Evaluation of the right ventricle: Comparison of gated blood-pool single photon electron computed tomography and echocardiography with cardiac magnetic resonance

Background

The evaluation of the right ventricle (RV) is a challenge; as a result six transthoracic echocardiography (TTE) parameters have been suggested. While gated blood-pool single photon electron computed tomography (GBPS) is a promising technique, there is currently no completely automated and validated processing software available clinically. Consequently, cardiac magnetic resonance (CMR) imaging remains the gold standard for RV assessment. We aimed to compare RV evaluation by GBPS and TTE to CMR.

Methods

Fifty-eight patients underwent CMR, GBPS and TTE for RV assessment, including volumes, RVEF and TTE's indices of RV function (fractional area change (FAC), RV myocardial performance index by pulsed wave Doppler (MPI-PWD) and tissue Doppler (MPI-TDI) and tricuspid annular plane systolic excursion (TAPSE) by M-Mode and tissue Doppler (TAPSE-TDI)). GBPS was performed using both a commercial (QBS) and the Montreal Heart Institute (MHI) proprietary software.

Results

Nuclear medicine derived volumes quantification showed very good correlations with CMR, for RV end-diastolic (r = 0.84 and 0.77, all p < 0.001) and end-systolic (r = 0.82 and 0.67, all p < 0.001) volumes by MHI and QBS software respectively. RVEF showed a significant correlation with CMR in patients with RVEF ≤ 45% (r = 0.54, p = 0.029 and r = 0.55, p = 0.028, by MHI and QBS respectively). Among TTE parameters, only FAC and MPI-TDI were significantly correlated with CMR-RVEF, mainly for RVEF ≤ 45% (r = 0.63, p = 0.011 and r = 0.58, p = 0.046).

Conclusions

GBPS, both with MHI and QBS software, exhibited significant correlations with CMR for evaluation of the RV (volumes and decreased RVEF estimation). Among TTE's parameters, only FAC and MPI-TDI showed significant correlation with CMR with RVEF ≤ 45%.     

Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system

Objectives

To assess ventricular dysfunction and ventricular interaction after repair of Tetralogy of Fallot (ToF) employing echocardiography speckle-tracking and cardiac magnetic resonance imaging (CMR).

Background

Severe pulmonary regurgitation and right ventricular (RV) dysfunction are common after repair of ToF and may also affect the shape and function of the left ventricle (LV). Recent studies suggest that LV dysfunction may be of particular prognostic value.

Methods and results

Twenty-one consecutive adults with repaired ToF (15 male, mean age 38 ± 11 years, 7 with severe PR) underwent a comprehensive echocardiographic exam including speckle-tracking analysis, CMR and cardiopulmonary exercise testing. Twenty-one subjects without relevant heart disease served as controls. Echocardiographically measured RV diameters correlated with RV volumes obtained from CMR (r = 0.63; p = 0.006). In addition, a close correlation was found between RV and LV function on CMR (r = 0.74, p = 0.002), speckle-tracking LV and RV peak longitudinal 2D strain (r = 0.66, p = 0.003) and mitral and tricuspid annular plain systolic excursion (r = 0.71, p = 0.0003). While LV ejection fraction was normal in the majority of patients and not different from controls, LV longitudinal strain was significantly reduced in ToF patients (− 16.5 ± 3.3 vs. -20.5 ± 2.7%, p = 0.0001).

Conclusion

Left and right ventricular function both by CMR and speckle-tracking is interrelated in adults with repaired ToF. Despite normal LV ejection fraction, 2D longitudinal strain is significantly reduced in ToF patients, suggesting subclinical LV myocardial damage. Considering the potential prognostic value of LV dysfunction in ToF, this measurement may gain importance and should be included in future outcome studies.     

Assessment of right ventricular systolic function: Comparison between cardiac magnetic resonance derived ejection fraction and pulsed-wave tissue Doppler imaging of the tricuspid annulus

Background

Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Its practical determination by echocardiography remains challenging. We compared routine assessment of lateral tricuspid annular systolic motion velocity (TV_lat, cm/s) using pulsed-wave tissue Doppler imaging from the apical 4-chamber view with cardiac magnetic resonance (CMR) as reference method.

Methods and results

254 individuals (43 ± 18 years) underwent both CMR (contiguous short axis slices; retrogated cine steady state free precession technique; manual contour tracing) and echocardiography within 2 ± 2 months. Seventy-five had coronary artery disease, 87 congenital heart disease, 17 dilated cardiomyopathy, 15 pulmonary artery hypertension, and 47 normal findings. RV ejection fraction (EF) by CMR was 51 ± 12% (range 17-78%). There was a linear correlation between RVEF and TV_lat (r = 0.60; p < 0.0001). A TV_lat cut-off of 12 cm/s identified patients with normal EF (≥ 50%) with 81% sensitivity and 68% specificity, and a threshold of TV_lat < 9 cm/s identified patients with severely reduced RVEF (< 30%) with 82% sensitivity and 86% specificity.

Conclusions

Systolic long-axis velocity measurements of the lateral tricuspid annulus allow a reliable assessment of RVEF in clinical routine. A threshold of TV_lat < 9 cm/s identifies patients with severely reduced RVEF (< 30%) with high sensitivity and specificity.     

Pulmonary valve replacement in chronic pulmonary regurgitation in adults with congenital heart disease: Impact of preoperative QRS-duration and NT-proBNP levels on postoperative right ventricular function

Background

Chronic severe pulmonary regurgitation (PR) causes progressive right ventricular (RV) dysfunction and heart failure. Parameters defining the optimal time point for surgery of chronic PR are lacking. The present study prospectively evaluated the impact of preoperative clinical parameters, cardiorespiratory function, QRS duration and NT-proBNP levels on post operative RV function and volumes assessed by cardiac magnetic resonance imaging (CMR) in patients with chronic severe PR undergoing pulmonary valve replacement.

Methods and results

CMR was performed pre- and 6 months postoperatively in 27 patients (23.6 ± 2.9 years, 15 women) with severe PR. Postoperatively, RV endsystolic (RVESVI) and enddiastolic volume indices (RVEDVI) decreased significantly (RVESVI pre 78.2 ± 20.4 ml/m² BSA vs. RVESVI post 52.2 ± 16.8 ml/m²BSA, p < 0.001; RVEDVI pre 150.7 ± 27.7 ml/m²BSA vs. RVEDVI post 105.7 ± 26.7 ml/m²BSA; p < 0,001). With increasing preoperative QRS-duration, postoperative RVEF decreased significantly (r =−0.57; p < 0.005). Preoperative QRS-duration smaller than the median (156 ms) predicted an improved RVEF compared to QRS-duration ≥ 156 ms (54.9% vs 46.8%, p < 0.05). Multivariate analysis identified preoperative QRS duration as an independent predictor of postoperative RVEF (p < 0.005). NT-proBNP levels correlated with changes in RVEDI (r = 0.58 p < 0,005) and RVESVI (r = 0.63; p < 0,0001). Multivariate analysis identified NT-proBNP levels prior to PVR as an independent predictor of volume changes (p < 0.05).

Conclusion

Valve replacement in severe pulmonary regurgitation causes significant reduction of RV volumes. Both, preoperative NT-proBNP level elevation and QRS prolongation indicate patients with poorer outcome regarding RV function and volumes.     

Évaluation de la fraction d’éjection ventriculaire droite par la mesure du déplacement de l’anneau tricuspide via l’utilisation du tricuspid annular displacement (TAD)

Introduction

The ultrasound assessment of RV structure and function is often sub-optimal. The range of excursions of the mitral or tricuspid annulus measured in millimetre by 2D or TM-mode in centimetre per second by DTI-mode echocardiography has been shown to reflect the systolic function of both ventricles.

Methods

We studied a new technique based on a tissue tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement (TAD) (QLAB, Philips Medical Imaging). Twenty-six patients (pts) referred for magnetic resonance imaging (MRI) and 44 control subjects underwent a complete transthoracic echocardiography. MRI of the right ventricular ejection fraction (RVEF) was correlated by linear regression with TAD. Sixteen pts (61.5%) exhibited right ventricular systolic dysfunction (MRI RVEF < 40%).

Results

The MRI RVEF was positively correlated with TAD (R² = 0,65; p < 0,0001). A value of TAD <14 mm predicted right ventricular dysfunction with a sensitivity of 87.5% and a specificity of 90%. Most of (90%) healthy subjects exhibited TAD values exceeding this cut-off point (mean: 16.9 ± 1.64 mm; range: 13.3 to 24.8 mm). Negative correlation was found between TAD and age (R² = 0,36; p < 0,0001).

Conclusion

Our study is the first to correlate TAD with MRI RVEF. TAD is a simple, rapid, and non-invasive tool for right ventricular systolic function assessment.     

Incretin secretion is not restored by short-term strict glycaemic control in Korean hyperglycaemic patients with type 2 diabetes

Aims

To determine whether short-term strict glycaemic control could restore incretin secretion in type 2 diabetic patients. The factors associated with incretin levels were also investigated.

Methods

A meal tolerance test (MTT) was performed in eighteen poorly controlled (pDM) and fifteen well controlled (wDM) diabetic patients. Fourteen patients in the pDM group underwent follow-up MTT after strict glycaemic control. The secretions of intact glucagon-like peptide-1 (iGLP-1) and total glucose-dependent insulinotropic polypeptide (tGIP) during MTT were calculated by total and incremental area under the curve (TAUC and IAUC) values.

Results

Posttreatment HbA1c level was significantly improved in the pDM group (11.2 ± 0.9 to 7.9 ± 0.9%). However, the secretion of incretin hormones was not increased in the posttreatment pDM group (TAUCiGLP-1, 3612 ± 587 to 2916 ± 405 pmol/L min; TAUCtGIP, 9417 ± 1099 to 8338 ± 903 pmol/L min). IAUCiGLP-1 was negatively correlated (r = −0.446, P = 0.011) and independently associated (β = −137.2, P = 0.027) with insulin resistance assessed by homeostasis model assessment.

Conclusions

Incretin secretion is not restored by short-term strict glycaemic control. Decreased incretin secretion seems to develop early in the course of type 2 diabetes with increasing insulin resistance, but not to be influenced by glycaemic status.     

Diastolic ventricular interaction in patients after atrial switch for transposition of the great arteries: A speckle tracking echocardiographic study

Background

We tested the hypothesis that diastolic ventricular interaction occurs after atrial switch operation for transposition of the great arteries (TGA) and that subpulmonary LV diastolic function is influenced by septal geometry.

Methods

Twenty-nine patients (male 19) after atrial switch operation for TGA aged 20.8 ± 4.1 years and 27 healthy controls were studied. Two-dimensional longitudinal systolic strain, systolic (SRs), early diastolic (SRe), and late diastolic (SRa) strain rates of both ventricles were determined using speckle tracking echocardiography. Early diastolic trans-atrioventricular velocity (E) and myocardial early diastolic myocardial velocity (e) at the ventricular free wall-annular junction were measured. Geometry of the morphologic left ventricle was quantified by the diastolic eccentricity index (EI).

Results

In both systemic and subpulmonary ventricles, SRe and SRa were significantly lower and trans-atrioventricular E/e ratios higher in patients than controls (all p < 0.001). In patients, RV SRe correlated with left ventricular (LV) SRe (r = 0.49, p = 0.008), and RV SRa correlated with LV SRa (r = 0.46, p = 0.01). Significant leftward shifting of the septum in patients was reflected by the greater LV EI (p < 0.001). In patients, LV EI correlated with age- and sex-adjusted z score of LV end-diastolic volume. As a group, LV EI correlated negatively with LV SRe (r =−0.62, p < 0.001) and LV SRa (r = − 0.51, p < 0.001), and positively with mitral E/e ratio (r = 0.33, p = 0.02).

Conclusions

Systemic RV diastolic dysfunction occurs after atrial switch operation and correlates with subpulmonary LV diastolic dysfunction. The observed diastolic ventricular interaction may potentially be mediated through alteration of septal geometry.     

Targeting dietary fat or glycemic load in the treatment of obesity and type 2 diabetes: a randomized controlled trial

Aims

To compare the effects of lifestyle modification programs that prescribe low-glycemic load (GL) vs. low-fat diets in a randomized trial.

Methods

Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction, delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity. Changes in weight, HbA_1c, and other metabolic parameters were compared at weeks 20 and 40.

Results

Weight loss did not differ between groups at week 20 (low-fat: −5.7 ± 3.7%; low-GL: −6.7 ± 4.4%, p = .26) or week 40 (low-fat: −4.5 ± 7.5%; low-GL: −6.4 ± 8.2%, p = .28). Adjusting for changes in antidiabetic medications, subjects on the low-GL diet had larger reductions in HbA_1c than those on the low-fat diet at week 20 (low-fat: −0.3 ± 0.6%; low-GL: −0.7 ± 0.6%, p = .01), and week 40 (low-fat: −0.1 ± 1.2%; low-GL: −0.8 ± 1.3%; p = .01). Groups did not differ significantly on any other metabolic outcomes (p ≥ .06).

Conclusions

Results suggest that targeting GL, rather than dietary fat, in a low-calorie diet can significantly enhance the effect of weight loss on HbA_1c in patients with type 2 diabetes.     

Mechanisms of maintained exercise capacity in adults with repaired tetralogy of Fallot

Background

The mechanisms whereby cardiac output is augmented with exercise in adult repaired tetralogy of Fallot (TOF) are poorly characterised.

Methods

16 repaired TOF patients (25 ± 7 years of age) and 8 age and sex matched controls (25 ± 4 years of age) underwent cardiopulmonary exercise testing and then real-time cardiac MRI (1.5 T) at rest and whilst exercising within the scanner, aiming for 30% heart rate reserve (Level 1) and 60% heart rate reserve (Level 2), using a custom-built MRI compatible foot pedal device.

Results

At rest, TOF patients had severely dilated RVs (indexed RV end-diastolic volume: 149 ± 37 mL/m²), moderate-severe PR (regurgitant fraction 35 ± 12%), normal RV fractional area change (FAC) (52 ± 7%) and very mildly impaired exercise capacity (83 ± 15% of predicted maximal work rate). Heart rate and RV FAC increased significantly in TOF patients (75 ± 10 vs 123 ± 17 beats per minute, p < 0.001; 44 ± 7 vs 51 ± 10%, p = 0.025), and similarly in control subjects (70 ± 11 vs 127 ± 12 beats per minute, p < 0.001; 49 ± 7 vs 61 ± 9%, p = 0.003), when rest was compared to Level 2. PR fraction decreased significantly but only modestly, from rest to Level 2 in TOF patients (37 ± 15 to 31 ± 15%, p = 0.002). Pulmonary artery net forward flow was maintained and did not significantly increase from rest to Level 2 in TOF patients (70 ± 19 vs 69 ± 12 mL/beat, p = 0.854) or controls (93 ± 9 vs 95 ± 21 mL/beat, p = 0.648).

Conclusions

During exercise in repaired TOF subjects with dilated RV and free PR, increased total RV output per minute was facilitated by an increase in heart rate, an increase in RV FAC and a decrease in PR fraction.     

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot

Background

Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity.

Methods and results

NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7–33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p < 0.001) and RV systolic dysfunction (r = − 0.195, p = 0.022), but more strongly with LV systolic dysfunction (r = − 0.367, p < 0.001), which was present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found.

Conclusions

NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration.     

Three-Dimensional Speckle Tracking of the Right Ventricle : Toward Optimal Quantification of Right Ventricular Dysfunction in Pulmonary Hypertension

Background

Quantitative assessment of right ventricular (RV) systolic function largely depends on right ventricular ejection fraction (RVEF). Three-dimensional speckle tracking (3D-ST) has been used extensively to quantify left ventricular function, but its value for RV assessment has not been established.

Objectives

This study sought to prospectively assess whether 3D-ST would be a reliable method for assessing RV systolic function and whether strain values were associated with survival.

Methods

Comprehensive 2-dimensional echocardiographic assessment, 3D-ST of the RV free wall, and measurement of RVEF was performed in 97 consecutive patients with established pulmonary hypertension (PHT) (RVEF 31.4 ± 9.6%, right ventricular systolic pressure [RVSP] 76.5 ± 26.2 mm Hg) and 60 healthy volunteers (RVEF 43.8 ± 9.4%, RVSP 25.9 ± 4.3 mm Hg).

Results

Area strain (AS) (−24.3 ± 7.3 vs. −30.8 ± 7.2; p < 0.001), radial strain (23.2 ± 14.4 vs. 34.9 ± 18.2; p < 0.001), longitudinal strain (LS) (−15.5 ± 3.8 vs. −17.9 ± 4.4; p = 0.001), and circumferential strain (CS) (−12.2 ± 4.5 vs. −15.7 ± 6.1; p < 0.001) were all reduced in patients with PHT, compared with normal individuals. AS and CS strongly correlated to RVEF (r = 0.851, r = −0.711; p < 0.001). Systolic dyssynchrony index was greater in PHT (0.14 ± 0.06 vs. 0.11 ± 0.07; p = 0.003) and correlated to RVEF (r = −0.563, p < 0.001). AS (hazard ratio [HR]: 3.49; 95% confidence interval [CI]: 1.21 to 7.07; p = 0.017), CS (HR: 4.17; 95% CI: 1.93 to 12.97; p < 0.001), LS (HR: 7.63; 95% CI: 1.76 to 10.27; p = 0.001), and RVEF (HR: 2.43; 95 CI: 1.00 to 5.92; p = 0.050) were significant determinants of all-cause mortality. Only AS (p = 0.029) and age (p = 0.087) were predictive of death after logistic regression analysis.

Conclusions

PHT patients have reduced RV strain patterns and more dyssynchronous ventricles compared with controls, which was relatable to clinical outcomes. AS best correlated with RVEF and provides prognostic information independent of other variables.     

5-year serial follow-up of clinical condition and ventricular function in patients after repair of tetralogy of Fallot

Objective

To study the changes over time in biventricular size and function, and clinical parameters in patients after repair of tetralogy of Fallot (TOF) without subsequent pulmonary valve replacement (PVR).

Methods

We prospectively included 78 non-PVR patients (age 20(6–60)years at baseline), who were studied twice with a 5-year interval. Patients underwent magnetic resonance imaging for assessment of biventricular size and function. Exercise testing and electrocardiography were performed to determine peak oxygen uptake (peak VO₂) and QRS duration. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was assessed additionally.

Results

Pulmonary regurgitation (PR), right ventricular (RV) volumes and QRS duration increased during 5-year follow-up (RV end-diastolic volume (EDV) 130 ± 30 ml/m² to 138 ± 34 ml/m²; QRS 132 ± 27 msec to 139 ± 27 msec); peak VO₂ decreased (96 ± 19% to 91 ± 17%). RV ejection fraction, RV effective stroke volume (eff.SV), and NT-proBNP levels remained unchanged. The slope of RVEDV increase was 1.6 ± 3.0 ml/m²/year, and depended on RVeff.SV, not on RVEDV, at baseline. Increase in RVEDV correlated with increase in QRS duration over time (r = 0.28, p = 0.016), and with decrease in RV mass/EDV ratio over time (r = − 0.42, p < 0.001), not with decrease in peak VO₂. In subgroup analysis, patients with larger RVs at baseline showed larger increase in PR during follow-up and larger decrease in NYHA class over time.

Conclusions

In TOF patients with moderate RV dilatation, RVEDV increased by 1.6 ± 3.0 ml/m²/year, irrespective of RV size at baseline, but depended on RVeff.SV at baseline. Despite limited progression in RV size, unfavourable changes occurred during 5 years follow-up, which suggests there is a need for close follow-up.     

Association of VKORC1 −1639 G > A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus

Aims

Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can lead to calcification. We examined a potential association between VKORC1 −1639 G > A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima-media thickness (cIMT).

Methods

VKORC1 −1639 G > A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR-RFLP. cIMT was measured in a subgroup of 118 T2DM patients.

Results

The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly (p = 0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p = 0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 −1639 G > A polymorphism was an independent predictor of cIMT (p = 0.029) after adjusting for established risk factors.

Conclusions

The association between VKORC1 −1639 G > A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 −1639 G > A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.     

Circulating biomarkers of collagen type I metabolism mark the right ventricular fibrosis and adverse markers of clinical outcome in adults with repaired tetralogy of Fallot

Background

Right ventricular (RV) fibrosis is common in patients with repaired tetralogy of Fallot (rTOF). Although accumulating evidence indicates the role of circulating biomarkers of collagen metabolism in left ventricular fibrosis, rTOF data are lacking. This study examined the expression profile and clinical relevance of circulating biomarkers of collagen type I metabolism in rTOF patients.

Methods

Serum biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I, PICP), degradation (carboxy-terminal telopeptide of collagen type I, CITP), and enzymes regulating collagen degradation (matrix metalloproteinases, and type I tissue inhibitor, TIMP-1) were measured in 70 rTOF and 91 control adults. All patients had complete clinical data and received cardiovascular magnetic resonance scans with late gadolinium enhancement (LGE).

Results

Compared to the controls, rTOF patients had higher PICP levels (p < 0.001), PICP:CITP ratios (p < 0.001), and TIMP-1 concentrations (p < 0.001). Increasing PICP levels correlated with higher RV LGE scores (r = 0.427, p < 0.001), lower VO₂max (r = − 0.428, p = 0.002), and larger RV volumes. Furthermore, stepwise multivariate linear regression analysis identified RV end-diastolic volume index > 150 mL/m² (β = 40.52, p = 0.016), RV LGE score (β = 3.94, p = 0.008), and age (β = − 1.77, p = 0.011) as independent correlates of circulating PICP levels.

Conclusions

Patients with rTOF exhibited a profibrotic state with excessive collagen type I synthesis and dysregulated degradation. Elevated circulating PICP levels might reflect RV fibrosis, and link to adverse markers of clinical outcome.     

N-terminal Pro brain natriuretic peptide is a reliable biomarker of reduced myocardial contractility in patients with lamin A/C gene mutations

Background

Recently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations.

Methods

We prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age-sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE).

Results

Twenty-three patients were included (10 males, mean age 39.2 ± 18.9 years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123 ± 229 versus 26 ± 78 pg/ml, p = 0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341 ± 1032 pg/ml versus 80 ± 79 pg/ml in patients with normal myocardial contractility, p = 0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697-1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125 pg/ml.

Conclusion

NT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients.     

dGlucose is linked to renal function changes in diabetes

Aims

This study examines if dglucose, two-hour postprandial (2hPP) minus fasting glucose (F), predicts glycemic control better than F or 2hPPglucose.

Methods

F and 2hPPglucose, and renal function variables; BUN, serum creatinine (Scr), and estimated GFR (eGFR), were obtained from 56 insulin treated diabetic adults. 2hPP-F(d) was calculated. Variables were compared when 2hPPglucose was <200 (n = 23) or >200 mg/dL (n = 33). Correlation coefficients were calculated for F, 2hPP or 2hPP-F(d) renal function variables versus those for glucose.

Results

Variables differed significantly between F and 2hPP (t-test, p < 0.05) for all patients and when 2hPPglucose was < or >200 mg/dL, except dBUN at <200 mg/dL. When F, 2hPP or 2hPP-F(d) variables between 2hPPglucose < and >200 mg/dL were compared, dScr was significant (p = 0.0327). Correlation coefficients between dglucose and dScr or deGFR, were significant for all patients (r = 0.420, p = 0.0013, and r = −0.434, p = 0.0008, respectively) and for 2hPPglucose >200 mg/dL (r = 0.523, p = 0.0018 and r = −0.513, p = 0.0023, respectively) but not 2hPPglucose <200 mg/dL. When dglucose increased by 100 mg/dL, dScr increased by 0.08 and 0.11 mg/dL, and deGFR decreased by 2.73 and 3.73 mL/min for all patients and >200 mg/dL, respectively.

Conclusions

dGlucose better predicts renal function changes than F or 2hPPglucose. Postprandial hyperglycemia (<200 mg/dL) control is crucial for renal protection in diabetes.     

Relationship between bone biochemical markers versus glucose/lipid metabolism and atherosclerosis; a longitudinal study in type 2 diabetes mellitus

Aim

Although accumulating evidence suggests that osteocalcin, which is secreted in circulation specifically from osteoblasts, is involved in glucose and lipid metabolism, it is unclear whether serum osteocalcin is associated with atherosclerosis parameter in humans.

Subjects and methods

We monitored chronological changes in bone turnover markers and a parameter of atherosclerosis, plaque score (PS), during glycemic control in Japanese patients with type 2 diabetes, and analyzed relationships among these parameters.

Results

Multiple regression analysis showed that changes in osteocalcin were negatively correlated with changes in HbA_1c (β = −0.38, p = 0.01). Baseline osteocalcin was negatively correlated with changes in triglycerides (β = −0.29, p = 0.03) and positively with changes in HDL-cholesterol (β = 0.31, p = 0.03), and that changes in osteocalcin were negatively correlated with baseline triglyceride (β = −0.35, p = 0.02). Changes in osteocalcin were positively correlated with baseline PS (β = 0.35, p = 0.01) and negatively with changes in PS (β = −0.30, p < 0.05) independent of other conventional risk factors of atherosclerosis.

Conclusion

These findings indicated the association between serum osteocalcin and glucose and lipid metabolism as well as an atherosclerosis parameter independently of other atherosclerosis-related risk factors in patients with type 2 diabetes, suggesting that osteocalcin is important for not only bone metabolism but also glucose and lipid metabolism as well as atherosclerosis.     

Local persistent hypercoagulability after sirolimus-eluting stent implantation in patients with stable angina

Background

Late stent thrombosis (LST) after sirolimus-eluting stent (SES) implantation has been demonstrated previously. Although incomplete neointimal coverage after SES implantation has been reported, local long-term hypercoagulability remains unknown.

Methods

We evaluated the local persistent coagulative response in eighty-three consecutive patients with stable angina, treated with either SES (n = 51) or BMS (n = 32) implantation for isolated de novo left anterior descending (LAD) stenosis. We measured prothrombin fragment F1 + 2 (frF1 + 2) and D-dimer levels sampled in the coronary sinus (CS) and sinus of Valsalva (V). The transcardiac gradient (Δ) was defined as the CS level minus V level.

Results

The ΔfrF1 + 2 and ΔD-dimer were significantly greater in the SES group than in the BMS group (0.50 ± 0.35 vs −0.14 ± 0.15 nmol/l, p = 0.009 and 0.24 ± 0.21 vs −0.05 ± 0.16 μg/ml, p = 0.041, respectively). We selected the hypocoagulative [ΔfrF1 + 2 < 0.15 (mean value − SD) nmol/l, n = 21] and hypercoagulative [ΔfrF1 + 2 > 0.85 (mean value + SD) nmol/l, n = 14] groups out of the SES patients. Multivariate analysis was performed to identify independent predictors of local hypercoagulability. Total SES length was the only independent predictor of local hypercoagulability. There was a significant positive correlation between the ΔfrF1 + 2 and total stent length in the SES group (r = 0.57, p < 0.05).

Conclusions

An increased local coagulative response was observed in the convalescent phase after SES implantation as compared to BMS. Careful long-term follow-up of patients after longer SES implantation is recommended in order to avoid LST.     

Impact of human immunodeficiency virus infection on arterial stiffness and wave reflections in the early disease stages

Background

Human immunodeficiency virus (HIV) infection is associated with subclinical inflammation and increased cardiovascular risk. Arterial stiffness and enhanced wave reflections are markers of cardiovascular disease and independent predictors of cardiovascular risk. The effect of HIV infection, per se, on aortic stiffness and wave reflections has not been clearly defined.

Methods

We studied 51 adults with a recent HIV infection, free of antiretroviral treatment and AIDS diagnosis, as well as 35 controls matched for age, sex and smoking status. Carotid-femoral pulse wave velocity (PWV) and timing of the reflected wave (Tr) were measured as indices of aortic stiffness, while aortic augmentation index (AIx) and augmented pressure (AP) were measured as indices of wave reflections.

Results

While PWV was similar in the two populations, Tr was significantly lower in HIV-infected subjects compared to controls (by 16.5 ms, p = 0.002). In addition, AIx and AP were decreased (by 6.4%, p = 0.048 and by 3.3 mmHg, p = 0.010, respectively) in subjects with HIV infection. Moreover, HIV-infected patients compared with controls had increased values of hs-CRP [1.37 (0.85-2.53) vs. 0.75 (0.41-1.90) mg/l, p = 0.007] and interleukin-6 [1.90 (0.91-3.9) vs. 1.28 (0.80-2.65) pg/ml, p = 0.048]. Tr was negatively correlated with hs-CRP (r = −0.283, p = 0.010) and interleukin-6 (r = −0.278, p = 0.018).

Conclusions

Our study provides evidence of decreased wave reflections and similar aortic stiffness, as assessed by PWV, in the early stages of HIV infection in treatment-naive patients compared to controls. Subclinical inflammation and resultant peripheral vasodilatation constitute potential mediators of the whole pathophysiological process.     

Two-month effects of individualized exercise training with or without caloric restriction on plasma adipocytokine levels in obese female adolescents

Objectives

To examine if, in young obese patients, an individualized training programme in association with a caloric restriction programme which had an effect on whole-body lipid oxidation, was able to induce changes on plasma adipocytokine concentrations.

Materials and methods

Twenty-seven obese female adolescents participated in the study. Whole-body lipid oxidation during exercise was assessed by indirect calorimetry during a graded cycle ergometer test. Body mass (BM), body mass index (BMI), percentage of body fat (%BF), insulin homeostasis model assessment (HOMA-IR) and fasting levels of circulating adipocytokines were assessed prior and after a two-month diet programme, individualized training programme targeted at Lipox_max corresponded to the power at which the highest rate of lipids was oxidized and combined diet/training programme.

Results

The diet/training programme induced both a shift to a higher-power intensity of Lipox_max (+27.8 ± 5.1 W; p < 0.01) and an increase of lipid oxidation at Lipox_max (+96.8 ± 16.2 mg/min; p < 0.01). The enhancement in lipid oxidation was significantly (p < 0.01) correlated with the diet/training-induced improvement in %BF (r = −0.47), HOMA-IR (r = −0.66), leptin (r = −0.41), TNF-α (r = −0.48), IL-6 (r = −0.38), adiponectin (r = 0.43) and resistin (r = 0.51).

Conclusion

This study showed that in obese female adolescents a moderate training protocol targeted at Lipox_max and combined with a diet programme improved their ability to oxidize lipids during exercise, and that this improvement was associated with changes in plasma adipocytokine concentrations.