Higher Left Ventricular Research Articles

Abstract 11125: Increasing Stimulus Strength of Coronary Sinus Pacing Improved Left Ventricular Mechanical Dyssynchrony and Contractile Function in Patients With Reduced Ejection Fraction

Introduction: Increasing stimulus strength of left ventricular (LV) coronary sinus pacing decreases QRS duration and inter-ventricular conduction time. Hypothesis: Increasing stimulus strength of LV coronary sinus pacing improves LV mechanical dyssynchrony and myocardial function. Methods: We studied 36 patients with 6±4 months after cardiac resynchronization therapy (LV ejection fraction: 39±11%). The LV pacing lead was positioned in lateral or posterolateral coronary sinus vein. We measured standard deviation (SD) of time to negative peak circumferential strain (time-CircS) in 6 segments and peak global circumferential strain value (CircS) using two-dimensional speckle-tracking echocardiography to evaluate LV mechanical dyssynchrony and myocardial contractile function, respectively. Low (1.3±0.6V), clinical (2.6±1.0V), and high (7.3±1.1V) voltage conditions of LV coronary sinus pacing were performed under right ventricular pacing-off. Results: SD of time-CircS and global CircS under high voltage LV coronary sinus pacing was significantly better than those under low and clinical voltage (78±38 vs. 90±48 and 92±43msec, p=0.014 and 0.016; 5.7±3.4 vs. 5.4±3.3 and 5.4±3.4%, p=0.007 and 0.003). Moreover, global CircS significantly correlated with SD of time-CircS (r= -0.54, p<0.001, n=108). Conclusions: Increasing stimulus strength of LV coronary sinus pacing improved LV mechanical dyssynchrony and LV contractile function, leading clinical implication for better management of heart failure patients with cardiac resynchronization therapy.

Abstract 19981: Relationship of Cardiorespiratory Fitness and Adiposity With Left Ventricular Peak Systolic Strain in Middle-age Adults: The Dallas Heart Study

Introduction: Low cardiorespiratory fitness (CRF) and obesity are associated with an increased risk for heart failure (HF). However, the mechanisms through which CRF and adiposity might increase HF risk are not fully understood. Because impaired left ventricular (LV) peak systolic strain is an early subclinical marker of HF, we evaluated the association of CRF and adiposity with LV peak systolic strain. Methods: We studied Dallas Heart Study-II participants without cardiovascular disease who had CRF estimated as the peak oxygen uptake from a submaximal treadmill test using the Givoni’s equation and Hellerstein’s formula and total body fat measured by dual x-ray absorptiometry. The participants also had ECG-gated tissue-tagged cardiac MRI imaging using 3-T MRI. Peak mid-wall systolic circumferential strain (Ecc) was determined by harmonic phase imaging. Associations of CRF and measures of overall adiposity [percent body fat (%BF)] and visceral adiposity [waist circumference (WC)] with Ecc were determined using multivariable adjusted linear regression analysis. Results: A total of 1,493 participants (57% women, 42% African Americans) were included in the analysis. After adjustment for baseline risk factors, higher LV mass (β = 0.17; P< .0001), lower ejection fraction (β = -0.32; P = < .0001), higher hs-cTnT levels (β = 0.06; P= 0.04), and lower CRF (β = -0.16; P< .0001) were each associated with higher Ecc (indicating worse systolic function). Higher WC was also significantly associated with higher Ecc (β = 0.07; P= .0006) while %BF was not associated with Ecc (P= 0.08). The relationship between CRF and Ecc did not change after additional adjustment for %BF and other significant confounders (Table). Conclusion: Lower CRF, but not total body fat, is associated with reduced peak systolic strain independent of LV mass and ejection fraction.These findings highlight the independent contributions of low fitness in mid-life towards heart failure risk at a later age.

Abstract 17644: Noninvasive Assessment of Diastolic Myocardial Stiffness by Echocardiography in Patients With Cardiac Amyloidosis

Background: Cardiac amyloidosis (CA) results from extracellular deposition of insoluble amyloid fibrils in the myocardium, leading to myocardial stiffening, restrictive cardiomyopathy and poor prognosis. Thus, measurements of myocardial stiffness might help with identification of patients with cardiac amyloid deposition. The speed of wave transmission of myocardial stretch (Vm) is a novel measure of myocardial elasticity. Our aim was to investigate the behavior of Vm in the left ventricular (LV) myocardium of patients with CA. We hypothesized this wave speed will be increased in these patients and will partly explain the reduction in systolic myocardial function. Methods: We prospectively studied 23 consecutive patients with systemic amyloidosis, of whom 17 (age 59±13 years) had confirmed cardiac involvement (15 AL, 2 TTR), and compared to 18 control subjects (age 47±13 years) with normal LV function. Comprehensive transthoracic echocardiography was performed. Tissue Doppler cineloops (350-450 frames/s) were acquired from 6 LV walls from 3 standard apical views. Regional and global Vm were measured as the wave speed of the onset of myocardial stretch from LV base to apex (late diastole). Results: Subjects with CA (n=17) had higher Vm compared to normal subjects (2.5±0.8 vs 1.5±0.2 m/s; P<0.001, respectively). They also had lower LV ejection fraction (56±11 vs 65±4%; P=0.02), global longitudinal strain (GLS -14±5 vs -20±2%, P<0.001), and myocardial relaxation (mitral annulus septal e’ velocity 4.7±1.9 vs 9.2±2.4 cm/s; P<0.001) and higher LV mass (150±54 vs 87±18 g/m2; P<0.001), left atrial volume (44±7 vs 27±6 mL/m2; P<0.001), and estimated LV filling pressure (E/e’ 20±9 vs 8±3; P<0.001). There was a strong positive association between Vm and LV wall thickness (R=0.62; P<0.001), GLS (R=0.45; P=0.01) and septal E/e’ (R=0.42; P=0.02) and an inverse correlation between Vm and septal e’ (R=-0.39; P=0.03), but not with ejection fraction (P=0.37). Conclusion: This pilot study indicates that Vm is elevated in patients with CA compared to normal subjects, commensurate with the effects of amyloid deposition on LV structure and function. This novel measurement shows promise for noninvasive assessment of diastolic myocardial stiffness in patients with CA.

Abstract 17041: Impact of Different Patterns of Left Ventricular Ballooning in Patients With Stress (Takotsubo) Cardiomyopathy: Single Center Clinical Experience

Introduction: Stress cardiomyopathy (SCMP) is characterized by acute reversible left ventricular (LV) dysfunction, and it is well accepted that SCMP can show various patterns with or without apical involvement. However, clinical data describing characteristics and outcomes according to the patterns of LV ballooning are lacking. Methods: We retrospectively identified 549 consecutive patients (age, 64±15 years; 328 female) with SCMP in a single tertiary hospital from Jan 2009 to June 2014. They were divided into 2 groups with typical apical ballooning (group 1) and atypical patterns sparing the LV apical segment (group 2). Clinical characteristics and outcomes including in-hospital mortality were explored. Results: Apical ballooning was most common (n=394, 71.8%) and group 2 included mid-ventricular ballooning (21.7%), basal ‘inverted’ ballooning (2.9%), global hypokinesia (1.8%), localized ballooning (1.1%), and isolated right ventricular ballooning (0.7%). Group 1 was characterized by higher mean age (67±13 vs. 55±17 years, p<0.001) with higher prevalence of coronary risk factors including obesity, hypertension, hyperlipidemia and diabetes mellitus. Emotional stress was a triggering event in a very limited patients comprising < 5%, whereas physical stress associated with underlying medical conditions comprised more than 70%. Distribution of triggering events was similar between groups. ECG abnormalities including T wave inversion, ST segment elevation, QT prolongation and atrial fibrillation were more frequent in group 1 than group 2 with lower LV ejection fraction. However, in-hospital mortality was comparable between groups (24% vs. 21%, p=0.52). Conclusions: Apical sparing ballooning develops in up to 30% of patients with SCMP. Younger age, favorable medical conditions, less severe ECG changes, and higher LV ejection fraction cannot translate to lower mortality in this group. Physicians’ vigilance is needed to improve clinical outcomes.

Abstract 20350: Discordant Left Bundle Branch Block is Associated With Left Ventricular Dyssyncrhony at Cardiac Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy

LBBB is frequently linked to left ventricular (LV) dyssynchrony and adverse prognosis in HF. LBBB has been defined as concordant (cLBBB) or discordant (dLBBB), when associated in lead I and V5, V6 with a positive or negative T wave respectively. dLBBB has been associated with a worse clinical and prognostic profile in HF patients. We sought to evaluate association between different patterns of LV dV/dT curves at CMR, LBBB morphology, clinical correlates and prognostic role in patients with nonischemic systolic HF. Methods and Results: One hundred and fifteen consecutive patients with LBBB were submitted between 2004 and 2014 to a complete cardiological evaluation, including CMR with analysis of dV/dT curves of LV contraction, and follow-up for cardiac events. We distinguished two different patterns of global and segmental LV systole: a “narrow” pattern (NP) generated by synchronous contraction of wall segments; a “wide” pattern (WP), when delay in contraction between wall segments resulted in a prolungation of systolic peak with a flat or notched morphology. Fourteen patients presenting with normal LV dimensions and function all had cLBBB and NP, while out of 101 patients with HF, those with dLBBB (65%) presented with shorter QRS duration (p < .01) and higher level of NT-proBNP (p < .001). WP was observed more frequent in dLBBB patients (p < .003) as a mark of greater intraventricular dyssynchrony. According to systolic pattern, those with WP had higher levels of NT-proBNP, lower EF and higher LV volumes than those with NP, whereas no significant difference was found in QRS duration. At multivariate analysis only dLBBB (p=.006) and EF (p=.001) were independent predictors of WP. At Kaplan-Meier analysis, the presence of WP was associated with a worse prognosis considering a composite end-point of cardiac death, hospitalization for HF and ICD shock (p<.005). At Cox analysis only presence of WP (p = .029) and level of NT-proBNP (p= .004) were independent predictors. Conclusions: In nonischemic systolic HF patients with LBBB, presence of a WP at CMR dV/dT curves is associated with dLBBB, identifies greater LV dyssynchrony with possible major benefits from resynchronization therapy and is an independent prognosticator.

GENDER DIFFERENCES OF CORONARY HEART DISEASE PATIENTS WITH POSTINFARCTION CARDIOSCLEROSIS AND CHRONIC MITRAL REGURGITATION BY THE DATA OF CORONARY ANGIOGRAPHY REGISTRY

Aim. To reveal gender differences of clinical and functional parameters in postmyocardial infarction patients with chronic mitral regurgitation by data of coronary angiography Registry.Material and methods. Among 15283 patients of Coronary angiography Registry© evaluated from 1991 to 2012 we selected end assessed clinical and functional parameters of 350 men and 53 women with Q-wave myocardial infarction and moderate or severe mitral regurgitation and signs of scars detected by echocardiography.Results. Comparing to the men, women had lower hemoglobin level (135,5±11,3 vs 148,3±14,2 g/l, р<0,001) and rate of smokers (9,8 vs 62,6%, р<0,001). The prevalence of hypothyroidism (29,7 vs 9,6%, р=0,001) and severe MR (17,0 vs 9,1%, р=0,038) were higher in women. They had higher indexes of left atrium size (25,1±2,9 vs 23,7±3,2 mm/m2, р=0,008), left ventricular (LV) posterior wall thickness (6.0±0.7 vs 5,2±0,8 mm/m2, р<0,001), lower extent of LV wall motion abnormalities (28,7±14,7 vs 33,5±14,9%, р=0,036) and higher LV ejection fraction (47,3±8,2 vs 43,9±9,2%, р=0,013). The localization of myocardial scars and coronary stenosis did not differ between men and women. According to the results of multivariate analysis, female gender was independently associated with greater index of LV posterior wall thickness (OR 3,215; CI 1,781–5,804; р<0,001), hypothyroidism (OR 3,070; CI 0,994–9,483; р=0,050), greater body mass index (OR 1,17; CI 1,042–1,317; р=0,008), smoking (ОR 0,056; CI 0,013–0,244; р<0,001) and lower hemoglobin level (OR 0,927; CI 0,890–0,966; р<0,001).Conclusion. There are gender differences in clinical and functional parameters of postmyocardial infarction patients with chronic mitral regurgitation: more severe LV remodeling in women.

Pulse pressure variation is not a valid predictor of fluid responsiveness in patients with elevated left ventricular filling pressure

PurposeThe purpose of this study was to test the hypothesis that the predictive ability of pulse pressure variation (PPV) for fluid responsiveness would be altered in patients with elevated left ventricular (LV) filling pressure. Materials and methodsAccording to the preoperative echocardiographic assessment of the ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E′), patients undergoing surgical coronary revascularization were classified into normal (n = 34, E/E′ <8) and high (n = 34, E/E′ >15) LV filling pressure group. After anesthetic induction, PPV and hemodynamic data were measured before and after 6 mL/kg of colloid administration. Fluid responsiveness was defined as 12% or more increase in stroke volume index assessed by pulmonary artery catheter and tested by the area under the receiver operating characteristic curve (AUROC). ResultsThe AUROCs of PPV in the normal and high filling pressure group were 0.829 (95% confidence interval [CI], 0.661-0.963; P < .001) and 0.583 (95% CI, 0.402-0.749; P = .110), respectively. The AUROCs of cardiac filling pressures and right ventricular end-diastolic volume index did not show statistical significance in both groups. ConclusionsNone of the assessed preload indices including PPV were able to predict fluid responsiveness in patients with elevated LV filling pressure.

Determination of the Longest Intrapatient Left Ventricular Electrical Delay May Predict Acute Hemodynamic Improvement in Patients After Cardiac Resynchronization Therapy

Background— One of the reasons for patient nonresponse to cardiac resynchronization therapy is a suboptimal left ventricular (LV) pacing site. LV electric delay (Q-LV interval) has been indicated as a prognostic parameter of cardiac resynchronization therapy response. This study evaluates the LV delay for the optimization of the LV pacing site. Methods and Results— Thirty-two consecutive patients (23 men; mean age, 71±11 years; LV ejection fraction, 30±6%; 18 with ischemic cardiomyopathy; QRS, 181±25 ms; all mean±SD) underwent cardiac resynchronization therapy device implantation. All available tributary veins of the coronary sinus were tested, and the Q-LV interval was measured at each pacing site. The hemodynamic effects of pacing at different sites were evaluated by invasive measurement of LV d P /d t max at baseline and during pacing. Overall, 2.9±0.8 different veins and 6.4±2.3 pacing sites were tested. In 31 of 32 (96.8%) patients, the highest LV d P /d t max coincided with the maximum Q-LV interval. Q-LV interval correlated with the increase in LV d P /d t max in all patients at each site (AR1 ρ=0.98; P &lt;0.001). A Q-LV value &gt;95 ms corresponded to a &gt;10% in LV d P /d t max . An inverse correlation between paced QRS duration and improvement in LV d P /d t max was seen in 24 patients (75%). Conclusions— Pacing the LV at the latest activated site is highly predictive of the maximum increase in contractility, expressed as LV d P /d t max . A positive correlation between Q-LV interval and hemodynamic improvement was found in all patients at every pacing site, a value of 95 ms corresponding to an increase in LV d P /d t max of ≥10%.

Microvascular obstruction assessed by 3-tesla magnetic resonance imaging in acute myocardial infarction is correlated with plasma troponin I levels.

BackgroundMicrovascular obstruction (MVO) at the acute phase of myocardial infarction (MI) is associated with poor prognosis. We aimed to evaluate the correlation between plasma cardiac troponin I (cTnI) at the acute phase of MI and extent of no-reflow, as assessed by 3-T cardiac magnetic resonance imaging (MRI). Secondly, we defined a cut-off value for cTnI predictive of no-reflow.Methods51 consecutive patients with no previous history of cardiovascular disease, presenting ST elevation MI within <12 h. Infarct size and extent of no-reflow were evaluated by 3-T MRI at day 5. Extent of no-reflow at 15 minutes (MVO) was correlated with cTnI at admission, 6, 12, 24, 48 and 72 hours. At 6 months, MRI was performed to evaluate the impact of MVO on LV remodeling.ResultsMVO was diagnosed in 29 patients (57%). Extent of MVO was significantly correlated to peak troponin, cTnI (except admission values) and area under the curve. Using Receiver-operating characteristic (ROC) curve analysis, a cut-off cTnI value >89 ng/mL at 12 h seemed to best predict presence of early MVO (sensitivity 63%, specificity 88%). At 6 months, MVO was associated with left ventricular (LV) remodeling, resulting in higher LV volumes.ConclusionThere is a relationship between cTnI at the acute phase of AMI and extent of MVO as assessed by 3-T cardiac MRI. A cut-off cTnI value of 89 ng/mL at 12 h seems to best predict presence of MVO, which contributes to LV remodeling.

Nongenomic effects of estrogen mediate the dose‐related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats (652.19)

Acute ethanol lowers blood pressure (BP) and cardiac output in proestrus and after chronic estrogen (E2) replacement in ovariectomized (OVX) female rats. However, whether rapid nongenomic effects of E2 mediate these hemodynamic effects of ethanol remained unanswered. To test this hypothesis, we investigated the effect of ethanol (0.5, 1 or 1.5 g/kg; i.v.) on left ventricular (LV) function and oxidative markers in OVX rats pretreated 30 min earlier with 1 μg/kg E2 (OVXE2) or vehicle (OVX) and in proestrus sham‐operated (SO) rats. In SO rats, ethanol caused significant and dose‐ related reductions in BP, rate of rise in LV pressure (LV dP/dtmax), and LV developed pressure (LVDP). The ethanol effects disappeared in OVX rats and were restored in OVXE2 rats suggesting rapid estrogen receptor signaling mediates the detrimental LV effects of ethanol. The E2‐dependent LV dysfunction caused by ethanol was associated with higher LV: (i) generation of reactive oxygen species, (ii) expression of the malondialdehyde and 4‐hydroxynonenal protein adducts, (iii) Akt and ERK1/2, and (iv) catalase activity. Collectively, it is concluded that rapid estrogen receptor signaling is implicated in the cellular events that lead to the generation of aldehyde protein adducts and Akt/ERK1/2 phosphorylation, which ultimately mediate the estrogen‐dependent LV oxidative stress and dysfunction caused by ethanol in female rats. Grant Funding Source: Supported by NIAAA [2R01 AA014441‐07]

Abstract P015: Fibroblast Growth Factor 23 and Echocardiographic Measures of Cardiac Structure and Function among African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Fibroblast growth factor 23 (FGF23), an endocrine hormone, induced left ventricular (LV) hypertrophy through direct action in experimental animal models. The association of FGF23 with echocardiographic measures in humans is relatively uncharacterized. Hypothesis: Higher levels of FGF23 will be cross-sectionally associated with more adverse echocardiographic measures of LV structure and function. Methods: We conducted a cross-sectional analysis of 2086 African-American adults (66% female, median age 55) from a subset of the ARIC Study, a community-based cohort in the United States. Intact active FGF23 was assessed in blood samples collected at ARIC visit two (1990-1992). Echocardiography was performed at visit three (1993-1995) in participants recruited at the Jackson field center only. We used multivariable linear regression to evaluate the associations of FGF23 (per 15 pg/mL change) with echocardiographic measures after adjustment for traditional cardiovascular risk factors assessed at visit two. We also examined differences in observed associations by age and sex using interaction terms. Results: FGF23 was significantly associated with greater left atrial diameter and LV mass index (Table). A significant sex interaction was identified for LV diameter (p-interaction = 0.005). No association was observed in men while a positive association was observed among women. An adverse, decreasing trend in percent fractional shortening of the LV diameter at higher levels of FGF was stronger in individuals aged &gt;55 (p-interaction = 0.03). No linear association was found between FGF23 and E/A ratio. Conclusion: FGF23 was associated with higher LV mass, larger LV size, and lower LV systolic function. These findings are consistent with results from experimental animal studies and provide evidence suggesting that cardiac structure and function may be influenced by FGF23 in humans. Prospective studies are needed to evaluate whether FGF23 is associated with change in markers of cardiac structure and function.

CMR survey in Thalassemia Intermedia patients

Results One-hundred and eighty-eight (74.6%) patients showed no MIO in any segment, 56 (22%) had an heterogeneous distribution (52 with global heart T2*≥20 ms), and 8 (0.3%) showed an homogeneous MIO. Left ventricular (LV) and right ventricular (RV) dilatations were present in 113 (45%) and in 49 (19%) patients, respectively. LV dysfunction was present in the 18.0% of the cases while RV dysfunction in the 3.63%. High LV mass indexes were present in 22 (8.7%) patients. Fifty-two/227 (22.9%) patients showed myocardial fibrosis. Myocardial fibrosis was associated to LV dysfunction (P = 0.001) and high mass indexes (P = 0.038). One-hundred and fourteen patients were non-transfusion dependent (transfusion requirements absent or sporadic) while 138 patients were transfusion-dependent (regular transfusions). The mean age at start of chronic transfusions was 11.8 ± 12.3 years. Table 1 shows the comparison between the two groups. Non-transfusion-dependent patients showed significantly higher global heart T2* values and MIO with a global heart T2* < 20 ms was detected in two of them (one requiring occasional blood transfusions and one non transfused). Biventricular end-diastolic volume index, stroke volume index, left ventricular (LV) mass index, and LV cardiac index were significantly higher in the non-transfusion dependent group.

Nongenomic effects of estrogen mediate the dose-related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats

Acute ethanol lowers blood pressure (BP) and cardiac output in proestrus and after chronic estrogen (E2) replacement in ovariectomized (OVX) female rats. However, whether rapid nongenomic effects of estrogen mediate these hemodynamic effects of ethanol remains unanswered. To test this hypothesis, we investigated the effect of ethanol (0.5 or 1.5 g/kg iv) on left ventricular (LV) function and oxidative markers in OVX rats pretreated 30 min earlier with 1 μg/kg E2 (OVXE2) or vehicle (OVX) and in proestrus sham-operated (SO) rats. In SO rats, ethanol caused significant and dose-related reductions in BP, rate of rise in LV pressure (LV dP/dtmax), and LV developed pressure (LVDP). These effects of ethanol disappeared in OVX rats and were restored in OVXE2 rats, suggesting rapid estrogen receptor signaling mediates the detrimental effects of ethanol on LV function. Ex vivo studies revealed that the estrogen-dependent myocardial dysfunction caused by ethanol was coupled with higher LV 1) generation of reactive oxygen species (ROS), 2) expression of malondialdehyde and 4-hydroxynonenal protein adducts, 3) phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2), and 4) catalase activity. ERK1/2 inhibition by PD-98059 (1 mg/kg iv) abrogated the myocardial dysfunction, hypotension, and the elevation in myocardial ROS generation caused by ethanol. We conclude that rapid estrogen receptor signaling is implicated in cellular events that lead to the generation of aldehyde protein adducts and Akt/ERK1/2 phosphorylation, which ultimately mediate the estrogen-dependent LV oxidative stress and dysfunction caused by ethanol in female rats.

Left Ventricular Systolic and Diastolic Function in Normotensive Type 2 Diabetic Patients With or Without Autonomic Neuropathy

We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n=24), patients with DAN (n=35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1%±8.2% vs 26.5%±5.1%; P=.031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8±6.3 vs 69.3±3.3 bpm; P<.0001) and a higher rest LV workload (10,072±1165 vs 8606±1075 bpm mm Hg; P<.0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.

CMR Survey In a Large Cohort Of TI Patients

IntroductionLittle is known about cardiac involvement in thalassemia intermedia (TI) using cardiovascular magnetic resonance (CMR). We investigated myocardial iron overload (MIO), biventricular parameters, and myocardial fibrosis in a large cohort of TI patients, underlying the differences between transfusion-dependent and non-transfusion-dependent patients. MethodsWe studied 252 adult TI patients (119 females, 39.5±10.4 years) enrolled in the MIOT Network. MIO was assessed using a multislice multiecho T2* approach. Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement acquisitions. ResultsOne-hundred and eighty-eight (74.6%) patients showed no MIO in any segment, 56 (22%) had an heterogeneous distribution (52 with global heart T2*≥20 ms), and 8 (0.3%) showed an homogeneous MIO.Left ventricular (LV) and right ventricular (RV) dilatations were present in 113 (45%) and in 49 (19%) patients, respectively. LV dysfunction was present in the 18.0% of the cases while RV dysfunction in the 3.63%. High LV mass indexes were present in 22 (8.7%) patients.Fifty-two/227 (22.9%) patients showed myocardial fibrosis. Myocardial fibrosis was associated to LV dysfunction (P=0.001) and high mass indexes (P=0.038).One-hundred and fourteen patients were non-transfusion dependent (transfusion requirements absent or sporadic) while 138 patients were transfusion-dependent (regular transfusions). The mean age at start of chronic transfusions was 11.8 ± 12.3 years. Table 1 shows the comparison between the two groups. Non-transfusion-dependent patients showed significantly higher global heart T2* values and MIO with a global heart T2* < 20 ms was detected in two of them (one requiring occasional blood transfusions and one non transfused). Biventricular end-diastolic volume index, stroke volume index, left ventricular (LV) mass index, and LV cardiac index were significantly higher in the non-transfusion dependent group.Table 1Non-transfusion-dependentTransfusion-dependentPAge39.9 ± 11.539.2 ± 9.40.922Sex (M/F)67/4766/720.083Global heart T2* (ms)38.8 ± 6.735.5 ± 9.20.014MIO pattern, N (%):No MIOHeterogeneous MIO with global T2* ≥ 20 msHeterogeneous MIO with global T2* < 20 msHomogeneous MIO92 (80.7)20 (17.5)1 (0.9)1 (0.9)96 (69.6)32 (23.2)3 (2.2)7 (5.1)0.103LV end-diastolic volume index (ml/m2)99.4 ± 19.692.9 ± 19.10.009LV end-systolic volume index (ml/m2)36.6 ± 11.434.9 ± 10.40.249LV stroke volume index62.9 ± 12.458.6 ± 13.10.007LV mass index (g/m2)69.9 ± 13.963.9 ± 12.90.004LV ejection fraction (%)63.7 ± 6.862.5 ± 6.60.163LV cardiac index (L/min/m2)7.6 ± 2.36.5 ± 2.20.002LGE, N (%)20/105 (19)32/122 (26.2)0.199RV end-diastolic volume index (ml/m2)92.0 ± 23.386.5 ± 20.80.048RV end-systolic volume index (ml/m2)32.7 ± 14.931.8 ± 11.30.571RV stroke volume index58.5 ± 14.954.5 ± 14.30.017RV ejection fraction (%)64.7 ± 8.363.3 ± 7.50.168 ConclusionsCMR plays a key role in the management of TI patients. Heart iron (global heart T2* < 20 ms) was not common, but a quarter of the patients had some pathological segments. A consistent number of patients had the stigmata of the high cardiac output state cardiomyopathy. Myocardial fibrosis was related to the high cardiac output state. The signs of the high output state were controlled in the transfusion-dependent-patients. Disclosures:No relevant conflicts of interest to declare.

Pericardial fat, insulin resistance, and left ventricular structure and function in morbid obesity

Background and aimMorbid obesity is often accompanied by insulin resistance and increased ectopic fat surrounding the heart. We evaluated the relation of epicardial and pericardial fat with insulin resistance and left ventricular (LV) structure and function. Methods and resultsEpicardial and pericardial fat thicknesses were determined at 2-dimensional echocardiography in 80 morbid obese subjects [age 42 ± 12 years, 31% men, body mass index (BMI) 44.4 ± 7 kg/m2]. LV hypertrophy (LV mass ≥51 g/m2.7), inappropriately high LV mass for a given cardiac workload (observed vs predicted LV mass >128%), and stress-adjusted LV mid-wall fractional shortening were determined. Pericardial and epicardial fat thicknesses had direct associations with BMI (r = 0.40 and 0.45, both p < 0.01) and waist circumference (r = 0.37 and 0.45, both p < 0.01). Pericardial (partial r = 0.35, p < 0.01), but not epicardial fat thickness (partial r = 0.05, p = n.s.), was correlated with homeostasis model assessment-insulin resistance after adjustment for BMI. Pericardial fat also had a strong negative correlation with mid-wall fractional shortening (p = 0.01) and a positive one with inappropriately high LV mass (p < 0.01), while no such relation was found for epicardial fat (both p = n.s.). Independently of age, male sex, BMI, and anti-hypertensive treatment, pericardial fat thickness had an independent positive association with inappropriately high LV mass (β = 0.29, p = 0.02), and a negative one with stress-adjusted mid-wall fractional shortening (β = −0.26, p = 0.04). ConclusionsPericardial fat thickness is associated with insulin resistance, inappropriately high LV mass, and LV systolic dysfunction in obese individuals. Findings from this study confirm the existence of a connection between insulin resistance, cardiac ectopic fat deposition and cardiac dysfunction in morbid obesity.

Impaired Left Ventricular Filling in COPD and Emphysema: Is It the Heart or the Lungs?: The Multi-Ethnic Study of Atherosclerosis COPD Study

COPD and heart failure with preserved ejection fraction overlap clinically, and impaired left ventricular (LV) filling is commonly reported in COPD. The mechanism underlying these observations is uncertain, but may include upstream pulmonary dysfunction causing low LV preload or intrinsic LV dysfunction causing high LV preload. The objective of this study is to determine if COPD and emphysema are associated with reduced pulmonary vein dimensions suggestive of low LV preload.The population-based Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50 to 79 years who were free of clinical cardiovascular disease. COPD was defined by spirometry. Percent emphysema was defined as regions &lt; -910 Hounsfield units on full-lung CT scan. Ostial pulmonary vein cross-sectional area was measured by contrast-enhanced cardiac magnetic resonance and expressed as the sum of all pulmonary vein areas. Linear regression was used to adjust for age, sex, race/ethnicity, body size, and smoking.Among 165 participants, the mean (± SD) total pulmonary vein area was 558 ± 159 mm2 in patients with COPD and 623 ± 145 mm2 in control subjects. Total pulmonary vein area was smaller in patients with COPD (-57 mm2; 95% CI, -106 to -7 mm2; P = .03) and inversely associated with percent emphysema (P &lt; .001) in fully adjusted models. Significant decrements in total pulmonary vein area were observed among participants with COPD alone, COPD with emphysema on CT scan, and emphysema without spirometrically defined COPD.Pulmonary vein dimensions were reduced in COPD and emphysema. These findings support a mechanism of upstream pulmonary causes of underfilling of the LV in COPD and in patients with emphysema on CT scan.

Impact of left ventricular systolic diameter on the in-hospital improvement of systolic function in acute decompensated heart failure with high blood pressure presentation

Purpose: In-hospital improvement of left ventricular (LV) systolic function is frequently observed in acute decompensated heart failure (ADHF) patients presented with high systolic blood pressure (SBP) on admission. However, determinants of improved LV systolic function in patients with ADHF remain unclear. Methods: We examined 214 consecutive patients admitted by ADHF with SBP > 140 mmHg, impaired LV systolic function, defined as LV ejection fraction (EF) < 50% or fractional shortning < 26%, but no acute coronary syndrome. Patients were divided into 2 groups according to the presence or absence of improved LV systolic function, defined as normalized predischarge LV systolic function. Results: Improved LV systolic function was observed in 54 patients and length of hospital stay was comparable between two groups. Patients with improved LV systolic function had lower BNP level, smaller LV systolic and diastolic diameters at admission, higher baseline and % increase of LV systolic function than those without. ROC curves showed that smaller LV systolic diameter (LVSD) at admission was superior to other variables for predicting improved LV systolic function (AUC: 0.80) (Figure). Multivariate logistic regression analysis showed that smaller LVSD (<46mm) was the strongest independent determinant for improvement of LV systolic function (OR: 6.51, 95% CI: 1.60-26.34, p=0.0086) among variables including lower BNP level (OR: 2.09, 95% CI: 1.01-4.30), no history of coronary artery disease (OR: 2.37, 95% CI: 1.12-5.01), and LV diastolic diameter at admission (p = 0.98). ![Figure][1] Figure 1 Conclusions: Smaller LVSD at admission was the strongest determinant for in-hospital improvement of LV systolic function in patients with ADHF with high blood pressure and impaired LV systolic function. [1]: pending:yes

Latent Transforming growth factor Binding Protein 2 (LTBP2) is related to phenotypic changes suggestive for HFPEF in stable outpatients with coronary artery disease and preserved ejection fraction

Purpose: The Latent Transforming growth factor Binding Protein 2 (LTBP2) was recently discovered in an unbiased proteomics search for novel markers in patients with acute dyspnea. The highest levels of LTBP2 are found in lung tissue and plasma levels of LTBP2 are a powerful predictor of all-cause mortality in patients presenting with acute dyspnea. We evaluated the relationship between plasma levels of LTBP2 and phenotypic changes suggestive for heart failure with preserved ejection fraction (HFPEF) including parameters of neurohormonal activation, Left Ventricular (LV) remodeling and filling pressures as well as exercise capacity. Methods: We studied 136 stable patients with CAD and LVEF≥50% (mean age 68±8 years, 76% men, LVEF 63±8%, 37% in NYHA class II/III). All patients underwent resting echocardiography for evaluation of LVEF and volumes, TDI derived longitudinal systolic and diastolic velocities function and E/E', as well as a six minute walking distance test (6minWD), maximal bicycle spiroergometry (peakVO2 and VE/VCO2 slope, n=104) and blood sampling. A proteomic approach for antibody-free targeted protein quantification based on high-end mass spectrometry was used to measure LTBP2 levels. Results: Levels of LTBP2 were higher in NYHA II/III as compared to NYHA I patients (p<0.05) and were correlated with NT-proBNP levels (r=0.49, p<0.01). ROC analysis showed a comparable modest AUC of 0.61 (p<0.05) for NT-proBNP and 0.60 (p<0.05) for LTBP2 to discern NYHA I versus NYHA II/III patients. LTBP2 levels were correlated with LV volumes (r=-0.38, p<0.01 for LVEDV, r=-0.33, p<0.01 for LVESV) as well as with LV longitudinal systolic velocities (r=-0.35, p<0.01), LV early diastolic velocities (r=-0.31,p<0.01) and E/E' (r=0.28,p<0.01). In linear regression analysis, including age and creatinine, LVESV and E/E' were independent predictors for LTBP2 levels (all p<0.05). Higher levels of LTBP2 were associated with lower 6minWD (r=-0.43, p<0.001), lower peakVO2 (r=-0.38, p<0.001) and higher VE/VCO2 slope (r=0.36, p<0.001). In multiple linear regression analysis including age, creatinine, LVESV and E/E', LTBP2 levels appeared to be an independent predictor for both 6minWD and peakVO2 (p<0.01). Conclusion: In stable patients with CAD and preserved LV function, higher levels of LTBP2 are related to phenotypic changes suggestive for HFPEF including higher neurohormonal activation, adverse LV remodeling with loss of longitudinal function, higher LV filling pressures and a lower exercise capacity. Therefore, the role of LTBP2 in the development, diagnosis and outcome of HFPEF deserves further study.

Higher fibroblast growth factor-23 concentrations associate with left ventricular systolic dysfunction in dialysis patients

Aims: The concentration of fibroblast growth factor 23 (FGF-23) is elevated in patients on dialysis. FGF receptors have been implicated in the pathogenesis of left ventricular (LV) hypertrophy. The objective of this study was to examine the associations between high plasma FGF-23 concentration and LV systolic dysfunction. Methods: We tested the hypothesis that high plasma FGF-23 concentration is associated with LV dysfunction in 110 chronic dialysis patients from the Homocysteine study who had paired echocardiograms performed for clinical indications. C-terminal FGF-23 concentrations were measured in stored plasma samples. Multivariate regression analyses were performed to evaluate the association of FGF-23 concentration with LV dysfunction. Results: Participants had a mean age of 60 ± 11 years. Median FGF-23 level and mean ejection fraction (EF) at baseline were 4,632 (1,384 – 14,997) RU/ml and 50 ± 13%, respectively. Median follow-up time was 1.9 years. Higher FGF-23 concentration was directly associated with decreases in EF during follow-up. After adjustment for demographics, baseline EF, hypertension, diabetes, cardiovascular disease, body mass index, systolic blood pressure, hemoglobin and markers of mineral metabolism, participants with FGF-23 in the highest tertile had an 8% decrease in EF compared to participants in the lowest tertile (β –8.0, 95% CI –15.5 to –0.53; p = 0.04). When FGF-23 was evaluated as a continuous variable, for every log10 increase in FGF-23, EF decreased during follow-up by 6.5% (β –6.5, 95% CI –11.3 to –1.73; p = 0.01). Conclusion: In conclusion, higher FGF-23 concentration is independently associated with LV systolic dysfunction in chronic dialysis patients.