Lower Left Ventricular Wall Thickness Research Articles

Cardiac MRI shows an association of lower cardiorespiratory fitness with decreased myocardial mass and higher cardiac stiffness in the general population – The Sedentary's Heart

BackgroundThe heart has the capacity to adapt to different demands. The pathophysiological mechanisms involved with sedentarism are not fundamentally the opposite of those related with physical activity and regular exercise. We investigated the impact of lower cardiorespiratory fitness (CRF) on heart's plasticity and function in a population-based setting. MethodsWe used data from 1165 participants (539 women; 46.3%) aged 21–81 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the cross-sectional associations of peak oxygen uptake (VO2peak), determined by symptom-limited cardiopulmonary exercise testing, with structural and functional left ventricular (LV) and left atrial (LA) parameters determined by magnetic resonance imaging (MRI) using multivariable- adjusted linear regression models. ResultsA 1 L/min lower VO2peak was associated with a 10.5 g (95% confidence interval: 8.00 to 12.9; p < 0.001) lower LV mass, a 14.8 mL (10.9 to 18.6; p < 0.001) lower LV end-diastolic volume, a 0.29 mm (0.19 to 0.40; p < 0.001) lower LV wall-thickness, a 8.85 mL/beat (6.53 to 11.2; p < 0.001) lower LV stroke volume, a 0.42 L/min (0.25 to 0.60; p < 0.001) lower LV cardiac output and a 7.51 mL (3.88 to 11.1; p < 0.001) lower LA end-diastolic volume. Moreover, there were no associations with a concentric or eccentric remodeling and LV and LA ejection fraction. ConclusionsLower CRF was associated with a smaller heart, LV wall-thickness and mass, LV and LA stroke volume and cardiac output. Conversely, there was no association with LA and LV ejection fraction. Our cross-sectional observations are consistent with cardiac adaptations reflecting reduced volume loading demands of a sedentary lifestyle – “the sedentary's heart”.

Borderline-low testosterone levels are associated with lower left ventricular wall thickness in firefighters: An exploratory analysis.

BackgroundLow endogenous testosterone has been associated with increased cardiovascular risk in men.ObjectivesTo determine the prevalence of low serum testosterone level (TT) in a cohort of male US career firefighters and to examine its relation with left ventricular wall thickness (LVWT).Materials and MethodsWe conducted a cross‐sectional study among 341 career firefighters, (age: 37.5 ± 10.3 years; BMI: 28.9 ± 4.5 kg/m2), who underwent an occupational medical screening examination. TT quartiles were determined, and LVWT distribution among them was plotted. Then, TT values were categorized as low (<264 ng/dL), borderline (264‐399 ng/dL), reference range (400‐916 ng/dL), and high (>916 ng/dL). To further investigate the association of mildly decreased TT on LVWT, we divided the borderline group into borderline‐low (264‐319 ng/dL) and borderline‐high (320‐399 ng/dL) ranges. LVWT values were classified as low LVWT when <0.6 cm. A multivariate model was used to compare LVWT, age, BMI, systolic blood pressure (SBP), and HbA1c among groups by TT values.ResultsThe prevalence of low TT was 10.6% and of borderline was 26.4%, while 58.7% had levels in the reference range. The low‐TT group was older and had higher BMI and SBP as compared to the reference group (P < .01). LVWT values were different among groups (P = .04) and significantly lower in firefighters with borderline‐low TT as compared to the reference group (P < .05). This finding also occurred within obese firefighters (P = .03). The borderline‐low group had a higher adjusted risk for a low LVWT as compared to the reference group [OR: 4.11 (95% CI: 1.79‐9.43)].DiscussionOur findings highlight the possible relationship between a mild reduction in testosterone levels (borderline) and lower LVWT.ConclusionsA high prevalence of subnormal TT levels (low and borderline: 37%) was observed in this relatively homogeneous cohort of career firefighters. Mildly decreased TT levels and lower LVWT might represent a preclinical condition and a window of opportunity for cardiovascular preventive interventions in firefighters.

P4428Physical exercise during uncontrolled systemic arterial hypertension

Abstract Introduction Physical exercise reduces systemic arterial blood pressure and improves cardiac remodeling. However, the effects of exercise during uncontrolled arterial hypertension remains poorly understood. This study evaluated the influence of physical training on cardiac remodeling in untreated spontaneously hypertensive rats (SHR). Methods Four experimental groups were used: sedentary (W-SED n=27) and trained (W-EX, n=31) normotensive Wistar rats, and sedentary (SHR-SED, n=27) and exercised (SHR-EX, n=32) hypertensive rats. At 13 months old, the exercise groups underwent treadmill exercise five days a week, for four months. Echocardiogram was performed to evaluate cardiac structures and function. In vitro myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen was quantified by histology and hydroxyproline concentration and antioxidant enzyme activity was assessed by spectrophotometry. NADPH oxidase activity was analyzed by lucigenin reduction. Protein expression was quantified by Western blot. Matrix metalloproteinases (MMP) activity was evaluated by zymography. Statistical analyzes: two factor ANOVA and Bonferroni or Kruskal-Wallis and Dunn tests. Results Systolic blood pressure was higher in SHR groups. Exercised groups had greater physical capacity. Frequency of heart failure features was higher in hypertensive groups than controls; SHR-EX had a lower frequency of pleural effusion and tachypnea than SHR-SED. Echocardiogram showed lower LV wall thickness, LV relative wall thickness, left atrium diameter, and relaxation time in SHR-EX than SHR-SED. Myocardial function was better in SHR-EX (positive derivative of developed tension) than SHR-SED. SHR-EX had higher antioxidant enzyme activity than SHR-SED. Lipid hydroperoxide concentration, myocyte diameters, and phosphorylated JNK and total IkB protein expression were higher in hypertensive than control groups. Hydroxyproline, malondialdehyde, NADPH oxidase activity, and protein expression of collagen III, lysyl oxidase, TIMP-1, total JNK, phosphorylated p38, phosphorylated and total p65, and phosphorylated IkB did not differ between groups. Interstitial collagen fraction, MMP-2 activity, and protein expression of total p38, and total and phosphorylated ERK were higher in SHR-SED than W-SED. Exercise reduced MMP-2 activity and phosphorylated ERK in hypertensive rats. Conclusion Physical exercise improves physical capacity, reduces the frequency of heart failure features, and attenuates cardiac remodeling in spontaneously hypertensive rats. In addition, exercise increases antioxidant enzyme activity, decreases ERK phosphorylation and MMP-2 activity, and attenuates total ERK protein expression. Acknowledgement/Funding Fapesp, CNPq, Capes and UNESP

Cardiovascular Health Status and Incidence of Heart Failure in the Framingham Offspring Study.

The American Heart Association Cardiovascular Health (CVH) score is inversely associated with cardiovascular disease, but its relations to cardiac remodeling traits and heart failure (HF) incidence have not been examined. A 14-point score was constructed for each participant based on the presence of poor, intermediate, or ideal status on each of the 7 CVH metrics (ideal score=14). We related the CVH score to echocardiographic traits cross-sectionally and to HF incidence prospectively in the Framingham Offspring Study. In age- and sex-adjusted models, a higher CVH score was associated with lower left ventricular (LV) mass, LV wall thickness, LV diastolic dimension, and left atrial dimension (P<0.01 for all; n=2392; mean age, 58 years; 56% women), and with a 12% to 15% lower odds of prevalent LV concentric remodeling and concentric hypertrophy, respectively (P<0.0001 for both). On follow-up (mean, 12.3 years), 188 incident HF events were observed in 3201 participants (mean age, 59 years; 53% women). In age- and sex-adjusted Cox proportional hazard models, the CVH score was inversely associated with HF incidence (hazard ratio per 1-point higher CVH score, 0.77; 95% confidence interval, 0.72-0.83). This association was partially attenuated upon adjustment for LV mass and interim myocardial infarction (hazard ratio, 0.84; 95% confidence interval, 0.76-0.93), and it was consistent for HF with preserved and reduced ejection fractions. In our community-based sample, comprised predominantly of middle-aged white individuals of European descent, better CVH was associated with lower HF incidence, in part due to a lower prevalence of adverse cardiac remodeling.

Titin: a phenotype-genotype descriptive comparison of dilated cardiomyopathy

Background Cardiovascular magnetic resonance (CMR) imaging is the gold standard imaging modality for characterization of dilated cardiomyopathy (DCM). We recently identified genetic variants that truncate the giant protein Titin (TTN) accounting for up to 25% of DCM cases: a discovery that will increase the utility of genetic testing and family screening in DCM. However, the clinical consequences of TTN truncating variants (TTNtv) are unknown. Here, we integrated the power of CMR and capacity of next generation sequencing (NGS) to assess the relationship between genotype and phenotype in a non-ischemic DCM population. Methods 319 patients referred for characterization of DCM were recruited and underwent quantitative CMR study with detailed phenotyping (Siemens Avanto or Siemens Sonata 1.5T scanners). Additional clinical data were collected. TTN genotypes were determined by target enrichment using SureSelect and NGS sequencing using the SOLiD 5500 platform. Results TTN truncating variants (TTNtv) were identified in 13% (n = 42) of cases, the commonest genetic cause of DCM. Table 1 compares the CMR and clinical characteristics of TTNtv-positive and TTNtv-negative cohorts. TTNtv-positive DCM patients had lower left ventricular (LV) ejection fraction (EF) (p = 0.02), thinner LV walls (p < 0.02) and higher incidence of sustained ventricular tachycardia (VT) (p = 0.001) which was independent of EF. No statistically significant difference in the prevalence of midwall fibrosis existed between the two groups. Multivariate linear regression models that considered age, sex, TTNtv presence and position (distance from the protein N-terminus) indicated that TTNtv position was significantly correlated with biventricular ejection fraction and indexed stroke volumes such that more distal truncations had worse indices of cardiac function. For example, a C-terminal TTNtv would be associated with an absolute reduction in LV EF of 18 ± 7%, (p = 0.005), as compared with an N-terminal TTNtv. Conclusions These data highlight the prevalence of TTNtv in this unselected DCM cohort and suggest that TTNtvpositive DCM patients may benefit from tailored clinical management. Sustained VT, LV wall thickness and LVEF influence DCM outcomes. The increased risk of sustained VT in TTNtv-positive DCM may warrant a lower threshold for device therapy, as recommended for DCM caused by LMNA mutations. As distal TTNtv were associated with worse LV function, more aggressive clinical management may be appropriate in patients carrying these variants. The phenotypic expression of genetic substrates can be highly variable, and CMR is central to the accurate phenotypic description of this common yet heterogenous condition. Enhanced molecular understanding may lead to strategies to alter disease course beyond current pharmacological and device based therapy.

Myocardial function in children after fetal chemotherapy exposure. A tissue Doppler and myocardial deformation imaging study

Chemotherapy and particularly anthracycline exposure are associated with acute and chronic cardiotoxicity. Few data exist on the effect of cardiac function after in utero exposure to maternal chemotherapy. Our recently published multicenter prospective study showed no significant changes in systolic function using conventional echocardiographic parameters. The purpose of this study was to further investigate whether early functional changes can be detected using tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE). Sixty-two children (median/range age 1.7 (1-9.8) years) exposed to chemotherapy during fetal life were enrolled and compared to 62 age- and gender-matched controls. TDI velocities were measured at the basal interventricular septum (IVS) and right and left ventricular (LV) free walls. LV global longitudinal and circumferential systolic strains were derived using 2D STE. We found small but significant differences between the groups (patients versus controls) in LV fractional shortening [35 (29-46)% versus 39 (28-53)%, p < 0.001], LV ejection fraction [66 (57-79)% versus 70 (57-83)%, p < 0.001], LV posterior wall thickness z score [-0.15 (-2.32-1.81) versus -0.10 (-1.9-2.0), p < 0.001], and IVS thickness z score [-1.06 (-2.6-1.3) versus -0.5 (-2.1-1.7), p < 0.001]. No significant differences in TDI velocities or LV global strains were observed. Within the patient group, the cardiac functional parameters did not correlate to the number of cycles of anthracycline or the cumulative anthracycline dose. Children exposed to fetal chemotherapy have a lower normal fractional shortening and mildly lower left ventricular wall thickness. Tissue Doppler and strain measurements are within normal range and not statistically different from normal controls. The long-term implications of these findings will be further studied in this prospective cohort study.

Reduced Survival in Patients with “Coronary Microvascular Disease”

The syndrome of chest pain, abnormal stress test, and nonflow limiting coronary artery disease (CAD) is common and is attributed to coronary microvascular disease (µVD). It is associated with increased hospital admissions and health care costs. But its impact on long-term survival is not known. Of the 9941 consecutive patients who had an exercise stress test for evaluation of chest pain between May 1991 and July 2007, 935 had both a positive stress test and a coronary angiogram within 1 year of their stress test forming the study cohort. Significant angiographic CAD defined as ≥70% stenosis of an epicardial coronary artery or ≥50% stenosis of the left main coronary artery was present in 324 patients. Rest (n = 611) were considered to have coronary µVD. Compared with patients with significant epicardial CAD, patients with coronary µVD were younger (63 ± 11 vs. 65 ± 10 years, p = 0.002), and had lower left ventricular wall thickness (p < 0.02), systolic blood pressure (BP; p = 0.002), pulse pressure (0.0008), systolic BP with exercise (p = 0.0001), and pulse pressure with exercise (p < 0.0001). Those with coronary µVD had a better survival compared with those with significant epicardial CAD, but worse than that expected for age- and gender-matched population (p < 0.0001). Coronary µVD as a cause of chest pain and positive stress test is common. All-cause mortality in patients with coronary µVD is worse than in an age- and gender-matched population control, but better than those with significant epicardial CAD.

Toll-Like Receptor 6 Ser249Pro Polymorphism Is Associated With Lower Left Ventricular Wall Thickness and Inflammatory Response in Hypertensive Women

Experimental data demonstrated that inactivation of toll-like receptor (TLR) pathway components attenuated left ventricular (LV) remodeling induced by pressure overload. This study investigated the impact of TLR6 Ser249Pro polymorphism on LV structure in hypertensive subjects. A sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, analysis of inflammatory and metabolic parameters, echocardiography, and genotyping of the TLR6 variant. Moreover, the relationship between genotypes and in vitro responsiveness of peripheral blood monocytic cells to TLR agonists was also assessed. Homozygous women for the TLR6 249Ser allele had lower LV posterior wall thickness (9.4 + or - 0.4 vs. 10.5 + or - 0.1 mm; P = 0.02), interventricular septum thickness (9.7 + or - 0.3 vs. 10.7 + or - 0.1 mm; P = 0.03), and LV relative wall thickness (0.39 + or - 0.02 vs. 0.44 + or - 0.01; P = 0.02) than women with other genotypes. These results were confirmed by stepwise regression analyses adjusted by potential confounders. Conversely, homozygous men for the 249Ser variant showed no differences in LV structure in comparison to males carrying the 249Pro allele. In addition, monocytes from hypertensive women homozygous for the 249Ser allele showed a lower release of tumor necrosis factor-alpha and interleukin-6 in response to zymosan (TLR6 agonist), but not to lipopolysaccharide (TLR4 agonist). These data suggest that hypertensive women homozygous for the TLR6 249Ser polymorphism might exhibit lower LV wall thickness and reduced TLR6-mediated inflammatory response than females carrying the major allele.

H 003 Toll-like Receptor-6 pro249ser Polymorphism is Associated with Decreased Interleukin-6 Production and Lower Left Ventricular Wall Thickness in Hypertensive Women

Toll-like receptors (TLRs) play a pivotal role in an innate immunity system, which controls inflammation responses and further instructs development of adaptive immunity. We enrolled 250 Han Chinese in Taiwan screening for the single nucleotide polymorphisms (SNPs) in TLRs associated with viral infection, including TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9. The 6 SNPs not hitherto identified in Chinese populations, including TLR3 1377 C>T, TLR3 −7 C>A, TLR7 Gln11Leu, TLR7 IVS1+1817 G>T, TLR8 Met1Val, and TLR8 −129 G>C, had minor allele frequencies of 38%, 23%, 22.3%, 3%, 16.0%, and 16.0%, respectively. The frequencies of 2 common SNPs, TLR9, −1486 T>C and 2848 G>A, were 28% and 44%, respectively. As compared with other ethnic populations, Chinese displayed an opposite allele frequency of TLR8 Met1Val and TLR8 −129 G>C to Caucasians and African Americans. In addition, TLR2 Arg677Try, TLR2 Arg753Gln, TLR4 Asp299Gly, and TLR4 Thr399Ile that were apparent in approximately 10% of Caucasians were not detected in Chinese. In conclusion, obvious ethnic differences in TLR polymorphisms may in part reflect the ethnic diversity of host viral susceptibility.

Cardiac Involvement in Thyroid Hormone Resistance

To analyze the cardiovascular alterations thought to occur in resistance to thyroid hormone (RTH), cardiac involvement in 54 patients with RTH was investigated with the help of two-dimensional and Doppler echocardiography. Data from 41 of 54 adult subjects with RTH were also compared with those of 24 and 20 cases with hyperthyroidism (H) and hypothyroidism (h), respectively, as well as 22 healthy euthyroid controls (C). With respect to the type of mutations, no correlation was found between cardiovascular features and genotype. Compared with affected adults, children with RTH showed markedly higher serum free T3 (FT3), free T4 (FT4), and baseline TSH concentrations. Compared with healthy children of comparable age, RTH children had significantly higher heart rate and lower left ventricular (LV) ejection fraction (P = 0.006). Also, higher heart rate and FT4 as well as shorter diastolic relaxation of the myocardium (all P = 0.001) between RTH subjects with and without thyrotoxic cardiovascular features were found. Cardiac symptoms (palpitations, 32% vs. 71%) and signs (sinus tachycardia, 26% vs. 79%; atrial fibrillation, 6% vs. 17%) were significantly less frequent in RTH vs. H (all P = 0.001). Compared with C and h, heart rate, cardiac output, stroke volume, and systolic aortic flow velocity were strongly increased in RTH (all P = 0.0001) and H, although ejection (P = 0.0012) and shortening (P = 0.0001) fractions of the LV were markedly lower in RTH vs. H. Diastolic parameters, such as isovolumic relaxation (P = 0.0001) and deceleration time (P = 0.013), were shorter in RTH vs. h and C. In RTH, positive correlations between FT3 and heart rate, and between FT4 and LV ejection fraction were observed, whereas negative correlations between both FT3 and FT4 and isovolumic relaxation were noted. In conclusion, these findings indicate a modulated hyperthyroid effect on cardiac systolic and diastolic function of the myocardium in RTH, whereas other parameters, such as ejection and shortening fractions of the LV, systolic diameter, and LV wall thickness, were comparable to C. Differences in term of cardiovascular changes were smaller between the RTH and C groups than the RTH and the H or h groups. Thus, an incomplete cardiac response to thyroid hormone is present in RTH.