Mean Left Ventricular Wall Thickness Research Articles

Left Atrium Enlargement Is An Independent Predictor of Overall Mortality In Patients with Cardiac AL Amyloidosis.

AbstractAbstract 4621 Background:Primary systemic amyloidosis (AL) is a severe plasma cell disorder characterized by amyloid fibrils extracellular deposition in different organs. Myocardial involvement is frequent and has major impact on prognosis. Echocardiography (TTE) is the most common test performed when cardiac involvement is suspected. We hypothesized that a simple measurement of left atrium enlargement (LA) by TTE may provide an important risk marker for this disease. Methods and results:Between 1997 and 2010, 114 patients were diagnosed with systemic AL. Sixty one patients of the cohort (54%) had cardiac involvement on the basis of standard criteria defined as: mean LV wall thickness >12mm with no other cardiac causes. They had first TTE within 16 days of diagnosis. Patients were mainly treated with conventional chemotherapy (M-Dex) or with new agents for refractory or relapsing patients We retrospectively collected demographic baseline characteristics along with biological and echo data of these patients. Mean age was 61±11 years; 60% were male; 19% had hypertension. Mean left ventricular ejection fraction and mean LV wall thickness were respectively 58±13% and 15±3 mm. Mean follow up time was 2.1±2 years. None had significant valvular heart disease. LA enlargement was defined by M mode as > 40 mm in male and > 36 mm in female. Patients with enlarged LA had significantly more hypertension and lower ejection fraction and more hypertrophied LV walls (All P< 0.05). At 3 years, survival rate was markedly reduced in patients with enlarged LA vs. those with normal LA: 34±9% vs.75 ±9% (P =0.02). By multivariate analysis, after adjusting for age, gender, and presence of hypertension, LA enlargement remained an independent predictor of overall mortality at 3 years (HR=2.88; CI (1.12-8.84); P=0.03). Conclusion:In patients with systemic AL amyloidosis and cardiac involvement, LA enlargement, a surrogate marker of diastolic dysfunction and elevated LV filling pressure, is a powerful independent predictor of long-term mortality. Therefore LA enlargement may help to enhance risk stratification in patients presenting with this disease. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy

Hypertrophic cardiomyopathy (HCM) affects most infants with Pompe disease (PD), and may serve as a marker for its antenatal diagnosis (ANDx) by fetal echocardiography (FE). Fetuses diagnosed with HCM between 2006 and 2009 were included in this study. HCM, defined as Z-score of mean left ventricular wall thickness (LVWT) and/or mass (LVM) above 2, was detected in 5/1,268 fetuses (0.39%) carried by 1,137 pregnant women referred for FE. Three fetuses (0.24%) had postnatal confirmation of PD. Their gestational age and fetal weight at diagnosis was (mean ± standard deviation) 31 ± 3.6 weeks and 1.9 ± 0.2 kg, respectively. Fetal Z-score of LVM and LVWT was 3.8 ± 0.9 and 3.1 ± 0.6, respectively. Postnatally, acid α-glucosidase (GAA) enzyme activity was nearly absent in all patients, 2 were homozygous for the mutation 1327-2A>G in the GAA gene, and 1 was homozygous for 340insT. Enzyme replacement therapy (ERT) was initiated 4.9 ± 7.8 days after birth (range 2 h-14 days), and continued every 2 weeks. Two infants are alive at 4 and 31 months, and one died of aspiration pneumonia at 19 months. Cardiac hypertrophy resolved after 10-12 weeks of ERT in all patients, and none required any respiratory support. One patient had normal neurodevelopmental assessment at 25 months, and one had severe global delay at 15 months before death. ANDx of PD by FE is feasible based on fetal HCM. It promotes early initiation of ERT which may improve outcome in some patients. However, larger studies and longer follow-ups are required.

059 Relationship between exercise related blood pressure response and differences in magnitude of left ventricular hypertrophy between African/Afro-Caribbean (black) athletes and Caucasian athletes: Abstract 59 Table 1

Purpose Participation in regular physical exercise is associated with a greater magnitude of left ventricular hypertrophy in male athletes of African/Afro-Caribbean origin (black athletes) compared with athletes of Caucasian origin of similar age and size, participating in similar exercise disciplines. The precise genetic, biochemical and physiological mechanisms for these differences is unknown. However, the role of exercise related blood pressure response as a determinant of exercise induced left ventricular hypertrophy has not been investigated. Aim The study sought to investigate whether there were differences in exercise related blood pressure response in black athletes and Caucasian athletes. Method Between 2004 and 2007, 300 black athletes and 300 whites athletes (mean age 20±5 years) participating at regional or national level underwent echocardiographic evaluation. Of these 54 black athletes (18%) and 12 white athletes (4%) exhibited a LV wall thickness >12 mm indicating LVH. Black and Caucasian athletes with left ventricular hypertrophy of >12 mm were subject to exercise stress testing with simultaneous blood pressure recording using the Bruce protocol. All athletes were exercised to the point of volitional exhaustion. Results Black athletes exhibited a greater mean left ventricular wall thickness compared with white athletes (11.3±1 mm; range 13–16 mm v. 10±1.5 mm; range 13–14 mm: p<0.0001). The blood pressure responses to exercise are tabulated below ([Abstract 59 Table 1][1]). There were no significant differences in blood pressure response to exercise between black athletes and white athletes. View this table: Abstract 59 Table 1 Shows the comparison in mean systolic BP response to different stages of the Bruce stress test in black athletes and white athletes Conclusion The greater magnitude of left ventricular hypertrophy in blacks is not explained by a difference in exercise related blood pressure response. [1]: #T1

Early Detection of Cardiac Systolic Functional Impairment and Correlation with NT-ProBNP Change in AL Amyloidosis by Cardiac Lateral Wall Tissue Doppler S Wave.

Abstract 2814Poster Board II-790N-terminal fragment of brain natriuretic peptide is a cardiac biomarker that has prognostic significance in amyloidosis and NT-ProBNP can rapidly change after completion of chemotherapy. We and others who have previously reported such changes in NT-ProBNP to be of prognostic significance but there was no cardiac “progression” or “improvement” according to the international amyloidosis consensus criteria (Gertz et al 2005) in the majority - making this finding difficult to explain. We now report subtle changes in left ventricular systolic function using lateral wall tissue Doppler as a new robust and reproducible parameter correlating well with such changes in NT-ProBNP.Patients with cardiac amyloidosis as defined by the international consensus criteria who had good renal function (creatinine clearance >30ml/min), received chemotherapy and had a significant change in NT-ProBNP after chemotherapy were identified from the database of the UK National Amyloidosis Centre. A significant change in NT-ProBNP was defined as minimum rise or fall of 30% over the baseline pre-treatment value.Ninty seven patients with identified. All analysis was repeated on stored off line data on EchoPAC” in accordance with British Society of Echocardiography guidelines with special focus on ejection fraction (EF) (Biplane Simpson's method), longitudinal 2D strain, lateral TDI S wave (Tissue Doppler Imaging) and mean left ventricular wall thickness. At baseline the mean EF was 59%, mean LV wall thickness 13mm and mean TDI S wave velocity 0.07m/sec. 76/97 (78%) patients showed a significant increase in the NT-proBNP levels and 21/97 (22%) showed a significant a decrease. There was a significant correlation between the free light chain (FLC) level and NT-ProBNP at diagnosis (correlation coefficient 0.322; p <0.001). NT-ProBNP decreased from median 444 to 144 pMol/L (p=0.021) among patients who had a complete FLC response. There was also good correlation between the NT-ProBNP level with interventricular septal and left ventricular posterior wall thickness (spearman correlation coefficient 0.55, significance 0.01) at baseline. None of the patients had cardiac progression or improvement by echocardiography according to the international consensus criteria . In both groups of patients (increase or decrease in NT-ProBNP), there was no significant change in the LV wall thickness. In patients with a decrease in the NT-proBNP, there was no significant increase in the ejection fraction or longitudinal 2-D strain in the evaluable cases. But there was a significant improvement in the mean lateral TDI S wave (a marker of longitudinal LV systolic function) from 0.07 m/s to 0.08m/s (p=0.02) suggesting improvement in systolic function. In patients with an increase in the NT-ProBNP, there was a significant decrease in the mean EF from 60% to 56% (p=0.032). The longitudinal 2D strain also decreased significantly by mean of 10% (-13.9% to -12.6%; p=0.009) and the lateral TDI S wave also showed significant worsening with a decline from 0.09m/sec to 0.07m/sec (p <0.001).NT-ProBNP changes after chemotherapy have remained difficult to explain. The international consensus criteria for cardiac progression or improvement by echocardiography - a 2 mm change in the LV wall thickness or 20% change in EF - are relatively insensitive and the clinical criteria (change in NYHA class by 2) are not robust or reproducible to detect cardiac improvement or progression. Lateral TDI S wave is a robust and reproducible parameter that correlates well with both an increase and decrease drop in NT-ProBNP levels. This suggests that there are subtle changes to the left ventricular systolic function which correlate well with change in NT-ProBNP and are of prognostic significance. These changes in systolic function occur well before any substantial diastolic functional change or change in wall thickness. This interesting finding needs further validation in larger groups and if confirmed should be considered for incorporation in the consensus criteria for cardiac progression or improvement. Disclosures:No relevant conflicts of interest to declare.

High-Sensitivity Troponin Assay Improves the Detection of Cardiac Involvement in AL Amyloidosis and Is the Most Powerful Prognostic Determinant.

Abstract 1782Poster Board I-808The heart is involved in approximately two thirds of patients with AL amyloidosis and the prognosis of the disease is largely dependent on the severity of cardiac damage. Heart dysfunction can be assessed by measuring the serum concentrations of N terminal natriuretic peptide type B (NT-proBNP) and of cardiac troponins (cTn). The combination of these biomarkers allows an accurate prognostic stratification of patients with AL amyloidosis. Recently, new generation of more sensitive assays for cTn, characterized by low limits of detection and low imprecision, have been developed, aiming at identifying minimal cardiac damage. We report the impact of a highly sensitive (hs) cTnT assay on detection of heart involvement, prognosis and response to therapy in 109 consecutive newly diagnosed patients with AL amyloidosis.The hs-cTnT was measured on the Modular E instrument with a precommercial immunoassay from Roche Diagnostics on frozen sera collected at the time of diagnosis and stored at -80°C. The 99th centile of hs-cTnT concentration in sera from 546 healthy volunteers is 14 ng/L (95%CI 12.4-24.9 ng/L). NT-proBNP and cTnI were measured with commercially available assays. The upper reference limit of NT-proBNP is 332 ng/L and for cTnI is 40 ng/L. Heart involvement was defined according to the International Society of Amyloidosis consensus criteria as a mean left ventricular wall thickness (mLVW) >12 mm in the absence of other causes.Sixty-nine of the 109 patients (63%) fulfilled the echocardiographic criteria of heart involvement. Among these patients, 74% had elevated cTnI, 96% had high hs-cTnT and 100% had elevated NT-proBNP. Fifteen patients who did not have echocardiographic heart involvement at presentation reached a mLVW >12 mm within 6 months from diagnosis. Among them, cTnI was elevated at presentation in 33% of cases, hs-cTnT in 80% (p=0.01 compared to cTnI) and NT-proBNP in 73%, indicating that hs-cTnT and NT-proBNP can detect amyloid cardiac involvement when it is still unapparent by conventional echocardiographic criteria. Thirty-seven (34%) patients died and the median follow-up of living patients was 38 months (range 14-67 months). Survival was reduced in patients with hs-cTnT >14 ng/L (58% vs. 84% surviving at 3 years, p=0.01) and NT-proBNP >332 ng/L (58% vs. 86% surviving at 3 years, p=0.02) and cTnI >40 ng/L (52% vs. 75% surviving at 3 years, p=0.007). At multivariate analysis ln(hs-cTnT) was the only variable significantly associated with survival (HR 1.576, 95%CI 1.048-2.371, p=0.03). All the patients were treated with melphalan-dexamethasone and 66 (60%) reached hematologic response. The hs-cTnT cutoff best predicting survival after treatment was 68 ng/L (45% vs. 80% surviving at 3 years, p=0.0003). This cutoff, in combination with hematologic response to therapy, could differentiate the patient population into 3 groups with significantly different survival. Estimated survival at 3 years was 30% in non responders with hs-cTnT >68 ng/L, 51% in those who obtained either hematologic response or had hs-cTnT <68 ng/L (p=0.05) and 95% in responders with hs-cTnT <68 ng/L (p<0.0001).Cardiac troponin measured with a high-sensitivity assay significantly improved the sensitivity, compared with commercially available troponin assay, for cardiac damage caused by AL amyloidosis and represents now the most powerful prognostic determinant. Patients who obtain hematologic response and a hs-cTnT concentration below the threshold of 68 ng/L enjoy prolonged survival. DisclosuresNo relevant conflicts of interest to declare.

Abstract 5420: Suppression of Aldosterone Mediates Left Ventricular Hypertrophy Regression in Patients With Hypertension

Background . Although high circulating aldosterone levels stimulate myocardial fibrosis and left ventricular hypertrophy (LVH), it is less clear whether suppression of aldosterone is associated with LVH regression in hypertensive patients. Methods. The Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial randomized 465 hypertensive overweight subjects to the direct renin inhibitor aliskiren 300mg, losartan 100mg or the combination and followed patients for 9 months. All patients were treated to standard blood pressure targets. LV mass index (LVMI) and LV wall thickness (LVWT) were assessed by cardiac magnetic resonance. A subset of 135 patients with plasma aldosterone (ALDO) measured at baseline and study end was analyzed. Results. At baseline, ALDO correlated poorly with systolic blood pressure (SBP) (r=0.2, p=0.02), LVMI (r=0.18, p=0.03) and LVWT (r=0.22, p=0.01). Mean blood pressure was 144±13/90±9mmHg, mean LVMI was 75±16 g/m 2 , and mean LVWT was 9.8±2.2mm. ALDO was reduced between baseline and end of the study in the aliskiren [244 (202–294) vs. 198 (161–243) pmol/L, p=0.03] and combination groups [209 (169–257) vs. 164 (138–196) pmol/L, p=0.0029], but not in the losartan group [223 (181–275) vs. 235 (199–278) pmol/L, p=0.63] [geometric means (95%CI)]. Reduction in ALDO was associated with regression of LVWT, even after adjustment for SBP reduction, treatment, baseline ALDO and baseline LVWT (p= 0.041). Conclusion . In hypertensive patients with increased LVWT, regression of LVH was associated with suppression of ALDO, independently of the change in SBP, suggesting that ALDO, a known mediator of LVH, may be a particularly important target for suppression.

Systemic Cardiac Amyloidoses

Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis. We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1+/-0.5 versus 0.9+/-0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events. AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.

Association of angiotensin-converting enzyme activity and polymorphism with echocardiographic measures in familial and nonfamilial hypertrophic cardiomyopathy

Angiotensin-converting enzyme (ACE) activity and polymorphism contribute significantly to the prognosis of patients with cardiomyopathy. The aim of this study was to determine the activity and type of ACE polymorphism in patients with familial and nonfamilial hypertrophic cardiomyopathy (HCM) and to correlate these with echocardiographic measurements (echo-Doppler). We studied 136 patients (76 males) with HCM (69 familial and 67 nonfamilial cases). Mean age was 41 +/- 17 years. DNA was extracted from blood samples for the polymerase chain reaction and the determination of plasma ACE levels. Left ventricular mass, interventricular septum, and wall thickness were measured. Mean left ventricular mass index, interventricular septum and wall thickness in familial and nonfamilial forms were 154 +/- 63 and 174 +/- 57 g/m(2) (P = 0.008), 19 +/- 5 and 21 +/- 5 mm (P = 0.02), and 10 +/- 2 and 12 +/- 3 mm (P = 0.0001), respectively. ACE genotype frequencies were DD = 35%, ID = 52%, and II = 13%. A positive association was observed between serum ACE activity and left ventricular mass index (P = 0.04). Logistic regression showed that ACE activity was twice as high in patients with familial HCM and left ventricular mass index >or=190 g/m(2) compared with the nonfamilial form (P = 0.02). No other correlation was observed between ACE polymorphisms and the degree of myocardial hypertrophy. In conclusion, ACE activity, but not ACE polymorphisms, was associated with the degree of myocardial hypertrophy in the patients with HCM.

Delayed Enhancement on Cardiac Magnetic Resonance and Clinical, Morphological, and Electrocardiographical Features in Hypertrophic Cardiomyopathy

Background The clinical, morphological, and electrocardiographical relevance of delayed enhancement (DE) in cardiac magnetic resonance (CMR) was studied in patients with hypertrophic cardiomyopathy (HCM). Methods and Results A total of 56 patients underwent both gadolinium-enhanced CMR and 12-lead electrocardiogram. The CMR demonstrated DE at the left ventricular (LV) wall in 39 patients. The patients with DE included more cases with dilated phase of HCM, higher New York Heart Association (NYHA) classes and incidence of ventricular tachyarrhythmias (VT), lower LV ejection fraction (LVEF) and mean LV wall thickness (WT), and a larger ratio of maximum to minimum LVWT. The QRS duration was prolonged and the QRS axis deviated toward left with increases in the DE volume (r = 0.58 and r = 0.41, P < .01). Abnormal Q waves were present in 5 patients and the location coincided with the DE segments in 4 patients, but the concordance was not significant. The amplitude of T waves correlated with the ratio of the apex to basal LVWT (r = 0.38, P < .01) and was more negative in cases with DE at the apex. Conclusions In HCM, the DE was associated with higher NYHA classes and prevalence of VT, impaired global LV function and asymmetrical hypertrophy, and conduction disturbance, abnormal Q waves, and giant negative T waves.

Abstract 314: Inactivation-Resistant GSK3αβ Dual Isoform Expression Attenuates Isoproterenol-Induced Myocardial Hypertrophy and Preserves Cardiac Function

Glycogen synthase kinase-3 (GSK-3) is implicated as an important signalling mediator in normal developmental myocardial growth and adverse hypertrophic remodelling. Upstream phosphorylation of isoform specific N-terminal serine residues - ser21(GSK-3α) and ser9(GSK-3β), respectively - inhibits kinase activity. Opposing effects of the two isoforms have recently been described in response to hypertrophic stimuli, but little is known of the overall effect of dual-isoform manipulation. We set out to characterise baseline and isoproterenol (ISO) stimulated phenotypes of mice with inactivation-resistant GSK-3αβ knockin (KI) alleles, in which ser21/9 are converted to non-phosphorylatable alanine. Between 5–15 weeks there was a non-significant trend towards higher heart weight (HW): body weight (BW) ratios in KI mice versus wild type (WT) mice. Mean left ventricular wall thickness (LVWT) at the level of the papillary muscle was comparable between genotypes (1.3±0.2mm vs 1.6±0.2mm, ns, n=8). 8–10 week old weight-matched mice received 2 weeks subcutaneous ISO (30mg/kg/d) or control saline (Con) infusions. WT hearts hypertrophied with ISO (LVWT 1.9±0.1mm vs 1.3±0.2mm Con, n=8; HW:BW ratio 6.7±0.6 vs 5.4±0.4 Con, n=10, both p&lt; 0.05), but KI mice did not (1.4±0.1mm vs 1.6±0.2mm KI Con; HW:BW 6.2±1.0 vs 6.1±0.6 KI Con, respectively, both ns). Hypertrophy in the WT hearts was associated with reduced LV ejection fraction (41±9% vs 63±5% Con, n=6, p&lt; 0.05) and greater interstitial fibrosis (2.1±0.5% vs 0.8±0.6%, n=6, p&lt; 0.05). These were both attenuated in the KI mice subjected to ISO (70±13% vs 64±11% Con, and 1.3±0.7% vs 0.8±0.3% Con, respectively, both ns). GSK-3 inhibition with daily intraperitoneal 6-bromoindirubin-3′-oxime restored hypertrophic sensitivity to ISO in the KI mice (LVWT 1.8±0.2mm; HW:BW 7.3±0.5, p&lt; 0.05 for both groups vs KI + ISO alone) but had no effect in the absence of hypertrophic stimulus (1.4±0.2mm and 5.4±0.7, respectively, for KI + Con + Bio, ns vs KI + Con alone). In conclusion, inactivation-resistant GSK-3αβ dual isoform expression does not affect age-related (eutrophic) myocardial growth in the mouse. However, it protects against pathological growth, maintaining cardiac function and attenuating interstitial fibrosis.

Long-Term Assessment of Electrocardiographic and Echocardiographic Findings in Norwegian Elite Endurance Athletes

Objectives: The long-term outcome and clinical significance of athlete’s heart has been debated and more longitudinal data are needed. We present a prospective 15 years’ follow-up study of ECG and echo findings in elite endurance athletes following the end of their competitive career. Methods: Clinical evaluation, ECG, ambulatory Holter recording and echocardiography were performed in 30 top-level endurance athletes with a mean age of 24 years with follow-up 15 years later. All had then ended their competitive career, but still performed recreational sports activities. Results: No clinical events were reported. Average resting heart rate was unchanged (53.5 ± 10 at baseline and 55.4 ± 11 at follow-up, p = n.s.), complex ventricular arrhythmias did not occur and the number of ventricular premature beats (VPBs) were 0.4 ± 0.8/h at baseline and 3.8 ± 10/h at follow-up (p = n.s.). In a subgroup of 4 subjects with >100 VPBs per hour at follow-up left ventricular mass was increased compared to the others (p < 0.03). Furthermore, regression of sino-atrial (SA) and atrioventricular (AV) blocks was shown. There were no cases of atrial flutter or fibrillation. There was a slight reduction in mean left ventricular wall thickness (9.9 ± 1.2 vs. 9.5 ± 1.4 mm, p < 0.05) and a highly significant reduction of relative wall thickness (0.38 vs. 0.35, p < 0.001). Left ventricular end-diastolic volume (68 ± 6 vs. 70 ± 7 ml ml/m², p = n.s.) and left ventricular mass (109 ± 19 vs. 107 ± 19 g/m², p = n.s.) were unchanged when corrected for body surface area and ejection fraction (EF) increased (60 ± 7 vs. 67 ± 6%, p < 0.01). Parameters of left ventricular diastolic function were normal both at baseline and follow-up. Conclusions: There was no evidence of deleterious cardiac effects of previous top-level endurance athletic activity at 15 years’ follow-up.

Gender-related risk of myocardial involvement in systemic amyloidosis

To investigate associations between gender and myocardial involvement in systemic amyloidosis, we reviewed all patients presenting between 1994 and September 2006 in our institutional network (100 AL and 98 familial transthyretin-related amyloidosis (ATTR) patients, plus 12 elderly men with senile systemic amyloidosis). We focused on echocardiographic descriptors of myocardial involvement (height-indexed mean left ventricular (LV) wall thickness, LV mass index), and baseline LV function. Among familial ATTR patients, female prevalence was lower within the highest tertile of either echocardiographic indicator of myocardial involvement. Gender was independently associated with height-indexed mean LV wall thickness (as were gene mutations). Female prevalence appeared rather similar across the different neurological stages. Within the subgroup of familial ATTR patients with amyloidotic cardiomyopathy, women tended to display a considerably less severe morphological and functional echocardiographic profile. We explored the possible role of female sex hormones by considering menopausal status: women in the highest tertile of mean LV wall thickness index were more often postmenopausal than those in the other two tertiles and had a much higher (∼15 years) mean age; analogous age-related associations were not observable for men. In conclusion, these findings raise the hypothesis that some biological characteristic associated with female gender protects against myocardial involvement in familial ATTR.

Relation of Left Ventricular Chamber Stiffness at Rest to Exercise Capacity in Hypertrophic Cardiomyopathy

The degree of exercise capacity is poorly predicted by conventional markers of disease severity in patients with hypertrophic cardiomyopathy (HC). The principal mechanism of exercise intolerance in patients with HC is the failure of stroke volume augmentation due to left ventricular (LV) diastolic dysfunction. The role of LV chamber stiffness, assessed noninvasively, as a determinant of exercise tolerance is unknown. Sixty-four patients with HC were studied with Doppler echocardiography, exercise testing, and gadolinium cardiac magnetic resonance. The LV chamber stiffness index was determined as the ratio of pulmonary capillary wedge pressure (derived from the E/Ea ratio) to LV end-diastolic volume (assessed by cardiac magnetic resonance). Maximal exercise tolerance was defined as achieved METs. There were inverse correlations between METs achieved and age (r = -0.38, p = 0.003), heart rate deficit (r = -0.39, p = 0.002), LV outflow tract gradient (r = -0.33, p = 0.009), the E/Ea ratio (r = -0.4, p = 0.001), mean LV wall thickness (r = -0.26, p = 0.04), and LV stiffness (r = -0.56, p <0.001) and a positive correlation between METs achieved and LV end-diastolic volume (r = 0.33, p = 0.01). On multivariate analysis, only LV chamber stiffness was associated with exercise capacity. A LV stiffness level of 0.18 mm Hg/ml had 100% sensitivity and 75% specificity (area under the curve 0.84) for predicting < or =7 METs achieved. In conclusion, LV diastolic dysfunction at rest, as manifested by increased LV chamber stiffness, is a major determinant of maximal exercise capacity in patients with HC.

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

Echocardiographic Data in Hungarian Top-Level Water Polo Players

Water polo is a sport involving extremely intense exercise training that might be expected to result in major cardiac adaptations. The purpose of our study was to evaluate cardiac size, determine VO(2max) of top-level water polo players, and compare the findings with those of other top-level athletes. Treadmill VO(2max) and 2D guided M-mode and Doppler echocardiographic data were obtained on players (N = 15) of the Olympic champion (Sydney 2000) Hungarian team and compared with data of Hungarian sedentary subjects (N = 19), and top-level endurance (N = 16) and power athletes (N = 15). Aerobic power of the water polo players was significantly lower (57.8 +/- 12.3 mL.min(-1).kg(-1)) than that of endurance athletes (70.9 +/- 8.9), higher than sedentary controls (49.7 +/- 4.3), and not different from that of power athletes (50.5 +/- 6.0). Body size related mean left ventricular wall thickness (LVWT/BSA(0.5)) was the highest in the water polo players (16.8 +/- 1.5 vs 15.9 +/- 1.1 in endurance, 14.5 +/- 1.0 in the power athletes, and 12.8 +/- 0.6 mm.m in nonathletes). Left ventricular muscle mass (LVMM/BSA(1.5)) was higher in the water polo players (115 +/- 22 g.m) than in power athletes (86 +/- 12) or nonathletes (74 +/- 9) and similar to that of endurance athletes (112 +/- 15). Resting heart rate was lower in the water polo players (55.1 +/- 9.7 beats.m(-1)) and endurance athletes (59.3 +/- 10.6) than in power athletes (66.0 +/- 16.1) or in sedentary subjects (72.9 +/- 10.9). Results indicate that high-level water polo results in marked cardiac hypertrophy that involves predominantly an increase of wall thickness, and in a VO(2max) lower than that of endurance athletes but similar to those of basketball and soccer players.

Reference Values for Valve Circumferences and Ventricular Wall Thicknesses of Fetal and Neonatal Hearts

To evaluate valvular stenosis, cardiac dilation, and/or cardiac hypertrophy, measurements of valve circumference and ventricular wall thickness are of importance. To establish reference values in fetuses and neonates, we reviewed pathology reports at Women and Infants Hospital from 1978 through 2002 and found measurements in 776 cases that were suitable for analysis. Gestational ages (GA) ranged from 15 to 42 wk. The tabulated data include the mean, standard deviation, and 10th and 90th percentile values for foot length, body weight, body length, heart weight, valve measurements, and ventricular wall thicknesses for each week of GA. In cases in which clinical dating is not reliable, we estimated the GA by the mean value nearest that of the observed foot length. All linear measurements increased in a linear fashion throughout the second and third trimesters of development. The circumferences of cardiac valves at all ages, in descending order of magnitude, are: tricuspid, mitral, pulmonary, and aortic. Mean left ventricular (LV) wall thickness is greater than mean right ventricular (RV) wall thickness throughout gestation. The tables offer a means of determining valvular stenosis, or cardiac dilation and/or hypertrophy, based on various gestational ages.

Evaluation of right ventricular dysfunction in patients with cardiac amyloidosis using tei index

Background Cardiac amyloidosis is an infiltrative disease causing predominant diastolic dysfunction and systolic dysfunction at its advanced stage. Right ventricular (RV) dysfunction is an independent predictor of poor prognosis in congestive heart failure and cardiomyopathies. However, the assessment of RV function is still technically difficult because of the complicated geometry of the RV. The recently proposed Tei index, obtained from the cardiac time interval analysis, allows noninvasive and quantitative estimation of global ventricular function without geometric evaluation. Therefore, this study was designed to assess RV function for patients with cardiac amyloidosis. Methods Study patients consisted of 30 consecutive patients with biopsy specimen–proven cardiac amyloidosis and 50 control subjects. Patients were classified as having early or advanced stage of cardiac amyloidosis on the basis of mean left ventricular wall thickness < 15 mm or ≥ 15 mm. Tei index, defined as the sum of isovolumetric contraction and relaxation time divided by ejection time, was obtained from tricuspid and pulmonary Doppler flow velocity. Results RV Tei index was significantly increased for patients with cardiac amyloidosis (0.54 ± 0.16 vs 0.28 ± 0.05, amyloidosis vs control, P < .001). The incidences of abnormal RV isovolumetric contraction time, ejection time, isovolumetric relaxation time, and Tei index in all patients with cardiac amyloidosis were 63%, 43%, 73%, and 83%, respectively. The same incidences were 50%, 13%, 63%, and 75% in the early stage and 68%, 54%, 77%, and 86% in the advanced stage, respectively. Conclusion Patients with cardiac amyloidosis frequently have RV dysfunction even in its early stage. Tei index allows simple, noninvasive, and nongeometric estimation of RV dysfunction in patients with cardiac amyloidosis.

Left ventricular structure and diastolic function with human ageing. Relation to habitual exercise and arterial stiffness.

We sought to determine if attenuation of the age-associated increase in arterial stiffness by habitual aerobic-endurance exercise would have corresponding effects on left ventricular (LV) structure and diastolic function. We performed a cross-sectional study on 138 young, middle-aged, and older men who were either sedentary, recreationally active, or endurance exercise-trained. Ageing was associated with increased large artery stiffness (aortic pulse wave velocity) and habitual aerobic-endurance exercise was associated with decreased large artery stiffness (lower aortic pulse wave velocity; all P<0.05). Ageing was associated with increased mean LV wall thickness, chamber diameter, mass, concentric remodelling, and a decline in LV diastolic function (all P<0.05). Habitual aerobic-endurance exercise was independently associated with increased LV wall thickness, chamber diameter, and mass (echocardiography; P=0.05 or better). The largest LV mass was seen in older endurance trained men, suggesting an additive effect of exercise training and ageing on the LV. Indices of LV diastolic function declined with age, irrespective of habitual physical activity status. Aortic pulse wave velocity was an independent predictor of concentric LV remodelling in the pooled sample, but did not predict other properties of LV structure and diastolic function. In general, habitual aerobic-endurance exercise status was not uniformly associated with favourable modulation of age-associated changes in LV structure and diastolic function. We conclude that in contrast to its ability to favourably modulate the stiffness of large elastic arteries, regular aerobic-endurance exercise does not consistently modulate the changes in LV structure and diastolic function that occur with physiological ageing in men.

Cardiac troponin I in aortic valve disease

Background: Plasma cardiac troponin I levels may be higher than normal in conditions other than ischemic heart disease. We aimed at measuring troponin I levels in aortic valve patients, in which increased values for left ventricular dimensions and pressure are frequently found. Methods: Plasma levels of troponin I, creatine kinase (CK) and the MB fraction of the same enzyme were measured in a group of 25 clinically stable aortic valve patients. Echocardiographic study was performed in all patients; hemodynamic and coronary angiographic study was performed in 19 patients. Troponin I was also measured in a control population ( n=305). Results: The mean value for troponin I was found to be higher in aortic valve patients (0.07±0.02 ng/ml), when compared to controls (0.01±0.02 ng/ml; P<0.05). Significant correlations were found between troponin I and both creatine kinase and its MB fraction. When the 25 patients were divided into two groups, with lower (up to 0.04 ng/ml; 12 patients) and higher (0.05 ng/ml or greater; 13 patients) values for troponin I, patients with higher values were found to have greater mean left ventricular wall thickness (9.9±0.3 mm, n=11, vs. 12.1±0.3 mm, n=13) and pulmonary artery systolic pressures (36.6±2.5 mmHg, n=7, vs. 53.7±3.4 mmHg, n=9). Conclusions: We conclude that slightly raised plasma levels of cardiac troponin I are relatively common in aortic valve patients with no evidence of ischemia. Higher left ventricular wall thickness and pulmonary artery systolic pressure may be related to slightly raised troponin I plasma levels.

Hepatocyte growth factor and left ventricular geometry in end-stage renal disease.

Hepatocyte growth factor is a pleiotropic cytokine with cardioprotective properties. Its serum concentration is markedly raised in end-stage renal disease. This study assessed the relation of hepatocyte growth factor (HGF) with left ventricular mass and geometry in end-stage renal disease. Serum HGF measurements and echocardiographic studies were performed in 185 patients receiving hemodialysis. Patients with serum HGF above the median (1.85 ng/mL) had more frequent cardiovascular complications. This cytokine was directly related to mean left ventricular wall thickness (r=0.23, P=0.002) and relative wall thickness (r=0.25, P=0.0001); a multivariate analysis showed that this relation was independent of other risk factors. Accordingly, the prevalence of left ventricular concentric geometry (either concentric left ventricular hypertrophy or remodeling) was much higher (n=49, 53%) among patients with HGF values above the median that in those with values < or =1.85 ng/mL (n=31, 34%). Furthermore, the risk for left ventricular concentric geometry was higher in patients with HGF values above the median (odds ratio, 2.57; 95% CI, 1.33 to 4.98; P=0.005), and multiple logistic regression analysis confirmed that this association was independent of other risk factors. In patients receiving hemodialysis, elevated serum HGF is associated with concentric left ventricular geometry. This is consistent with reports that link this cytokine to arterial remodeling and survival in patients with end-stage renal disease and suggests that it is part of a counterregulatory response aimed at attenuating cardiovascular damage in this high-risk population.