Increase In Left Ventricular Wall Thickness Research Articles

Myocardial Tissue Characterization in Danon Disease.

HomeRadiologyVol. 307, No. 2 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyMyocardial Tissue Characterization in Danon DiseaseFei Chen, Mao Chen Fei Chen, Mao Chen Author AffiliationsFrom the Department of Cardiology, Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, PR China.Address correspondence to M.C. (email: [email protected]).Fei ChenMao Chen Published Online:Jan 17 2023https://doi.org/10.1148/radiol.222333MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 14-year-old boy was referred for cardiac MRI, which showed mild left ventricular (LV) wall thickening to 13 mm (Figure, A). No edema signal or late gadolinium enhancement (LGE) was observed (Figure, A, B). Native myocardial T1 was elevated (1331 msec; reference, 1114–1290 msec), but extracellular volume (ECV) fraction (25%) and myocardial T2 (38 msec) were normal (Figure, C–E). LV hypertrophy associated with storage disorders was suspected.Baseline and follow-up cardiac MRI scans in a young boy with Danon disease. (A–E) Cardiac MRI scans at age 14 years show (A) mild left ventricular (LV) hypertrophy (maximum thickness, 13 mm; LV mass index, 93 g/m2) with no edema, (B) late gadolinium enhancement (LGE), (C) abnormal global native T1 value of 1331 msec (reference, 1114–1290 msec), (D) normal global extracellular volume (ECV) fraction of 25% (reference, 21%–33%), and (E) normal global T2 value of 38 msec (reference, 33–44 msec). (F–J) Cardiac MRI scans at age 19 years show (F) extreme LV hypertrophy (maximum thickness, 43 mm; LV mass index, 476 g/m2) with extensive midwall-dominant edema, (G) LGE, and (H-J) increased global tissue characterization metrics ([H] native T1 value [1478 msec], [I] extracellular volume fraction [44%], and [J] T2 value [51 msec]). CE-bSSFP = contrast-enhanced balanced steady-state free precession.Download as PowerPointOpen in Image Viewer At age 19 years, a repeated cardiac MRI showed a marked increase in LV wall thickness to 43 mm (Figure, F). LGE manifested in a nonischemic pattern of midwall-dominant involvement, sparing the basal septum, and with a base-to-apex increasing tendency (Figure, G). Myocardial T1 had increased (1478 msec) since the last examination, as had ECV fraction (44%) (Figure, H, I). T2 imaging showed myocardium edema signals and increased myocardial T2 (51 msec) (Figure, F, J).Genetic testing was indicated and identified a pathogenic mutation in the lysosome-associated membrane protein 2 (LAMP2) gene (c.190_191delGT), suggesting the diagnosis of Danon disease (1). Danon disease, or LAMP2 deficiency (glycogen type 2b storage disease), predominantly affects cardiac and skeletal muscles and also includes neurologic manifestations. It may be underrecognized as a cause of hypertrophic cardiomyopathy in childhood and early adulthood (2,3). Cardiac MRI could reveal cardiomyocyte injury, edema, and fibrosis in the progression of Danon disease, as well as isolated intracellular autophagic vacuoles accumulation during the early stage.Disclosures of conflicts of interest: F.C. No relevant relationships. M.C. No relevant relationships.

What is the Importance of Clinical Clues, and How can we Avoid Mistakes in Following Them?

Approximately half of patients with heart failure (HF) have preserved ejection fraction (EF), and approximately half of these patients have increased left ventricular (LV) wall thickness . This increase in LV wall thickness is usually attributed to left ventricular hypertrophy induced by arterial hypertension (AH). However, cardiac amyloid fibril infiltration also increases ventricular wall thickness, and it can lead to a clinical syndrome of HF with preserved EF (HFpEF). Light chain amyloidosis (AL) cardiomyopathy occurs in patients with AL or [...]

436 A peri-myocarditis unmasks an underlying hypertrophic cardiomyopathy

Abstract Methods and results A 41-year-old black man complaining of severe oppressive chest pain radiated to the back presented to our accident & emergency department (A&E). His symptoms started few days before his hospital admission. Past medical history was remarkable for arterial hypertension in medical therapy and microdrepanocytosis. In A&E, the patient’s physical examination and vital signs were normal, he was normotensive, apyretic with normal oxygen saturation. The ECG showed ST elevation in anterior and lateral leads. Because of his history of arterial hypertension, and the severe chest pain irradiated to the back, an angio-CT was indicated at first. The CT ruled out acute aortic disease. Excluded the acute aortic disease, the patient underwent an urgent coronary angiography. No coronary stenosis was found. Therefore, the patient was admitted in cardiac intensive care unit. The blood test showed an elevation of high sensitive cardiac troponin T (cTnT peak 3093 ng/L) and inflammatory index (leukocytosis 13.65 109/l and protein C reactive peak 347 mg/L). An in-depth anamnestic collection revealed fever with respiratory symptoms about 2 weeks before. The echocardiography demonstrated left ventricular (LV) dysfunction with increased ventricular wall thickness and mild pericardial effusion. No LV outflow tract obstruction was found. A provisional diagnosis of peri-myocarditis was made. During hospitalization, anti-remodelling cardiac therapy was introduced and up titrated. To confirm the provisional diagnosis, a Gadolinium cardiac Magnetic Resonance (CMR) was performed, and it revealed myocardial oedema on basal anterior interventricular septum and multiple areas of late gadolinium enhancement with subepicardial pattern. Moreover, severe LV hypertrophy was confirmed (interventricular septum 19 mm, inferior wall 17 mm). This pattern was consistent to the diagnosis of peri-myocarditis on a hypertrophic cardiomyopathy (HCM). Main infectious causes of peri-myocarditis were investigated, but the results were inconclusive. Unfortunately, genetic test results are still not available. Patient was discharged with recovered LV systolic function and free of symptoms on optimal medical therapy; no ventricular arrhythmias was detected during hospitalization. HCM risk sudden cardiac death (SCD) was lower than 4%. Conclusions Peri-myocarditis can mimic symptoms of an acute coronary syndrome. Furthermore, the inflammation of cardiac muscle and the subsequent interstitial oedema may cause an increase in LV wall thickness. In this setting, the diagnosis of an underlying cardiomyopathy is challenging. This interesting and unusual case highlights the relevance of an accurate diagnostic work up to deliver good clinical practice. In particular, Gadolinium CMR is of paramount importance in this setting.

Electrocardiogram Criteria to Diagnose Cardiac Amyloidosis in Men With a Bundle Branch Block

Diagnosing cardiac amyloidosis is challenging and requires a high index of suspicion in patients with an increased left ventricular wall thickness (LVWT). Low QRS voltage on electrocardiogram (ECG) has been regarded as the hallmark ECG finding in cardiac amyloidosis; however, the presence of low voltage can range from 20-74% and the voltage/mass ratio carries a greater diagnostic accuracy than QRS voltage alone. Patients with cardiac amyloidosis can have conduction system infiltration and this may result in a BBB. Therefore, the ECG or mass/voltage criteria established for patients with a narrow QRS in the diagnosis of cardiac amyloidosis may not be applicable in patients with a BBB. We sought to identify criteria to aid in the diagnosis of cardiac amyloidosis in patients with increased LVWT on echocardiogram and with a BBB on ECG. We calculated the total QRS score/LVWT, limb lead QRS score/LVWT, R in lead aVL/LVWT, R in lead I/LVWT, and Sokolow index/LVWT. In patients with an increase in LVWT and BBB, total QRS voltage that is indexed to wall thickness can help distinguish between patients with increased wall thickness who have cardiac amyloidosis from those who have LVH related to a pressure overload state. A unique index of Total QRS Score/LVWT is the best predictor of cardiac amyloidosis with a cutoff value of 92.5 mV/cm which is 100% sensitive and 83% specific for the diagnosis of cardiac amyloidosis. This may be a useful screening tool in patients with an increased wall thickness to raise diagnostic suspicion for cardiac amyloidosis.

Cardiac Structure and Function in Elite Female and Male Soccer Players

Population-specific normative data are essential for the evaluation of competitive athletes. At present, there are limited data defining normal electrocardiographic (ECG) and echocardiographic values among elite US soccer players. To describe ECG and echocardiographic findings in healthy elite US soccer players. This cross-sectional study analyzed Fédération Internationale de Football Association-mandated screening sessions performed at US Soccer National Team training locations from January 2015 to December 2019. US women's and men's national team soccer players undergoing mandated cardiovascular screening were included. Normal training-related and abnormal ECG findings were reported using the International Recommendations for Electrocardiographic Interpretation in Athletes. Echocardiographic measurements of structural and functional parameters relevant to cardiovascular remodeling were assessed relative to American Society of Echocardiography guideline-defined normal ranges. A total of 238 athletes (122 [51%] female; mean [SD] age, 20 [4] years; age range, 15-40 years) were included. Male athletes demonstrated a higher prevalence of normal training-related ECG findings, while female athletes were more likely to have abnormal ECG patterns (14 [11%] vs 0 in male cohort), largely accounted for by abnormal T-wave inversions. Echocardiography revealed no pathologic findings meeting criteria for sport restriction, but athletes frequently exceeded normal ranges for structural cardiac parameters responsive to exercise-induced remodeling including body surface area-indexed left ventricular (LV) mass (58 of 113 female athletes [51%] and 67 of 114 male athletes [59%]), indexed LV volume (89 of 115 female athletes [77%] and 76 of 111 male athletes [68%]), and LV wall thickness (37 of 122 female athletes [30%] and 47 of 116 male athletes [41%]). Age-stratified analysis revealed age-dependent increases in LV wall thickness, mass, and volumes among female athletes and LV wall thickness and mass among male athletes. These data represent the first set of comprehensive normative values for elite US soccer players and one of the largest sport-specific echocardiographic remodeling studies in female athletes. Abnormal ECG findings were more common in female athletes, while both female and male athletes frequently exceeded clinical normality cut points for remodeling-associated echocardiographic parameters.

Abstract 16416: Associations of NT-proBNP and High Sensitivity Cardiac Troponin T Concentrations With 6-year Changes in Left Ventricular Structure and Function in Older Adults: The Atherosclerosis Risk in Community (ARIC) Study

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) improve prediction of incident heart failure (HF) and are cross-sectionally associated with left ventricular (LV) remodeling, but their associations with changes in cardiac structure and function are unclear. Hypothesis: Concentrations of NT-proBNP and hs-cTnT associate with 6-year change in cardiac structure in older adults. Methods: We studied 1,916 participants aged 67-88 in the ARIC Study free of overt cardiovascular disease at baseline (study Visit 5; 2011-13). We quantified the associations of baseline NT-proBNP and hs-cTnT with subsequent changes in LV structure and systolic and diastolic function assessed by echocardiography over a median of 6.6 (IQR 6.1-7.0) years using multivariable linear regression and restricted cubic spline models. Models adjusted for demographics, systolic blood pressure, heart rate, body mass index, diabetes, hypertension, kidney function, and the baseline echocardiographic value of interest at Visit 5. Results: Mean age was 75±4 years, 60% were female, 23% were black, median hs-cTnT was 9 (IQR 6-13) ng/L and NT-proBNP was 88 (50-157) ng/L at Visit 5. In adjusted models, higher hs-cTnT was modestly associated with 6-year increase in LV wall thickness (p=0.02) but not with changes in LV function. In contrast, higher NT-proBNP at Visit 5 was associated with 6-year increase in LV mass, decline in LV systolic function (ejection fraction, longitudinal and circumferential strain), and worsening of diastolic function (left atrium volume, E/e’, tricuspid regurgitation peak velocity) (all p<0.01, Figure ). These associations were non-linear. Conclusions: Higher NT-proBNP, but not hs-cTnT, concentrations are associated with greater declines in LV systolic and diastolic function over ~6 years in late life.

MISOPROSTOL ATTENUATES CARDIOMYOCYTE PROLIFERATION IN THE NEONATAL HEART THROUGH A BNIP3-DELTA-EXON3/MEF2-DEPENDENT SIGNALLING PATHWAY

Systemic hypoxia resulting from preterm birth, placental abnormalities, and cyanotic congenital heart disease is known to impede the regulatory and developmental pathways in the neonatal heart. While the molecular mechanisms are still unknown, stressors that result from systemic hypoxia drive aberrant cardiomyocyte proliferation, which may be initially adaptive, but ultimately can program the heart to fail in early life. Recent evidence has suggested that the prostaglandin E1 analogue, Misoprostol, is cytoprotective in the hypoxia-exposed neonatal heart through promoting the expression of the BCL-2/adenovirus E1B 19 kd-interacting protein 3 (Bnip3) isoform lacking the third exon (Bnip3-Delta-Exon3). Using a rodent model of neonatal hypoxia, in combination with rat primary ventricular neonatal cardiomyocytes (PVNC’s) and H9c2 cells, we sought to determine if Misoprostol can prevent cardiomyocyte proliferation and what the key molecular players may be in this pathway. At post-natal day (PND) 5, hypoxia-exposed rat pups demonstrated elevated heart weights, while histological analysis confirmed, significant increases in left-ventricular wall thickness in the absence of fibrosis (P < 0.05) and increased nuclei number (P < 0.05), which was completely attenuated with the addition of 10 μg/kg/day Misoprostol. Concurrently, molecular markers of proliferation, including Cyclin-D1 were significantly elevated in hypoxia-exposed hearts and cells, which was also prevented in the presence of Misoprostol (P < 0.05). We further describe a critical role for Bnip3-Delta-Exon3 in the regulation of cardiomyocyte proliferation at the transcriptional level, where this isoform reduced the expression of myocardin, while favoring expression of the cardiac maturation factors, BMP-2 and MEF2A over their proliferative counterparts, BMP-10 and MEF2C. These observations were further supported with knockdown studies in H9c2 cells, where we are able to restore hypoxia-induced cardiomyocyte proliferation in Misoprostol-treated cells with the addition of an siRNA targeting Bnip3-Delta-Exon3. Taken together this data demonstrates a clear mechanism for hypoxia-induced neonatal cardiomyocyte proliferation which can ultimately be reversed pharmacologically with the addition of exogenous PGE1 signaling, through Misoprostol.

Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults.

Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Impact of obesity on longitudinal changes to cardiac structure and function in patients with Type 2 diabetes mellitus.

Few prospective studies have evaluated the natural progression of left ventricular (LV) remodelling in patients with Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the impact of obesity on longitudinal cardiac structural and functional changes in patients with T2DM. This study comprised of 274 patients with T2DM (mean age, 62.2 ± 11.4 years; male, 51.5%). Echocardiographic parameters including LV geometry, systolic, and diastolic functions were measured at baseline and follow-up. The median follow-up was 24 months (from 12 months to 48 months). The entire cohort showed a significant increase in LV wall thickness, LV mass (LVM), and prevalence of concentric hypertrophy (19.6-27.3%). Further, systolic function and diastolic function had deteriorated at follow-up assessment. Multivariable adjusted linear regression demonstrated that baseline body mass index (BMI) predicted longitudinal change to LVM (β = 0.29, P < 0.01) and LV ejection fraction (β = -0.15, P < 0.05). Patients were divided into three groups according to their BMI: normal weight (BMI <23 kg/m2), overweight (BMI between 23 kg/m2 and 27.5 kg/m2), or obese (BMI ≥27.5 kg/m2). Importantly, obesity at baseline predicted a greater longitudinal increase in LVM and decrease in LV ejection fraction compared with overweight and normal weight patients. Being obese at baseline was associated with greater longitudinal increase in LV mass and greater deterioration in LV systolic function.

Can the echocardiographic LV mass equation reliably demonstrate stable LV mass following acute change in LV load?

Limited data are available on performance of the left ventricular (LV) mass equation when there is a dynamic change to LV load. We aimed to test this equation in the immediate post-operative period following aortic valve replacement (AVR) for aortic regurgitation (AR) to see if it would reliably demonstrate stable LV mass before and after surgery. Since LV mass would be unlikely to change in the immediate postoperative period, we hypothesized that a decrease in LV diameter postoperatively would be accompanied by concomitant increases in LV wall thickness as predicted by the LV mass equation. We reviewed echocardiograms of adult patients with AR who underwent AVR from 2007-2017 at Montefiore Medical Center (n=28). Three independent readers performed septal wall thickness (SWT), posterior wall thickness (PWT) and left ventricular internal diameter (LVID) measurements on pre-operative and post-operative echocardiograms. LV masses were calculated using the American Society of Echocardiography (ASE) equation. Post-operatively, LVID decreased from 5.7±1.2 to 4.9±1.0 cm, P<0.001. SWT was noted to increase from 1.08±0.20 to 1.18±0.27 cm, P=0.03, but PWT was unchanged, 1.11±0.21 to 1.16±0.27 cm, P=0.21. Accordingly, the LV mass equation calculated a decrease in LV mass from 266±126 to 232±99 gm, P=0.01. A control group of coronary artery bypass grafting alone (n=14) did not demonstrate any significant change in SWT, LVID, PWT and LV mass measurements. Similar findings were found for all three readers. Following aortic valve replacement for regurgitation, the LV mass equation calculated a reduction in LV mass in the immediate postoperative period. Since an immediate change in LV mass after AVR is unlikely, we feel that these results highlight an important limitation of the mass equation, when used with acutely changing loading conditions.

Electrocardiographic and echocardiographic specificities of young mixed-race athletes from Reunion Island

Electrocardiographic (ECG) and echocardiographic (ETT) characteristics of Afro-Caribbean athletes changed recommendations in sports cardiology. No specific data has been provided for mixed-race athletes so far. To compare ECG and ETT characteristics of adolescent mixed-race (M) athletes with those of Caucasian (C) and African (A) athletes. Between 12/2015 and 08/2017, 100 young athletes born in Reunion Island (70M, 18C, 12A) were included in our study. ECG and ETT were performed during a pre-participation screening before competitive sporting activity. M athletes showed no ECG specificity. The ‘Afro-Caribbean athletes’ repolarization’ was found in 5.7% of M athletes. M and A athletes demonstrated a greater wall thickening induced by exercise compared to C athletes [IVSd indexed at 5.2 ± 0.6 mm/m 2 and 5.3 ± 0.6 mm/m 2 ( P M/A = 0.363) versus 4.8 ± 0.6 mm/m 2 respectively ( P M/C = 0.011, P A/C = 0.024)]. M and C athletes featured larger left-ventricular cavity size compared to A athletes [LVIDd indexed at 28.8 ± 2.9 mm/m 2 and 28.9 ± 2.4 mm/m 2 ( P M/C = 0.887) versus 26.4 ± 2.5 mm/m 2 respectively ( P M/A = 0.011, P C/A = 0.013)]. Morphologic Left-Ventricular (LV) remodeling in mixed-race adolescent athletes is characterized by a greater LV cavity enlargement compared to A athletes and a significant increase in LV wall thickness compared to C athletes. ‘Afro-Caribbean repolarization’ is occasionally seen among these athletes.

Annexin A5 reduces infarct size and improves cardiac function after myocardial ischemia-reperfusion injury by suppression of the cardiac inflammatory response

Annexin A5 (AnxA5) is known to have anti-inflammatory and anti-apoptotic properties. Inflammation and apoptosis are key processes in post-ischemic cardiac remodeling. In this study, we investigated the effect of AnxA5 on left ventricular (LV) function and remodeling three weeks after myocardial ischemia-reperfusion (MI-R) injury in hypercholesterolemic ApoE*3-Leiden mice. Using a mouse model for MI-R injury, we demonstrate AnxA5 treatment resulted in a 27% reduction of contrast-enhanced MRI assessed infarct size (IS). End-diastolic and end-systolic volumes were decreased by 22% and 38%, respectively. LV ejection fraction was increased by 29% in the AnxA5 group compared to vehicle. Following AnxA5 treatment LV fibrous content after three weeks was reduced by 42%, which was accompanied by an increase in LV wall thickness of the infarcted area by 17%. Two days and three weeks after MI-R injury the number of cardiac macrophages was significantly reduced in both the infarct area and border zones following AnxA5 treatment compared to vehicle treatment. Finally, we found that AnxA5 stimulation leads to a reduction of IL-6 production in bone-marrow derived macrophages in vitro. AnxA5 treatment attenuates the post-ischemic inflammatory response and ameliorates LV remodeling which improves cardiac function three weeks after MI-R injury in hypercholesterolemic ApoE*3-Leiden mice.

Oxidative stress impairs myocyte autophagy, resulting in myocyte hypertrophy.

What is the central question of this study? Does oxidative stress induce impairment of autophagy that results in myocyte hypertrophy early after pressure overload? What is the main finding and its importance? In cultured myocytes, hydrogen peroxide decreased autophagy and increased hypertrophy, and inhibition of autophagy enhanced myocyte hypertrophy. In rats with early myocardial hypertrophy after pressure overload, myocyte autophagy was progressively decreased. The antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol prevented the decrease of myocyte autophagy and attenuated myocyte hypertrophy early after pressure overload. These findings suggest that oxidative stress impairs myocyte autophagy that results in myocyte hypertrophy. Insufficient or excessive myocyte autophagy is associated with left ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy in vitro and pressure overload-induced LV hypertrophy in vivo. In the present study, we tested the hypothesis that oxidative stress induces an impairment of autophagy that results in myocyte hypertrophy. H9C2 cardiomyocytes pretreated with the autophagy inhibitor 3-methyladenine were exposed to 10 and 50μm hydrogen peroxide (H2 O2 ) for 48h. Male Sprague-Dawley rats underwent abdominal aortic constriction (AAC) or sham operation. The animals were killed 24, 48 or 72h after surgery. In a separate group, the AAC and sham-operated rats randomly received the antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol for 72h. In H9C2 cardiomyocytes, H2 O2 decreased the ratio of microtubule-associated protein light chain 3 (LC3) II to LC3 I and increased P62 and phosphorylated ERK (p-ERK) proteins and myocyte surface area. 3-Methyladenine further increased H2 O2 -induced p-ERK expression. In rats after AAC, the heart to body weight ratio was progressively increased, the LC3 II/I ratio was progressively decreased, p62 and p-ERK expression was increased, and expression of Beclin1, Atg5 and Atg12 was decreased. N-Acetyl-cysteine or tempol prevented the decreases in the LC3 II/I ratio and Beclin1 and Atg5 expression and attenuated the increases in LV wall thickness, myocyte diameter and brain natriuretic peptide expression in AAC rats. In conclusion, oxidative stress decreases Beclin1 and Atg5 expression that results in impairment of autophagy, leading to myocyte hypertrophy. These findings suggest that antioxidants or restoration of autophagy might be of value in the prevention of early myocardial hypertrophy after pressure overload.

LEFT VENTRICULAR REMODELING IN YOUNG BLACK ATHLETES

BackgroundEKG analysis investigating the impact of the ethnicity on cardiac adaptation to exercise has shown a higher presence of abnormalities, including marked repolarization changes, and signs of left ventricular (LV)...

Effect of Sex and Sporting Discipline on LV Adaptation to Exercise

ObjectivesThis study sought to investigate the effect of different types of exercise on left ventricular (LV) geometry in a large group of female and male athletes. BackgroundStudies assessing cardiac adaptation in female and male athletes indicate that female athletes reveal smaller increases in LV wall thickness and cavity size compared with male athletes. However, data on sex-specific changes in LV geometry in athletes are scarce. MethodsA total of 1,083 healthy, elite, white athletes (41% female; mean age 21.8 ± 5.7 years) assessed with electrocardiogram and echocardiogram were considered. LV geometry was classified into 4 groups according to relative wall thickness (RWT) and left ventricular mass (LVM) as per European and American Society of Echocardiography guidelines: normal (normal LVM/normal RWT), concentric hypertrophy (increased LVM/increased RWT), eccentric hypertrophy (increased LVM/normal RWT), and concentric remodeling (normal LVM/increased RWT). ResultsAthletes were engaged in 40 different sporting disciplines with similar participation rates with respect to the type of exercise between females and males. Females exhibited lower LVM (83 ± 17 g/m2 vs. 101 ± 21 g/m2; p < 0.001) and RWT (0.35 ± 0.05 vs. 0.36 ± 0.05; p < 0.001) compared with male athletes. Females also demonstrated lower absolute LV dimensions (49 ± 4 mm vs. 54 ± 5 mm; p < 0.001) but following correction for body surface area, the indexed LV dimensions were greater in females (28.6 ± 2.7 mm/m2 vs. 27.2 ± 2.7 mm/m2; p < 0.001). Most athletes showed normal LV geometry. A greater proportion of females competing in dynamic sport exhibited eccentric hypertrophy compared with males (22% vs. 14%; p < 0.001). In this subgroup only 4% of females compared with 15% of males demonstrated concentric hypertrophy/remodeling (p < 0.001). ConclusionsHighly trained athletes generally show normal LV geometry; however, female athletes participating in dynamic sport often exhibit eccentric hypertrophy. Although concentric remodeling or hypertrophy in male athletes engaged in dynamic sport is relatively common, it is rare in female athletes and may be a marker of disease in a symptomatic athlete.

OP.8A.01] EXERCISE-INDUCED HYPERTENSION AND CARDIAC HYPERTROPHY IN EPINEPHRINE-DEFICIENT MICE

Objective: Phenylethanolamine-N-methyltransferase (Pnmt) is required for the conversion of norepinephrine to epinephrine. Bao et al (2007) described that Pnmt-knockout (Pnmt-KO) mice have an increased ratio of left ventricular (LV) posterior wall thickness to internal dimensions (LVPW/LVID) but not overall cardiac hypertrophy. Pnmt-KO mice showed normal resting blood pressure (BP) but became hypertensive during treadmill exercise. The aim of this study was to evaluate cardiac morphological and functional alterations after chronic exercise in Pnmt-KO mice. Design and method: PCR-based genotyping was performed at the Pnmt locus of 10-week-old Pnmt-KO (Pnmt-/-) and WT mice (129x1/SvJ). Epinephrine and norepinephrine were quantified by RP-HPLC-ED in adrenal glands. Animals were submitted to a 6-week exercise training program. BP was measured by a photoelectric pulse detector. Mice were anesthetized (sevoflurane, 8%) and cardiac morphology and function were evaluated by echocardiography followed by morphometric analysis. Results: Epinephrine levels were vestigial in Pnmt-KO compared with WT mice. There were no differences in systolic and diastolic BP between untrained Pnmt-KO and WT mice. However, trained Pnmt-KO mice showed a significant increase in systolic BP when compared to trained WT mice. Our findings also showed that the ratios between heart weight (HW/BW) and LV weight (LVW/BW) and body weight (BW) were significantly increased in trained compared to untrained Pnmt-KO mice. Trained Pnmt-KO mice presented higher HW/BW than trained WT mice. Untrained Pnmt-KO mice display echocardiographic results similar to those reported by Bao et al (2007) while LVPW and IVS thicknesses, LV end-diastolic internal dimension (LVIDd) and LV mass indexed for body surface area (LVMi) were significantly increased in trained Pnmt-KO mice, indicating overall LV hypertrophic changes. Indexed LV end-diastolic volume (LVEDVi), indexed stroke volume (SVi) and cardiac index (CI) were significantly higher in trained Pnmt-KO than untrained Pnmt-KO mice. Conclusions: In conclusion, the increased BP in Pnmt-KO mice in response to exercise appears to be associated with an increase in LV wall thickness and chamber volume suggesting hypertrophic remodelling of the LV in Pnmt-KO mice. Epinephrine appears to be essential for maintaining normal BP, probably through β2-adrenoceptors-induced vessel relaxation, and preventing LV hypertrophy in chronic exercise.

OP.4B.04] LONGITUDINAL CHANGES IN LEFT VENTRICULAR STRUCTURE AND DIASTOLIC FUNCTION IN RELATION TO ARTERIAL PROPERTIES IN A GENERAL POPULATION

Objective: Serial imaging studies are needed to clarify the relation of change in left ventricular (LV) structure and function with arterial stiffness. In this longitudinal population study, we assessed in continuous and categorical analyses to what extent arterial properties predict alterations in echocardiographic indexes reflecting LV structure and function. Design and method: In 607 participants (50.7% women; mean age, 50.7 years), using conventional echocardiography and tissue Doppler imaging, we measured LV dimensions, transmitral blood flow and mitral annular tissue Doppler velocities at baseline and after 4.7 years. Using applanation tonometry, we assessed augmentation pressure (AP), central pulse pressure (cPP) and carotid-femoral pulse wave velocity (PWV) at baseline. Standardized effect size was expressed as percent of changes in standard deviation (SD) of δ echocardiographic indexes associated with 1-SD increase in baseline arterial indexes. Results: The clinical correlates of δLV indexes included baseline LV index, age, sex, body mass index, mean blood pressure, pulse rate and changes over time in these co-variables. After full adjustment, longitudinal increase in LV septal (standardized effect size: +14.6%; P = 0.0017) and posterior wall (+13.3%; P = 0.0015) thickness was significantly associated with higher PWV at baseline, whereas LV internal diameter (−12.2%; P = 0.014) decreased with PWV. Consequently, a greater increase in relative wall thickness was associated with baseline PWV (+17.2%; P < 0.0001). We observed similar longitudinal increase in LV wall thickness in relation to higher baseline PWV in men and women. In adjusted logistic analysis, higher baseline PWV was associated with a 156% increase in the odds of developing LV concentric remodeling during follow-up as compared to participants who improved LV geometry (P = 0.0088). Furthermore, in women, a higher baseline cPP predicted a greater increase in LV mass (+18.1%, P = 0.018) and E/e’ ratio (+25.8%, P = 0.0064). Conclusions: The key finding of this study is that longitudinal increase in LV relative wall thickness was associated with higher baseline PWV, measure of arterial stiffness. Moreover, in women, a higher cPP predicted worsening of LV diastolic function. Our study demonstrated the importance of arterial properties as a mediator of LV concentric remodeling in men and women, and diastolic dysfunction in women.

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

Native T1 values in discrimination of subclinical profibrotic phenotype in relatives of patients with hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) is associated with significant associated morbidity and mortality. Increased maximal left ventricular wall thickness (LVWT) has been postulated as major risk factor of sudden death; however, relatives with normal LVWT are also at risk. Genetically driven interstitial collagenesis has been proposed as a possible mechanism of diffuse myocardial fibrosis and increased extracellular volume fractions (ECV) has been demonstrated in genotype positive subjects. We investigated whether native T1 can also separate genotype positive subjects in the absence of increase in LVWT and how does it relate to ECV measurements.

Adverse cardiac remodeling due to maternal low protein diet is associated with alterations in expression of genes regulating glucose metabolism

Background and aimsWe have previously shown that a maternal low protein (LP) diet during pregnancy in the rat results in adverse ventricular remodeling and contractile deficiencies of the neonatal rat heart. Since pathological cardiac hypertrophy is associated with increased expression of genes involved in glucose handling, this study was undertaken to examine if maternal LP diet alters the expression of genes encoding for some key components of glucose metabolism and uptake, and of the insulin receptor (IR) signal transduction in the heart of male offspring. Methods and resultsWe determined the effect of maternal LP and normal diet (90 and 180 g/casein/kg respectively) on IR β-subunit, insulin receptor substrate (IRS)-1, phosphotyrosyl protein phosphatase (PTP) 1B, GLUT4 and phosphatidylinositol (PI) 3-kinase in male rat offspring at 24 h and at 1, 4 and 8 wks post-partum. Quantitative real-time RT-PCR revealed significant age-dependent increases in the expression of IR β-subunit, IRS-1, PTP1B, GLUT4 and PI3-kinase in the LP group with concomitant increases in corresponding protein abundance at 4 wks of age. These changes were associated with increases in left ventricular (LV) internal diameters as well as increases in LV wall thickness. ConclusionA maternal LP diet can induce increases in the gene expression and protein levels of key components of glucose metabolism and the IR signal transduction pathway in the neonatal rat heart, which may be related to accelerated energy supply, demand and utilization for ventricular remodeling due to compromised contractile performance during early life.