Marie-Christine Herregods

Prevalence of Left Ventricular Diastolic Dysfunction in a General Population

Background—Because the process of myocardial remodelling starts before the onset of symptoms, recent heart failure (HF) guidelines place special emphasis on the detection of subclinical left ventricular (LV) systolic and diastolic dysfunction and the timely identification of risk factors for HF. Our goal was to describe the prevalence and determinants (risk factors) of LV diastolic dysfunction in a general population and to compare the amino terminal probrain natriuretic peptide level across groups with and without diastolic dysfunction. Methods and Results—In a randomly recruited population sample (n=539; 50.5% women; mean age, 52.5 years), we measured early and late diastolic peak velocities of mitral inflow (E and A), pulmonary vein flow by pulsed-wave Doppler, and the mitral annular velocities (Ea and Aa) at 4 sites by tissue Doppler imaging. A healthy subsample of 239 subjects (mean age, 43.7 years) provided age-specific cutoff limits for normal E/A and E/Ea ratios and the differences in duration between the mitral A and the reverse pulmonary vein flows during atrial systole (&Dgr;Ad−ARd). The number of subjects in diastolic dysfunction groups 1 (impaired relaxation), 2 (elevated LV end-diastolic filling pressure), and 3 (elevated E/Ea and abnormally low E/A) were 53 (9.8%), 76 (14.1%), and 18 (3.4%), respectively. We used &Dgr;(Ad<ARd+10) to confirm possible elevation of LV filling pressures in group 2. Compared with subjects with normal diastolic function (n=392, 72.7%), group 1 (209 versus 251 pmol/L; P=0.015) and group 2 (209 versus 275 pmol/L; P=0.0003) but not group 3 (209 versus 224 pmol/L; P=0.65) had a significantly higher adjusted NT-probrain natriuretic peptide. Higher age, body mass index, heart rate, systolic blood pressure, serum insulin, and creatinine were significantly associated with a higher risk of LV diastolic dysfunction. Conclusions—The overall prevalence of LV diastolic dysfunction in a random sample of a general population, as estimated from echocardiographic measurements, was as high as 27.3%.

Left ventricular strain and strain rate in a general population

AIMS Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup. METHODS AND RESULTS In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s(-1)) and radial (3.40 s(-1)) SR decreased with age (P </= 0.007). Longitudinal and radial strain independently decreased (P </= 0.006) with relative wall thickness (RWT), longitudinal strain with the waist-to-hip ratio, and radial strain with body weight. In contrast, LV ejection fraction increased (P </= 0.0001) with age and RWT. Longitudinal and radial stain rate increased with heart rate (P </= 0.05). In healthy subgroup (n = 236), the fifth percentiles were 18.4 and 44.3%, and 0.99 and 2.43 s(-1), for longitudinal and radial strain and SR, respectively. CONCLUSION We explored the early signs of LV systolic dysfunction in a general population, using tissue Doppler imaging technique. LV strain and SR decrease with age, body weight, central obesity, and RWT. Our current study resulted in the proposal for diagnostic thresholds for strain and SR, based on a healthy subgroup recruited via random sampling of the population.

Durability of mitral valve repair in Barlow disease versus fibroelastic deficiency

OBJECTIVE Durability assessment of mitral valve repair for degenerative valve incompetence is limited to reoperation as a primary indicator and valve-related risk factors for late death as a secondary indicator. We assessed serial echocardiographic follow-up of valve function as an indicator of the durability of mitral valve repair. METHODS AND RESULTS In 348 patients having undergone mitral valve repair for degenerative valve incompetence, clinical outcome was excellent: 10 years after repair, survival was 80.1% and freedom from reoperation 94.4%. However, freedom from mitral regurgitation (>2/4), 98.7% at 1 month, decreased to 82.2% at 5 years and 64.9% at 10 years. The linearized recurrence rate of mitral regurgitation (>2/4) was 3.2% per year. Recurrence rate was higher in patients with Barlow disease (6.0%) and lower in those with fibroelastic deficiency (2.6%) (P = .01). Performing chordal shortening, the nonuse of sliding plasty and the nonuse of an annuloplasty ring were determined to be factors predicting recurrence of mitral regurgitation. In reconstructions avoiding these risk factors, recurrence rate decreased to 2.4%. There was no difference between Barlow disease and fibroelastic deficiency: 2.9% versus 2.2% (P > .05). Recurrent regurgitation is characterized by leaflet prolapse, thickening, and calcification. CONCLUSION When optimal surgical techniques are used, the residual recurrence rate of mitral valve regurgitation remains between 2% and 3% per year and is related to progressive degeneration of the chordae and the leaflets. Long-term results of mitral valve repair in Barlow disease are essentially the same as in fibroelastic deficiency.

Functional Recovery of Subepicardial Myocardial Tissue in Transmural Myocardial Infarction After Successful Reperfusion: An Important Contribution to the Improvement of Regional and Global Left Ventricular Function

BACKGROUND The transmural extent of myocardial necrosis after an acute coronary artery occlusion can vary considerably. The contribution of residual subepicardial viable myocardium to global left ventricular function is largely unknown. METHODS AND RESULTS We studied 12 patients with single-vessel disease 1 week after successful reperfusion of a first transmural anterior myocardial infarction (MI). With PET, myocardial blood flow (MBF) and glucose metabolism were measured regionally, and the viability was graded as normal, mismatch, or match with severely (<50% of normal) or intermediately (50% to 80% of normal) impaired MBF. Magnetic resonance tagging was used to regionally quantify fiber strains, wall thickening, and ejection fraction in patients 1 week and 3 months after the MI and in age-matched healthy volunteers. From 1 week to 3 months, subepicardial fiber shortening improved significantly in the match region (MBF <50%, -5.1+/-7.0% to -9.9+/-8. 7%; MBF of 50% to 80%, -7.1+/-7.6% to -14.9+/-7.9%). This was associated with an improvement in regional ejection fraction in the infarcted myocardium (29.6+/-21.8% to 43.5+/-15.5%, P<0.0001) and in normal regions (54.3+/-15.1% to 56.5+/-13.1%, P=0.013), contributing to an increase in global ejection fraction from 44.2+/-22.2% to 49. 3+/-17.9% (P<0.0001). CONCLUSIONS Functional recovery of viable subepicardial regions is a mechanism of late improvement in regional and global ejection fraction after a so-called transmural MI.

Intravascular ultrasound versus angiography for measurement of luminal diameters in normal and diseased coronary arteries

Quantitation of coronary luminal diameter with a 20 MHz mechanically rotating intravascular ultrasound (IVUS) catheter was compared with orthogonal-view cineangiography by use of a semiautomated edge-detection algorithm in 48 patients undergoing coronary angioplasty. Quantitative comparison of 196 matched segments was attempted, but in only 174 (88.8%) was a direct comparison of the two techniques possible. In angiographically normal coronary arteries (46 segments) the correlation between the values obtained by quantitative coronary angiography (QCA) and those achieved by IVUS was excellent (r = 0.92, p < 0.0001). For mild stenoses (80 segments) the correlation coefficient was only fair (r = 0.467, p < 0.001). After percutaneous transluminal coronary angioplasty the correlation coefficient between IVUS and QCA data (48 segments) was very weak (r = 0.282, p < 0.05). In conclusion, coronary IVUS is feasible and safe and even for a limited range of coronary arterial narrowing, significant correlations between IVUS and QCA measurements of minimal lumen diameter were found. They were excellent in normal coronary arteries, moderate in mildly diseased arteries, and weak after balloon angioplasty.

Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice.

Background—Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown. Methods and Results—We studied the effect of diet restriction–induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator–activated receptors (PPAR)-&agr; and PPAR-&ggr; expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-&agr; and PPAR-&ggr;, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-&agr; and PPAR-&ggr; expression was inversely related to plaque volume and to oxidized LDL content in the plaques. Conclusions—Induction of PPAR-&agr; and PPAR-&ggr; in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome.

(18)F-FDG PET/CT for early detection of embolism and metastatic infection in patients with infective endocarditis.

PurposeIn the acute setting of endocarditis it is very important to assess both the vegetation itself, as well as potential life-threatening complications, in order to decide whether antibiotic therapy will be sufficient or urgent surgery is indicated. A single whole-body scan investigating inflammatory changes could be very helpful to achieve a swift and efficient assessment.MethodsIn this study we assessed whether 18F-FDG can be used to detect and localize peripheral embolism or distant infection. Twenty-four patients with 25 episodes of endocarditis, enrolled between March 2006 and February 2008, underwent 18F-FDG PET/CT imaging on a dedicated PET/CT scanner.ResultsPET/CT imaging revealed a focus of peripheral embolization and/or metastatic infection in 11 episodes (44%). One episode had a positive PET/CT scan result for both embolism and metastatic infection. PET/CT detected seven positive cases (28%) in which there was no clinical suspicion. Valve involvement of endocarditis was seen only in three patients (12%).ConclusionPET/CT may be an important diagnostic tool for tracing peripheral embolism and metastatic infection in the acute setting of infective endocarditis, since a PET/CT scan detected a clinically occult focus in nearly one third of episodes.

Prosthesis-Patient Mismatch Predicts Structural Valve Degeneration in Bioprosthetic Heart Valves

Background— Prosthesis-patient mismatch (P-PtM) after aortic valve replacement results in disturbed valve performance associated with increased pressure gradients. However, it is unknown whether this can be related to future structural valve deterioration (SVD) of the bioprosthesis. Methods and Results— In 564 patients (mean age, 74±5 years) receiving an aortic valve bioprosthesis, clinical follow-up (median, 6.1 years; maximum, 16.4 years) was analyzed including echocardiography. SVD was diagnosed in 40 patients (7%) as substantially increased stenosis (n=24) or regurgitation (n=16) of the operated valve over time. When patients with P-PtM (effective orifice area index <0.85 cm2/m2; n=285) developed SVD, it was preferentially of the stenosis type, whereas when patients without P-PtM (n=279) developed SVD, the majority was of the incompetence type (P<0.05). Multivariable analysis including patient- and valve-related variables revealed that P-PtM and label size ≤21 were independent predictors of SVD (P=0.04 and P=0.02, respectively). A nonparametric Turnbull estimate analysis showed that SVD is virtually nonexistent for up to 9 years in patients without P-PtM. Thereafter, SVD starts to occur and is mainly of the incompetence-type SVD (79% of cases). In patients with P-PtM, SVD starts to occur after 2 to 3 years after implantation and is mainly of the stenosis-type SVD (81% of cases). Conclusions— These data suggest that stenosis-type SVD is an early, P-PtM–related, and thus preventable phenomenon. Incompetence-type SVD is a time-dependent, nonspecific wear damage to bioprosthetic valves, which is not related to P-PtM.

One-dimensional ultrasonic strain and strain rate imaging: a new approach to the quantitation of regional myocardial function in patients with aortic stenosis

Abnormalities in regional left ventricular (LV) function in aortic stenosis (AS) have yet to be appropriately characterized. One-dimensional strain (epsilon) and strain rate imaging (SRI), new ultrasound (US) indices for quantifying regional wall deformation, might allow this. The aims of this study were 1. to define regional radial and longitudinal epsilon /SR in AS; 2. to establish if they are related to the severity of the disease; and 3. to determine if regional deformation is further altered by coexistent coronary artery disease (CAD). A total of 40 patients were studied: Group I with isolated AS (10 women, 10 men; mean age 66 years) and group II with AS and concomitant CAD (CAD/AS) (13 women, 7 men, mean age 68 years). Data were compared to 20 age-matched healthy people (N). Regional systolic maximal velocity/SR and end-systolic and maximal epsilon were measured. The maximal systolic velocity/SR in AS and CAD/AS patients were significantly reduced compared to N. The two patient groups could be further differentiated by end-systolic and maximal epsilon, which demonstrated a further reduction in both epsilon indices in CAD/AS (i.e., maximal radial epsilon 29.3%, AS; 23.7%, CAD/AS; 40.4%, N; AS and CAD/AS vs. N, AS vs. CAD/AS, p < 0.05). Indices of radial and longitudinal deformation correlated both with aortic valve area (AVA) and stroke volume (SV) (i.e., radial maximal epsilon and AVA, r = 0.77, p < 0.05). A significant correlation was also found between epsilon indices and the severity of left anterior descending (LAD) or circumflex artery (CX) coronary artery. Regional myocardial deformation in AS is abnormal. In the absence of CAD, the degree of abnormality correlates with aortic valve area (AVA). The severity of the disease was best expressed by changes in regional epsilon. In CAD/AS patients, there was a significant further reduction in end-systolic and maximal epsilon. These changes correlated with the severity of coronary narrowing in the subtending vessel.

Enhanced left ventricular endocardial border delineation with an intravenous injection of SonoVue, a new echocardiographic contrast agent : A European multicenter study.

The safety and efficacy of SonoVue (also referred to as BR1), a new contrast agent for delineating endocardial border of the left ventricle after intravenous administration, was assessed. Two hundred and eighteen patients with suspected coronary artery disease undergoing fundamental echocardiography for the assessment of left ventricle were enrolled in a prospective multicenter, single blind, cross‐over study with random sequence allocation of four different doses of SonoVue. Endocardial border definition in the apical and parasternal views was scored as O = not visible, 1 = barely visible, and 2 = well visualized before and after contrast enhancement. Analysis was performed by two pairs of off‐site observers. Safety of SonoVue was also assessed. Results of our study indicated that the mean improvements in the endocardial border visualization score were as follows: 3.1 ± 7.8 (95% CI, 2.5 and 3.7) for 0.5 ml, 3.4 ± 8.0 (95% CI, 2.8 and 4.0) for 1 ml, 3.4 ± 7.9 (95% CI, 2.8 and 4.0) for 2 ml, and 3.7 ± 8.0 (95% CI, 3.1 and 4.3) for 4 ml (P < 0.05 for all doses from baseline). Changes from baseline in endocardial visualization scores were also seen in the apical views (P < 0.05) and they were dose‐dependent (P < 0.001). Similar enhancements of endocardial visualization scores were observed in the apical views in patients with suboptimal baseline echocardiographic images. Diagnostic confidence for assigning a score and image quality also were significantly better following contrast enhancement. No significant changes in the laboratory parameters and vital signs were noted following contrast enhancement, and the side effects were minimal. It was concluded that SonoVue is safe and effective in delineating endocardial border, including in patients with suboptimal baseline images.