (39 ± 3 to 63 ± 5 μl; P < 0.05 vs. day 0 controls and vs. WT day 3 MI). Ejection fraction fell post-MI in WT mice from 57 ± 2 to 19 ± 1%. The decrease in ejection fraction was attenuated in the absence of SPARC (65 ± 2 to 28 ± 2%). Fibroblasts isolated from SPARC null left ventricle (LV) showed differences in the expression of 22 genes encoding extracellular matrix and adhesion molecule genes, including fibronectin, connective tissue growth factor (CTGF; CCN2), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-2 (TIMP-2). The change in fibroblast gene expression levels was mirrored in tissue protein extracts for fibronectin, CTGF, and MMP-3 but not TIMP-2. Combined, the results of this study indicate that SPARC deletion preserves LV function at day 3 post-MI but may be detrimental for the long-term response due to impaired fibroblast activation.     

Training-specific changes in cardiac structure and function: a prospective and longitudinal assessment of competitive athletes.

This prospective, longitudinal study examined the effects of participation in team-based exercise training on cardiac structure and function. Competitive endurance athletes (EA, n = 40) and strength athletes (SA, n = 24) were studied with echocardiography at baseline and after 90 days of team training. Left ventricular (LV) mass increased by 11% in EA (116 +/- 18 vs. 130 +/- 19 g/m(2); P < 0.001) and by 12% in SA (115 +/- 14 vs. 132 +/- 11 g/m(2); P < 0.001; P value for the compared Delta = NS). EA experienced LV dilation (end-diastolic volume: 66.6 +/- 10.0 vs. 74.7 +/- 9.8 ml/m(2), Delta = 8.0 +/- 4.2 ml/m(2); P < 0.001), enhanced diastolic function (lateral E': 10.9 +/- 0.8 vs. 12.4 +/- 0.9 cm/s, P < 0.001), and biatrial enlargement, while SA experience LV hypertrophy (posterior wall: 4.5 +/- 0.5 vs. 5.2 +/- 0.5 mm/m(2), P < 0.001) and diminished diastolic function (E' basal lateral LV: 11.6 +/- 1.3 vs. 10.2 +/- 1.4 cm/s, P < 0.001). Further, EA experienced right ventricular (RV) dilation (end-diastolic area: 1,460 +/- 220 vs. 1,650 +/- 200 mm/m(2), P < 0.001) coupled with enhanced systolic and diastolic function (E' basal RV: 10.3 +/- 1.5 vs. 11.4 +/- 1.7 cm/s, P < 0.001), while SA had no change in RV parameters. We conclude that participation in 90 days of competitive athletics produces significant training-specific changes in cardiac structure and function. EA develop biventricular dilation with enhanced diastolic function, while SA develop isolated, concentric left ventricular hypertrophy with diminished diastolic relaxation.