Adverse effect of increased left ventricular wall thickness on five year outcomes of patients with negative dobutamine stress

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Title:
Adverse effect of increased left ventricular wall thickness on five year outcomes of patients with negative dobutamine stress
Series Title:
Journal of Cardiovascular Magnetic Resonance
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Book
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English
Creator:
Walsh, Thomas F.
Dall'Armellina, Erica
Chughtai, Haroon
Morgan, Timothy M.
Ntim, William
Link, Kerry M.
Hamilton, Craig A.
Kitzman, Dalane W.
Hundley, W. Gregory
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BioMed Central
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Abstract:
Background: To determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis. Results: Between 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducible WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization. In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT ≥12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization (HR 3.0, p = 0.0005). Conclusion: Similar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.

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University of Florida
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doi - 10.1186/1532-429X-11-25
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Abstract
Background
To determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis.
Results
Between 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducible WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization.
In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT ≥12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization (HR 3.0, p = 0.0005).
Conclusion
Similar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.
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Walsh, Thomas F
Dall'Armellina, Erica
Chughtai, Haroon
Morgan, Timothy M
Ntim, William
Link, Kerry M
Hamilton, Craig A
Kitzman, Dalane W
Hundley, W Gregory
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Journal of Cardiovascular Magnetic Resonance. 2009 Aug 03;11(1):25
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Bio Med Central Page 1 of 9(page number not for citation purposes) Journal of Cardiovascular Magnetic Resonance Open Access ResearchAdverse effect of increased left ve ntricular wall thickness on five year outcomes of patients wi th negative dobutamine stressThomasFWalsh†1, EricaDall'Armellina†1, HaroonChughtai1, TimothyMMorgan†2, WilliamNtim†1, KerryMLink†1, CraigAHamilton†3, DalaneWKitzman†1 and W GregoryHundley*1,4Address: 1Department of Internal Medicine (Cardiology Section), Wake Forest University School of Medicine Medical Center Boulevard, Wins tonSalem, North Carolina, USA, 2Division of Public Health Sciences, Wake Forest Universi ty School of Medicine, Medica l Center Boulevard, WinstonSalem, North Carolina, USA, 3Department of Biomedical Engineering, Wake Forest University School of Medicine, Medical Ce nter Boulevard, Winston-Salem, North Carolina, USA and 4Department of Radiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA Email: ThomasFWalsh-Thomas.Walsh@jax.ufl.edu; EricaDall'Armellina-edallarme@gmail.com; HaroonChughtai-eras_27@yahoo.com; TimothyMMorgan-tomorgan@wfubmc.edu; WilliamNtimwntim@wfubmc.edu; KerryMLink-klink@wfubmc.edu; CraigAHamilton-crhamilt@wfubmc.edu; DalaneWKitzman-dkitzman@wfubmc.edu; W GregoryHundley*-ghundley@wfubmc.edu Corresponding author †Equal contributors AbstractBackground: To determine if patients without dobutam ine induced left ventricular wall motion abnormalities (WMA) but an increa sed LV end-diastolic wall thickn ess (EDWT) exhibit a favorable cardiac prognosis. Results: Between 1999 and 2001, 175 patients underwe nt a dobutamine stress cardiovascular magnetic resonance (DCMR) proced ure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducibl e WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medica l records were reviewed to determine the post-DCMR occurr ence of cardiac death, myocardi al infarction (MI), and unstable angina (USA) or congestive heart fa ilure (CHF) warranting hospitalization. In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine grad ient-echo derived LV EDWT 12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting ho spitalization (HR 3.0, p = 0.0005). Conclusion: Similar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prog nostic studies of the importance of LV wall thickness and mass meas ured with steady-state free pr ecession techniques are warranted.Published: 3 August 2009 Journal of Cardiovascul ar Magnetic Resonance 2009, 11 :25doi:10.1186/1532-429X-11-25 Received: 3 July 2008 Accepted: 3 August 2009 This article is available from: http ://www.jcmr-online.com/content/11/1/25 2009 Walsh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 2 of 9(page number not for citation purposes)BackgroundLeft ventricular (LV) wall motion abnormalities (WMA) induced during intravenous dobutamine are associated with flow limiting epicardial coronary artery stenoses, and predict future cardiac events including myocardial infarction (MI) and cardiac death [1-4]. Typically, if resting LV end-diastolic wall thickness (EDWT) is normal, the absence of dobutamine inducible WMA identifies a group of individuals with a low risk of experiencing future cardiac events [5,6]. Importantly however, in individuals with increased resting LV EDWT, the sensitivity of dobutamine induced LV WMA for identifying flow limiting epicardial stenoses is low (36%) [7]. Also, data from Framingham have shown that increased LV EDWT itself is an independent predictor of cardiac events [8]. To date, it remains uncertain whether individuals with increased resting LV EDWT and an absence of inducible LV WMA during intravenous dobutamine remain at a relatively low risk of developing a future cardiac event. This study was performed to determine if the absence of inducible WMA during intravenous dobutamine would be associated with a favorable cardiac prognosis regardless of resting LV EDWT. To address this question, we measured LV EDWT and performed extensive follow-up on individuals undergoing dobutamine stress cardiovascular magnetic resonance (DCMR) examinations with cine white blood fast-gradient echo techniques.MethodsPopulation and Study DesignThe study complies with the Declaration of Helsinki, and was approved by the Institutional Review Board at the Wake Forest University School of Medicine. All patients gave both verbal (for performing follow-up questionnaire) and written (for CMR and later for review of medical records) informed consent. Between 1997 and 2001, 175 consecutive participants with a LV ejection fraction >55%, and no inducible LV WMA indicative of ischemia in any of 17 myocardial segments during DCMR were enrolled in the study. After DCMR, participants blinded to DCMR test results performed the outcomes analysis.Dobutamine/Atropine Card iovascular Magnetic ResonanceAs previously described [3,5], images were obtained on a Horizon 1.5T whole-body imaging system (General Electric Medical Systems) using cine white blood spoiled gradient-echo imaging with a 256 128 matrix, a 3548-cm field of view, a 4-ms echo time, a 10-ms repetition time, a 20-degree flip angle, an 8-mm slice thickness, a 40-ms temporal resolution, and 8 to 12 second periods of breath holding. Each of the patients received atropine if they were unable to obtain 80% maximum predicted heart rate for age (n = 95). Findings of this heart rate response have been shown at our institution to be 83% sensitive and 83% specific for identifying >50% coronary arterial luminal narrowings during dobutamine/atropine stress, and have been shown to forecast future cardiac events [3,5]. At rest and during graded doses of dobutamine/atropine stress, LV wall motion was confirmed as normal across all 17 myocardial segments [5]. The resting LV ejection fraction was measured using a biplane area-length technique [9]. According to previously published techniques, the posterior and septal wall thicknesses were measured at the level of the LV minor dimension, at the mitral chordae level using the end-diastolic, left ventricular 3-chamber (equivalent to transthoracic echocardiography parasternal long-axis) view (Figure 1) [10]. At the time of testing, the occurrence of a prior Q-wave myocardial infarction [11], and the presence of cardiac risk factors [including a history of diabetes [12], smoking, coronary revascularization, elevated total cholesterol [13], and hypertension [14] were recorded.OutcomesWithin 7 years of the DCMR exam, each participant was contacted to determine the post-procedure occurrence of cardiac events. All persons were contacted initially by phone or personal interview. If deceased, the next of kin was contacted. Questions were administered to identify the possibility of myocardial infarction (MI), unstable angina (USA) or congestive heart failure (CHF). Any In accordance with the Americ an Society of Echocardiography, posterior (green line) and se ptal (red line) left ventricular wall thickness was measured in the left ventricular long axis view at end diastole at approximately the level of the mitral valve leaflet tips (LV = le ft ventricle; LA = left atrium; and Ao = aorta) Figure 1 In accordance with the Am erican Society of Echocardiography, posterior (green line) and septal (red line) left ventricular wall thickn ess was measured in the left ventricular long axis view at end diastole at approximately the level of the mitral valve leaflet tips (LV = left ventricle; LA = left atrium; and Ao = aorta) LV LAAo

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 3 of 9(page number not for citation purposes)change in physical state, medical condition, or medicationwas confirmed in all cases by review of the participant's medical records. If an event was suspected or identified during contact with the participant, medical records from the site of the event were obtained and confirmation of the event was determined according to data collected from the medical record. Established, published criteria were utilized to define events. Hard events were defined as cardiac death (death in the presenceof acute MI, significant cardiac arrhythmia, or refractory CHF [15], or MI (angina of >30 minutes durationand either 2 mm ST segment elevation in 2 consecutive ECG leadsor a rise in cardiac enzymes including creatine kinase level MB fraction cardiac troponin-I above normal limits) [16]. Electrocardiographic, enzymatic, or autopsy data were used tosubstantiate cardiac mortality. Any events were defined as hard events and/or USA, or CHF warranting hospital admission. In the case of 2 simultaneouscardiac events, the worst event was chosen (cardiac death>MI> USA>CHF).Statistical AnalysisAfter all records were obtained, a statistical analysis was conducted using SAS 9.1 (SAS Institute, Cary, NC) for Windows. Based on previously published criteria, participants were dichotomized into those with a LV EDWT < or 12 mm [15]. In this study, we determined LV EDWT in the septum, posterior wall, and the average of the two. The average LV EDWT of the septal and posterior walls served as the primary outcome measure. All grouped data were expressed as mean SD. Independent predictors of events were identified using univariate and multivariate Cox proportional hazards regression models. The risk of a given variable was expressed by a hazard ratio (HR) with corresponding 95% CIs. A variable was considered significant if the null hypothesis of no contribution could be rejected at a probability value of <0.05. The probability of the presence or absence of hard events as a function of follow-up duration was estimated by the Kaplan-Meier method and compared between groups by use of the log-rank test. Unadjusted, Framingham adjusted, and additional cardiac MI risk factor adjusted Cox proportional hazard regression models were used to predict cardiac events. To determine the intra observer variability for measuring LV EDWT, a randomly selected sample of 20 participants was analyzed twice separated by 1 year. To determine inter observer agreement in measures of LV EDWT, this same sample from 20 participants was analyzed by a separate individual. In both the intra and inter observer comparisons, repeat assessments were performed in an unpaired fashion blinded to the results of prior analyses. The authors had full access to the data and take responsibility for its integrity.ResultsContact was made with all 175 patients; their clinical data are displayed in Table 1. Those with an average (septal and posterior wall) LV EDWT 12 mm were older, and exhibited more prior CAD, hypertension, diabetes, and lung disease. Overall, the amount of dobutamine administered was 30 10 g/kg/min and did not differ between those with and without a LV EDWT < or 12 mm. Rest and stress hemodynamic assessments at the time of DCMR stress were similar for those with or without LV EDWT < or 12 mm (Table 2). Over the 5.5 average years of follow-up, the rate of hard events was 8.4% (Table 3). The 5.5 year hard event rate was 3.2% for the patients with a LV EDWT <12 mm compared to 20.3% for those with a LV EDWT 12 mm. The EDWT for the posterior wall averaged 12 3 mm in participants with no events, and 14 3 mm in participants with any events (p < 0.001). Similarly, the septal wall thickness in patients without events was 12 3 mm compared to 14 4 mm for those with any events (p < 0.001). The septal and posterior wall thickness among the participants were highly correlated (r = 0.76, p = 0.001). There was no difference in the predictive accuracy of the septal, posterior, or combined average of the wall thickness for identifying those at risk of future cardiac events. The proportion of participants free of both hard and any cardiac events is shown in Figure 2. A LV EDWT 12 mm was predictive of both any and hard events in a) the unadjusted model, b) the Framingham risk factor adjusted model, and c) after adjustment for factors associated with CAD, MI, and cardiac events (Figure 3 and Table 4). We also performed analyses treating LV EDWT as a continuous, as opposed to dichotomous (< or 12 mm thick) variable. Using the proportional hazard wall thickness as a continuous variable demonstrated a significant trend of increasing risk of hard events (p = 0.004) and any events (p = 0.001) with increasing LV EDWT. The intra observer correlation of LV EDWT was 0.73, and the inter observer assessment of LV EDWT was 0.77.DiscussionPrior studies have found that increased LV EDWT during a dobutamine stress test is associated with a decreased sensitivity for detecting flow limiting coronary arterial luminal narrowings detected with contrast coronary angiography [7]. Other studies have identified an association between the presence of LV hypertrophy or increased LV EDWT and an adverse cardiac prognosis [8,17-19]. In many countries, dobutamine stress echocardiography is performed widely for individuals suspected to have or possessing coronary arteriosclerosis, MI, or CHF. Individuals without inducible LV WMA are ascribed a favorable

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 4 of 9(page number not for citation purposes)Table 1: Demographic dataLV EDWTLV EDWT p -value Total 12 mm>12 mm n = 175n = 98n = 77 Patient Characteristics Age (yrs)69( 12)65( 15)71( 10) 0.013 Gender Women, Men10273.06335.03938.0 0.07 Weight (kg)92.2( 23.4)90.6( 23.0)94.3( 23.7) 0.32 BSA (m2)2.3( 0.7)2.1( 0.7)2.4( 0.8) 0.56 Wall Thickness12.3( 3.1)9.2( 0.8)16.0( 2.4) 0.0001 Historical Information Prior CAD81(50.0%)41(41.8%)40(51.9%) 0.190 Prior Revascularization28(16.0%)10(10.2%)18(23.4%) 0.018 Hypertension112(64.0%)52(53.1%)60(77.9%) 0.0006 Diabetes Melitus51(29.1%)23(23.5%)28(36.4%) 0.063 Hyperlipidemia89(50.9%)46(46.9%)43(55.8%) 0.240 Smoking64(36.6%)31(31.6%)33(42.9%) 0.130 Asthma/COPD39(22.3%)16(16.3%)23(29.9%) 0.033 Medications Digoxin9(5.1%)6(6.1%)3(3.9%) 0.51 Vasodilator14(8.0%)7(7.1%)28(36.4%) 0.64 Diuretic60(34.3%)32(32.7%)28(36.4%) 0.61 Beta Blocker54(30.9%)23(23.5%)31(40.3%) 0.017 Calcium Antagonist32(18. 3%)13(13.3%)19(24.7%) 0.053 ASA82(46.9%)43(43.9%)39(50.6%) 0.38 Nitrate45(25.7%)20(20.4%)25(32.5%) 0.071 ACE Inhibitor39(22.3%)16(16.3%)23(29.9%) 0.033 Anti-Coagulation15(8.6%)4(4.1%)11(14.3%) 0.017 Statin65(37.1%)28(28.6%)37(48.1%) 0.0079 Abbreviations: ACE, angiotensin converting enzyme; ASA, aspirin, BSA; body surface ar ea; CAD, coronary artery disease; CHF, con gestive heart failure; COPD, chronic obstru ctive airways disease, LV EDWT, left ventricular end-diastolic wall thickness. Table 2: Hemodynamic dataHemodynamic DataTotalLV EDWTLV EDWT p v alue 12 mm>12 mm Rest Heart Rate (bpm)73 1873 1773 200.99 Systolic Blood Pressure (mmHg)136 38134 35138 430.48 Diastolic Blood Pressure (mmHg)76 2275 2077 250.48 Stress Heart Rate (bpm)129 28131 30126 270.30 Systolic Blood Pressure (mmHg)143 42143 40143 470.93 Diastolic Blood Pressure (mmHg)74 2473 2176 270.59 Abbreviations: bpm, blood pressure measur e; mmHg, millimeters of mercury; LV EDWT, le ft ventricular end-diastolic wall thicknes s.

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 5 of 9(page number not for citation purposes)prognosis, and thus often are not referred for aggressive risk management. Given the prevalence of risk factors such as hypertension, and an abnormal increase in LV EDWT in these patients, we felt it important to determine if the favorable prognosis in patients with a negative dobutamine stress test and a normal resting LV EDWT would occur in patients with a negative dobutamine stress test and an increase in resting LV EDWT. Our results indicate that in the absence of inducible LV WMA during intravenous dobutamine, either an average, a septal, or a posterior LV EDWT 12 mm measured in the 3-chamber (similar to echocardiographic parasternal long-axis view) using gradient-echo techniques was associated independently with future adverse cardiovascular events (Figure 2). Four possibilities could explain our results. First, with dobutamine stress echocardiography, previous investigators have noted an inability to visualize all myocardial wall segments during cardiac stress testing procedures [3,5], and thus one potentially can miss visualization of an inducible LV wall motion abnormality indicative of ischemia (a known risk factor for cardiac events) during intravenous dobutamine. For this reason, we utilized CMR because of previously reported high image quality and ability to assess both LV EDWT and WMA throughout the course of a dobutamine infusion [3-6]. In the current study, LV wall motion was visualized throughout the course of testing in all segments for all participants; and thus, inadvertently missing a stress induced LV wall motion abnormality due to suboptimal image quality is not felt to be the cause of the poor prognosis observed within the participants of the current study. Second, as shown in Table 1, the participants that experienced an increased incidence of cardiovascular events also exhibited many illnesses or clinical conditions, including hypertension, advanced age, prior coronary artery disease and diabetes, that have been associated previously with an adverse cardiac prognosis [11-14]. Importantly however,Table 3: Table of eventsTotalLV EDWTLV EDWT p -value 12 mm>12 mm Hard Events16(8.4%)3(3.2%)13(20.3%) 0.0015 Cardiac Deaths12(6.4%)3(3.2%)9(13.2%) 0.025 Myocardial Infarction4(2.2%)0(0.0%)4(5.5%) 0.022 Non Hard Event Hospital Admissions26(12%)12(12.2%)14(22.2%) 0.37 Congestive Hear t Failure2(1.1%)0(0.0%)2(2.7%) 0.11 Unstable-Angina24(13.1%)12(12.2%)12(15.6%) 0.4 Abbreviation: LV EDWT, left vent ricular end-diastolic wall thickness Kaplan-Meier survival curves for participants free from any cardiac event (Panel A), or a hard cardiac event (Panel B) Figure 2 Kaplan-Meier survival curves for participants free from any cardiac event (Panel A), or a hard cardiac event (Panel B) Graphs for individuals with and without LV end-diastolic wall thickness >12 mm are shown.

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 6 of 9(page number not for citation purposes)after serial adjustments utilizing multivariate models that included Framingham risk factors (age, gender, smoking, hypertension, elevated cholesterol) and other clinical conditions associated with adverse cardiac events, the presence of a LV EDWT 12 mm was a predictor of an adverse cardiac prognosis independent of the association that our participants may have had with known risk factors for adverse cardiac events. Thus, these analyses support the notion that LV EDWT is an independent risk factor, and that the poor prognosis identified in our participants was not due to confounding from a variable already known to be associated with adverse cardiovascular risk. Third, Smart, et al [7], have shown that in individuals with increased LV EDWT, the utility of dobutamine induced WMA for identifying inducible ischemia in patients with single vessel coronary artery disease is substantially reduced [7]. This is thought secondary to enhanced epicardial contraction in the thickened wall that can overcome the loss of contraction that may occur as endocardial tissue becomes ischemic during stress [7]. It Hazard ratios from multivariate analyses for average LV end-diastolic wall thickness >12 mm for any (Panel A) and hard (Panel B) cardiac events Figure 3 Hazard ratios from multivariate analyses for average LV end-diastolic wall thickness >12 mm for any (Panel A) and hard (Panel B) cardiac events As shown, the top row represents the unad justed Cox proportional hazard model, the second row represents the Cox proportional hazard model adjust ed for Framingham risk factors and the last row represents the Cox proportional hazard model adjusted for Framingham ri sk factors and other factors as sociated with cardiac events.

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 7 of 9(page number not for citation purposes)may be that our participants with increased LV EDWT exhibited myocardial ischemia in endocardial regions due to undiagnosed CAD. In turn, this unidentified inducible ischemia could have accounted for their future cardiac events. Addressing this point could occur with gadolinium enhanced first-pass dobutamine perfusion techniques [20]. Fourth, the presence of increased LV EDWT may portend a poor prognosis independent of the presence of coronary arteriosclerosis. Increases in LV EDWT can result from one or more of several factors including: increased LV afterload (due in part to increased vascular stiffness, factors influencing the neuro-hormonal axis (for example elevations of renin, angiotensin, or aldosterone), or preexisting genetic abnormalities [21,22]. Also, preclinical hypertrophic cardiomyopathy has been described [23]. Each of these variables in isolation or in combination with the other variables are associated with adverse cardiac events. In addition, their influence on the left ventricle promotes myocyte hypertrophy (often manifest as increased wall thickness) which is also an independent predictor of cardiac events [24]. Since we did not measure factors influencing the neuro-hormonal axis or assess genetic factors in the current study, we cannot comment on the potential influence of these variables on our outcomes. The findings of the current study have several important clinical implications for the management of patients with chest pain syndromes. First, the absence of dobutamine induced WMA in individuals with a resting left ventricular EDWT of 12 mm does not forecast the same cardiac prognosis as for individuals with a LV EDWT <12 mm. In fact, in the participants in this study with a LVEF >55% and no inducible LV WMA, the 2-year hard event free survival was 89%. In a previous study from our group that included patients referred for dobutamine stress that exhibited inducible ischemia and a LVEF >40%, the 2-year event free survival was 84% [5]. In short, in the setting of resting LV EDWT 12 mm and no inducible WMA, one should be concerned about not only the presence of undetected CAD (as noted by Smart, et al.)[7], but also that these individuals may have a poor cardiac prognosis relative to individuals with a wall thickness <12 mm. Second, further investigation should be considered to risk stratify patients with a LV EDWT >12 mm but without inducible WMA during intravenous dobutamine. Recently, Paetsch, et al [20], has demonstrated the utility of vasodilator first pass perfusion imaging in order to identify perfusion defects at the endocardial level associated with epicardial coronary artery stenoses. Additionally, in the setting of patients with hypertrophied ventricles or underlying CAD, Kwong et al.[25], and Moon et al [26], have shown recently that the presence of Late gadolinium enhancement is associated with fibrosis and an adverse cardiac prognosis. Third, it is important to recognize that we did not measure left ventricular mass in the current study. Thus, those individuals with eccentric left ventricular hypertrophy, who may have normal wall thickness, or those with concentric remodeling, who may or may not have an absolute increase in wall thickness depending upon their left ventricular cavity size, are not included in the current analyses. For this reason, these data are somewhat preliminary and further studies that would understand the relationship between left ventricular hypertrophy and the patterns of hypertrophy and adverse cardiovascular events are warranted. Fourth, the study was performed using measures of LV EDWT derived from cine, gradient-echo white blood imaging techniques. At 1.5 T, this image acquisition strategy often exhibits flow artifacts along the LV endocardial surface, particularly in apical views when LV systolic function is reduced. Though this technique has been used in large 6000 person population studies such as the MultiEthnic Study of Atherosclerosis [27], newer steady-state free precession cine white blood imaging techniques are more frequently used clinically. These data suggest similar studies should be performed that determine the prognostic importance of routine measures of heart size using steady-state free precession techniques. Our study has the following limitations. First, according to previously published criteria from transthoracic echocardiography, we selected a dichotomous variable of < or 12 mm in LV EDWT as our primary outcome variable [10]. Abnormal measures of LV EDWT have not been well established for gradient-echo or steady-state free precession CMR. These data suggest that future studies, similar to those performed with echocardiography, areTable 4: Multivariate predictors of events expressed as hazard ratio ( 95% confidence intervals)Multivariate CovariateCV Death/MIAny Event Age (Years)1.00 (0.97 1.03)1.05 (0.99 1.10) Hypertension1.32 (0.60 2.90)0.64 (0.17 2.35) Receiving Statin1.14 (0.58 2.25)0.56 (0.19 1.66) Diabetes1.79 (0.94 3.49)2.99 (0.94 9.56) Male Gender1.31 (0.69 2.48)2.88 (0.85 9.72) Prior CAD or Revasc.1.74 (0.9 0 3.37)1.58 (0.54 4.62) Smoking1.19 (0.63 2. 25)1.33 (0.47 3.77) Wall Thickness 122.34 (1.15 4.74)4.28 (1.1016.62) Abbreviations: CAD, coronary artery disease; Revasc., prior coronary artery revascularization procedure.

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Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 8 of 9(page number not for citation purposes)warranted to establish prognostic importance of routinely acquired CMR parameters of wall thickness. Although, the sample size was not large enough to have good power to detect moderate size effects, the observed hazard ratios of 6.0 for hard events and 3.0 for any events were large enough to demonstrate that there is a statistically (and clinically) significant increased risk of hard or any events with increased wall thickness. Second, measures of LV mass using a multi-slice short axis Simpson's Rule acquisition strategy were not acquired in the current study. Importantly however, our measures of LV EDWT are easily acquired and can be reported during echocardiographic as well as CMR techniques; hence the clinical applicability of this finding is high. Finally, we are unable to identify whether there is a threshold of LV EDWT that confers information regarding cardiac prognosis among individuals with different race [28]. The precision of the magnetic resonance data combined with the perfect longitudinal follow-up over 7 years allowed us to draw conclusions from a relatively small sample size, but the relevance of this measure across individuals of different race requires further study.ConclusionThese data indicate that in those with a LV ejection fraction >55% at rest and no inducible WMA during intravenous dobutamine, a LV EDWT measurement of 12 mm using cine white blood gradient-echo imaging techniques is associated with adverse cardiac events. Increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.AbbreviationsCAD: coronary heart disease; CHF: congestive heart failure; DCMR: dobutamine cardiovascular magnetic resonance; EDWT: end-diastolic wall thickness; HR: hazard ratio; LV: left ventricular; MI: myocardial infarction; USA: unstable angina; WMA: wall motion abnormalities.Competing interestsThe authors declare that funding for MRI image acquistions were in part supported by NIH R01HL074330 and NIH General Clinical Research Center M01RR07122 grants and through a small ownership in Prova, Inc., a company that produces and sells software for cardiac MRI image display.Authors' contributionsTFW performed follow-up, designed study and wrote manuscript; EDA performed follow-up, designed study, and wrote manuscript; TMM designed study, provided statistical analysis and edited manuscript; WN designed study and edited manuscript; KML performed MRI studies and image analysis, and edited manuscript; CAH enabled image acquisition and analysis, and edited manuscript; DWK designed study and edited manuscript; WGH designed study, performed MRI studies and image analysis, and edited manuscript.AcknowledgementsNorth Carolina Baptist Hospital Tech nology Development Fund (B-03-97/ 98); funded imaging exams National Institutes of Health R01HL074330; funded image analysis and investigator time The Claude D. Pepper Older American s Center, National Institutes of Health P30AG21332; and funded investigator time The National Institutes of Health General Clinical Research Center M01RR07122. funded image acquistionReferences1.Pennell DJ, Underwood SR, Manzar a CC, Swanton RH, Walker JM, Ell PJ, Longmore DB: Magnetic resonance imaging during dobutamine stress in coronary artery disease. Am J Cardiol 1992, 70(1): 34-40. 2.van Rugge FP, Wall EE van der, Spanjersberg SJ, de Roos A, Matheijssen NA, Zwinderman AH, van Dijkma n PR, Reiber JH, Bruschke AV: Magnetic resonance imaging during dobutamine stress for detection and localization of coronary artery disease: Quantitative wall motion analysis us ing a modification of the centerline method. Circulation 1994, 90(1): 127-38. 3.Hundley WG, Hamilton CA, Thomas MS, Herrington DM, Salido TB, Kitzman DW, Little WC, Link KM: Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography. Circulation 1999, 100: 1697-1702. 4.Nagel E, Lehmkuhl HB, Bocksch W, Klein C, Vogel U, Frantz E, Ellmer A, Dreysse S, Fleck E: Noninvasive diagno sis of ischemiainduced WMA with the use of high-dose dobutamine stress MRI: Comparison with dobu tamine stress echocardiography. Circulation 1999, 99: 763-70. 5.Hundley WG, Morgan TM, Neagle CM, Hamilton CA, Rerkpattanapipat P, Link KM: Magnetic resonance im aging determination of cardiac prognosis. Circulation 2002, 106: 2328-33. 6.Jahnke C, Nagel E, Gebker R, Koko cinski T, Kelle S, Manka R, Fleck E, Paetsch I: Prognostic value of card iac magnetic resonance stress tests: Adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation 2007, 115(13): 1769-76. 7.Smart SC, Knickelbine T, Malik F, Sagar KB: Dobutamine-atropine stress echocardiography for the detection of coronary artery disease in patients with left ventricular hypertrophy: Importance of chamber size and systolic wall stress. Circulation 2000, 10(3): 258-263. 8.Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC, Castelli WP: Echocardiographically dete cted left ventricular hypertrophy: Prevalence and risk factors. The Framington Heart Study, Ann Intern Med 1988, 108: 7-13. 9.Lawson MA, Blackwell GG, Davis ND Roney M, Dell' Italia LJ, Pohost GM: Accuracy of biplane long-a xis left ventricular volume

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Publish with Bio Med Central and every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright Submit your manuscript here:http://www.biomedcentral.com/info/publishing_adv.asp Bio Med central Journal of Cardiovascular Magnetic Resonance 2009, 11 :25http://www.jcmr-online.com/content/11/1/25 Page 9 of 9(page number not for citation purposes)determined by cine magnetic resonance imaging in patients with regional and global dysfunction. 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Ann Intern Med 1986, 105: 173-178. 20.Paetsch I, Jahnke C, Wahl A, Gebker R, Neuss M, Fleck E, Nagel E: Comparison of dobutamine stress magnetic resonance, adenosine stress magnetic resonance, and adenosine stress magnetic resonance perfusion. Circulation 2004, 110(7): 835-42. 21.Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP: Pathophysiological characterization of isol ated diastolic heart failure in comparison to systolic heart failure. JAMA 2002, 288(17): 2144-50. 22.Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M: EUROGENE Heart Failure Project. Hypert rophic cardiomyopathy: Distribution of disease genes, spec trum of mutations, and implications for a molecular diagnosis strategy. 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!DOCTYPE art SYSTEM 'http:www.biomedcentral.comxmlarticle.dtd'
ui 1532-429X-11-25
ji 1532-429X
fm
dochead Research
bibl
title
p Adverse effect of increased left ventricular wall thickness on five year outcomes of patients with negative dobutamine stress
aug
au ce yes id A1
snm Walsh
mi F
fnm Thomas
insr iid I1
email Thomas.Walsh@jax.ufl.edu
A2
Dall'Armellina
Erica
edallarme@gmail.com
A3
Chughtai
Haroon
eras_27@yahoo.com
A4
Morgan
M
Timothy
I2
tomorgan@wfubmc.edu
A5
Ntim
William
wntim@wfubmc.edu
A6
Link
M
Kerry
klink@wfubmc.edu
A7
Hamilton
A
Craig
I3
crhamilt@wfubmc.edu
A8
Kitzman
W
Dalane
dkitzman@wfubmc.edu
ca A9
Hundley
W Gregory
I4
ghundley@wfubmc.edu
insg
ins
Department of Internal Medicine (Cardiology Section), Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA
Division of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA
Department of Biomedical Engineering, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA
Department of Radiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA
source Journal of Cardiovascular Magnetic Resonance
issn 1532-429X
pubdate 2009
volume 11
issue 1
fpage 25
url http://www.jcmr-online.com/content/11/1/25
xrefbib
pubidlist
pubid idtype pmpid 19650895
doi 10.1186/1532-429X-11-25
history
rec
date
day 3
month 7
year 2008
acc
3
8
2009
pub
3
8
2009
cpyrt
2009
collab Walsh et al; licensee BioMed Central Ltd.
note This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
abs
sec
st
Abstract
Background
To determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis.
Results
Between 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction 55% without evidence of an inducible WMA during peak dobutamineatropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization./p
pIn a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT ≥12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization (HR 3.0, p = 0.0005)./p
/sec
sec
st
pConclusion/p
/st
pSimilar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted./p
/sec
/sec
/abs
/fm
bdy
sec
st
pBackground/p
/st
pLeft ventricular (LV) wall motion abnormalities (WMA) induced during intravenous dobutamine are associated with flow limiting epicardial coronary artery stenoses, and predict future cardiac events including myocardial infarction (MI) and cardiac death abbrgrpabbr bid="B1"1/abbrabbr bid="B2"2/abbrabbr bid="B3"3/abbrabbr bid="B4"4/abbr/abbrgrp. Typically, if resting LV end-diastolic wall thickness (EDWT) is normal, the absence of dobutamine inducible WMA identifies a group of individuals with a low risk of experiencing future cardiac events abbrgrpabbr bid="B5"5/abbrabbr bid="B6"6/abbr/abbrgrp. Importantly however, in individuals with increased resting LV EDWT, the sensitivity of dobutamine induced LV WMA for identifying flow limiting epicardial stenoses is low (36%) abbrgrpabbr bid="B7"7/abbr/abbrgrp. Also, data from Framingham have shown that increased LV EDWT itself is an independent predictor of cardiac events abbrgrpabbr bid="B8"8/abbr/abbrgrp. To date, it remains uncertain whether individuals with increased resting LV EDWT and an absence of inducible LV WMA during intravenous dobutamine remain at a relatively low risk of developing a future cardiac event./p
pThis study was performed to determine if the absence of inducible WMA during intravenous dobutamine would be associated with a favorable cardiac prognosis regardless of resting LV EDWT. To address this question, we measured LV EDWT and performed extensive follow-up on individuals undergoing dobutamine stress cardiovascular magnetic resonance (DCMR) examinations with cine white blood fast-gradient echo techniques./p
/sec
sec
st
pMethods/p
/st
sec
st
pPopulation and Study Design/p
/st
pThe study complies with the Declaration of Helsinki, and was approved by the Institutional Review Board at the Wake Forest University School of Medicine. All patients gave both verbal (for performing follow-up questionnaire) and written (for CMR and later for review of medical records) informed consent. Between 1997 and 2001, 175 consecutive participants with a LV ejection fraction 55%, and no inducible LV WMA indicative of ischemia in any of 17 myocardial segments during DCMR were enrolled in the study. After DCMR, participants blinded to DCMR test results performed the outcomes analysis.p
sec
sec
st
pDobutamineAtropine Cardiovascular Magnetic Resonancep
st
pAs previously described abbrgrpabbr bid="B3"3abbrabbr bid="B5"5abbrabbrgrp, images were obtained on a Horizon 1.5T whole-body imaging system (General Electric Medical Systems) using cine white blood spoiled gradient-echo imaging with a 256 × 128 matrix, a 35-48-cm field of view, a 4-ms echo time, a 10-ms repetition time, a 20-degree flip angle, an 8-mm slice thickness, a 40-ms temporal resolution, and 8 to 12 second periods of breath holding. Each of the patients received atropine if they were unable to obtain 80% maximum predicted heart rate for age (n = 95). Findings of this heart rate response have been shown at our institution to be 83% sensitive and 83% specific for identifying 50% coronary arterial luminal narrowings during dobutamineatropine stress, and have been shown to forecast future cardiac events abbrgrpabbr bid="B3"3abbrabbr bid="B5"5abbrabbrgrp.p
pAt rest and during graded doses of dobutamineatropine stress, LV wall motion was confirmed as normal across all 17 myocardial segments abbrgrpabbr bid="B5"5abbrabbrgrp. The resting LV ejection fraction was measured using a biplane area-length technique abbrgrpabbr bid="B9"9abbrabbrgrp. According to previously published techniques, the posterior and septal wall thicknesses were measured at the level of the LV minor dimension, at the mitral chordae level using the end-diastolic, left ventricular 3-chamber (equivalent to transthoracic echocardiography parasternal long-axis) view (Figure figr fid="F1"1figr) abbrgrpabbr bid="B10"10abbrabbrgrp. At the time of testing, the occurrence of a prior Q-wave myocardial infarction abbrgrpabbr bid="B11"11abbrabbrgrp, and the presence of cardiac risk factors [including a history of diabetes abbrgrpabbr bid="B12"12abbrabbrgrp, smoking, coronary revascularization, elevated total cholesterol abbrgrpabbr bid="B13"13abbrabbrgrp, and hypertension abbrgrpabbr bid="B14"14abbrabbrgrp were recorded.p
fig id="F1"
title
pFigure 1p
title
caption
pIn accordance with the American Society of Echocardiography, posterior (green line) and septal (red line) left ventricular wall thickness was measured in the left ventricular long axis view at end diastole at approximately the level of the mitral valve leaflet tips (LV = left ventricle; LA = left atrium; and Ao = aorta)p
caption
text
pbIn accordance with the American Society of Echocardiography, posterior (green line) and septal (red line) left ventricular wall thickness was measured in the left ventricular long axis view at end diastole at approximately the level of the mitral valve leaflet tips (LV = left ventricle; LA = left atrium; and Ao = aorta)b.p
text
graphic file="1532-429X-11-25-1"
fig
sec
sec
st
pOutcomesp
st
pWithin 7 years of the DCMR exam, each participant was contacted to determine the post-procedure occurrence of cardiac events. All persons were contacted initially by phone or personal interview. If deceased, the next of kin was contacted. Questions were administered to identify the possibility of myocardial infarction (MI), unstable angina (USA) or congestive heart failure (CHF). Any change in physical state, medical condition, or medicationwas confirmed in all cases by review of the participant's medical records. If an event was suspected or identified during contact with the participant, medical records from the site of the event were obtained and confirmation of the event was determined according to data collected from the medical record. Established, published criteria were utilized to define events. Hard events were defined as cardiac death (death in the presenceof acute MI, significant cardiac arrhythmia, or refractory CHF abbrgrpabbr bid="B15"15abbrabbrgrp, or MI (angina of 30 minutes durationand either ≥ 2 mm ST segment elevation in 2 consecutive ECG leadsor a rise in cardiac enzymes including creatine kinase level MB fraction cardiac troponin-I above normal limits) abbrgrpabbr bid="B16"16abbrabbrgrp. Electrocardiographic, enzymatic, or autopsy data were used tosubstantiate cardiac mortality. Any events were defined as hard events andor USA, or CHF warranting hospital admission. In the case of 2 simultaneouscardiac events, the worst event was chosen (cardiac deathMI USACHF).p
sec
sec
st
pStatistical Analysisp
st
pAfter all records were obtained, a statistical analysis was conducted using SAS 9.1 (SAS Institute, Cary, NC) for Windows. Based on previously published criteria, participants were dichotomized into those with a LV EDWT < or ≥12 mm abbrgrpabbr bid="B15"15abbrabbrgrp. In this study, we determined LV EDWT in the septum, posterior wall, and the average of the two. The average LV EDWT of the septal and posterior walls served as the primary outcome measure. All grouped data were expressed as mean ± SD. Independent predictors of events were identified using univariate and multivariate Cox proportional hazards regression models. The risk of a given variable was expressed by a hazard ratio (HR) with corresponding 95% CIs. A variable was considered significant if the null hypothesis of no contribution could be rejected at a probability value of <0.05. The probability of the presence or absence of hard events as a function of follow-up duration was estimated by the Kaplan-Meier method and compared between groups by use of the log-rank test. Unadjusted, Framingham adjusted, and additional cardiac MI risk factor adjusted Cox proportional hazard regression models were used to predict cardiac events.p
pTo determine the intra observer variability for measuring LV EDWT, a randomly selected sample of 20 participants was analyzed twice separated by 1 year. To determine inter observer agreement in measures of LV EDWT, this same sample from 20 participants was analyzed by a separate individual. In both the intra and inter observer comparisons, repeat assessments were performed in an unpaired fashion blinded to the results of prior analyses.p
pThe authors had full access to the data and take responsibility for its integrity.p
sec
sec
sec
st
pResultsp
st
pContact was made with all 175 patients; their clinical data are displayed in Table tblr tid="T1"1tblr. Those with an average (septal and posterior wall) LV EDWT ≥12 mm were older, and exhibited more prior CAD, hypertension, diabetes, and lung disease. Overall, the amount of dobutamine administered was 30 ± 10 μgkgmin and did not differ between those with and without a LV EDWT < or ≥12 mm. Rest and stress hemodynamic assessments at the time of DCMR stress were similar for those with or without LV EDWT < or ≥12 mm (Table tblr tid="T2"2tblr).p
tbl id="T1"
title
pTable 1p
title
caption
pDemographic datap
caption
tblbdy cols="8"
r
c
p
c
c
p
c
c
p
c
c ca="left" cspan="2"
pLV EDWTp
c
c ca="left" cspan="2"
pLV EDWTp
c
c ca="left"
pitpit-valuep
c
r
r
c
p
c
c cspan="6"
hr
c
c
p
c
r
r
c
p
c
c ca="left"
pTotalp
c
c
p
c
c ca="left"
p≤12 mmp
c
c
p
c
c ca="left"
p12 mmp
c
c
p
c
c
p
c
r
r
c
p
c
c cspan="6"
hr
c
c
p
c
r
r
c
p
c
c ca="center" cspan="2"
pn = 175p
c
c ca="center" cspan="2"
pn = 98p
c
c ca="center" cspan="2"
pn = 77p
c
c
p
c
r
r
c cspan="8"
hr
c
r
r
c ca="left"
pPatient Characteristicsp
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
r
r
c ca="left" indent="1"
pAge (yrs)p
c
c ca="left"
p69p
c
c ca="left"
p(± 12)p
c
c ca="left"
p65p
c
c ca="left"
p(± 15)p
c
c ca="left"
p71p
c
c ca="left"
p(± 10)p
c
c ca="left"
p
it0.013it
p
c
r
r
c ca="left" indent="1"
pGender Women, Menp
c
c ca="left"
p102p
c
c ca="left"
p73.0p
c
c ca="left"
p63p
c
c ca="left"
p35.0p
c
c ca="left"
p39p
c
c ca="left"
p38.0p
c
c ca="left"
p
it0.07it
p
c
r
r
c ca="left" indent="1"
pWeight (kg)p
c
c ca="left"
p92.2p
c
c ca="left"
p(± 23.4)p
c
c ca="left"
p90.6p
c
c ca="left"
p(± 23.0)p
c
c ca="left"
p94.3p
c
c ca="left"
p(± 23.7)p
c
c ca="left"
p
it0.32it
p
c
r
r
c ca="left" indent="1"
pBSA (msup2sup)p
c
c ca="left"
p2.3p
c
c ca="left"
p(± 0.7)p
c
c ca="left"
p2.1p
c
c ca="left"
p(± 0.7)p
c
c ca="left"
p2.4p
c
c ca="left"
p(± 0.8)p
c
c ca="left"
p
it0.56it
p
c
r
r
c ca="left" indent="1"
pWall Thicknessp
c
c ca="left"
p12.3p
c
c ca="left"
p(± 3.1)p
c
c ca="left"
p9.2p
c
c ca="left"
p(± 0.8)p
c
c ca="left"
p16.0p
c
c ca="left"
p(± 2.4)p
c
c ca="left"
p
it0.0001it
p
c
r
r
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
r
r
c ca="left"
pHistorical Informationp
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
r
r
c ca="left" indent="1"
pPrior CADp
c
c ca="left"
p81p
c
c ca="left"
p(50.0%)p
c
c ca="left"
p41p
c
c ca="left"
p(41.8%)p
c
c ca="left"
p40p
c
c ca="left"
p(51.9%)p
c
c ca="left"
p
it0.190it
p
c
r
r
c ca="left" indent="1"
pPrior Revascularizationp
c
c ca="left"
p28p
c
c ca="left"
p(16.0%)p
c
c ca="left"
p10p
c
c ca="left"
p(10.2%)p
c
c ca="left"
p18p
c
c ca="left"
p(23.4%)p
c
c ca="left"
p
it0.018it
p
c
r
r
c ca="left" indent="1"
pHypertensionp
c
c ca="left"
p112p
c
c ca="left"
p(64.0%)p
c
c ca="left"
p52p
c
c ca="left"
p(53.1%)p
c
c ca="left"
p60p
c
c ca="left"
p(77.9%)p
c
c ca="left"
p
it0.0006it
p
c
r
r
c ca="left" indent="1"
pDiabetes Melitusp
c
c ca="left"
p51p
c
c ca="left"
p(29.1%)p
c
c ca="left"
p23p
c
c ca="left"
p(23.5%)p
c
c ca="left"
p28p
c
c ca="left"
p(36.4%)p
c
c ca="left"
p
it0.063it
p
c
r
r
c ca="left" indent="1"
pHyperlipidemiap
c
c ca="left"
p89p
c
c ca="left"
p(50.9%)p
c
c ca="left"
p46p
c
c ca="left"
p(46.9%)p
c
c ca="left"
p43p
c
c ca="left"
p(55.8%)p
c
c ca="left"
p
it0.240it
p
c
r
r
c ca="left" indent="1"
pSmokingp
c
c ca="left"
p64p
c
c ca="left"
p(36.6%)p
c
c ca="left"
p31p
c
c ca="left"
p(31.6%)p
c
c ca="left"
p33p
c
c ca="left"
p(42.9%)p
c
c ca="left"
p
it0.130it
p
c
r
r
c ca="left" indent="1"
pAsthmaCOPDp
c
c ca="left"
p39p
c
c ca="left"
p(22.3%)p
c
c ca="left"
p16p
c
c ca="left"
p(16.3%)p
c
c ca="left"
p23p
c
c ca="left"
p(29.9%)p
c
c ca="left"
p
it0.033it
p
c
r
r
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
r
r
c ca="left"
pMedicationsp
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
r
r
c ca="left" indent="1"
pDigoxinp
c
c ca="left"
p9p
c
c ca="left"
p(5.1%)p
c
c ca="left"
p6p
c
c ca="left"
p(6.1%)p
c
c ca="left"
p3p
c
c ca="left"
p(3.9%)p
c
c ca="left"
p
it0.51it
p
c
r
r
c ca="left" indent="1"
pVasodilatorp
c
c ca="left"
p14p
c
c ca="left"
p(8.0%)p
c
c ca="left"
p7p
c
c ca="left"
p(7.1%)p
c
c ca="left"
p28p
c
c ca="left"
p(36.4%)p
c
c ca="left"
p
it0.64it
p
c
r
r
c ca="left" indent="1"
pDiureticp
c
c ca="left"
p60p
c
c ca="left"
p(34.3%)p
c
c ca="left"
p32p
c
c ca="left"
p(32.7%)p
c
c ca="left"
p28p
c
c ca="left"
p(36.4%)p
c
c ca="left"
p
it0.61it
p
c
r
r
c ca="left" indent="1"
pBeta Blockerp
c
c ca="left"
p54p
c
c ca="left"
p(30.9%)p
c
c ca="left"
p23p
c
c ca="left"
p(23.5%)p
c
c ca="left"
p31p
c
c ca="left"
p(40.3%)p
c
c ca="left"
p
it0.017it
p
c
r
r
c ca="left" indent="1"
pCalcium Antagonistp
c
c ca="left"
p32p
c
c ca="left"
p(18.3%)p
c
c ca="left"
p13p
c
c ca="left"
p(13.3%)p
c
c ca="left"
p19p
c
c ca="left"
p(24.7%)p
c
c ca="left"
p
it0.053it
p
c
r
r
c ca="left" indent="1"
pASAp
c
c ca="left"
p82p
c
c ca="left"
p(46.9%)p
c
c ca="left"
p43p
c
c ca="left"
p(43.9%)p
c
c ca="left"
p39p
c
c ca="left"
p(50.6%)p
c
c ca="left"
p
it0.38it
p
c
r
r
c ca="left" indent="1"
pNitratep
c
c ca="left"
p45p
c
c ca="left"
p(25.7%)p
c
c ca="left"
p20p
c
c ca="left"
p(20.4%)p
c
c ca="left"
p25p
c
c ca="left"
p(32.5%)p
c
c ca="left"
p
it0.071it
p
c
r
r
c ca="left" indent="1"
pACE Inhibitorp
c
c ca="left"
p39p
c
c ca="left"
p(22.3%)p
c
c ca="left"
p16p
c
c ca="left"
p(16.3%)p
c
c ca="left"
p23p
c
c ca="left"
p(29.9%)p
c
c ca="left"
p
it0.033it
p
c
r
r
c ca="left" indent="1"
pAnti-Coagulationp
c
c ca="left"
p15p
c
c ca="left"
p(8.6%)p
c
c ca="left"
p4p
c
c ca="left"
p(4.1%)p
c
c ca="left"
p11p
c
c ca="left"
p(14.3%)p
c
c ca="left"
p
it0.017it
p
c
r
r
c ca="left" indent="1"
pStatinp
c
c ca="left"
p65p
c
c ca="left"
p(37.1%)p
c
c ca="left"
p28p
c
c ca="left"
p(28.6%)p
c
c ca="left"
p37p
c
c ca="left"
p(48.1%)p
c
c ca="left"
p
it0.0079it
p
c
r
tblbdy
tblfn
pAbbreviations: ACE, angiotensin converting enzyme; ASA, aspirin, BSA; body surface area; CAD, coronary artery disease; CHF, congestive heart failure; COPD, chronic obstructive airways disease, LV EDWT, left ventricular end-diastolic wall thickness.p
tblfn
tbl
tbl id="T2"
title
pTable 2p
title
caption
pHemodynamic datap
caption
tblbdy cols="5"
r
c ca="left"
pHemodynamic Datap
c
c ca="left"
pTotalp
c
c ca="left"
pLV EDWTp
c
c ca="left"
pLV EDWTp
c
c ca="left"
pitpit-itvitaluep
c
r
r
c
p
c
c cspan="3"
hr
c
c
p
c
r
r
c
p
c
c ca="left"
p≤12 mmp
c
c
p
c
c ca="left"
p12 mmp
c
c
p
c
r
r
c
p
c
c cspan="3"
hr
c
c
p
c
r
r
c
p
c
c ca="left"
pRestp
c
c
p
c
c
p
c
c
p
c
r
r
c cspan="5"
hr
c
r
r
c ca="left"
pHeart Rate (bpm)p
c
c ca="left"
p73 ± 18p
c
c ca="left"
p73 ± 17p
c
c ca="left"
p73 ± 20p
c
c ca="left"
p0.99p
c
r
r
c ca="left"
pSystolic Blood Pressure (mmHg)p
c
c ca="left"
p136 ± 38p
c
c ca="left"
p134 ± 35p
c
c ca="left"
p138 ± 43p
c
c ca="left"
p0.48p
c
r
r
c ca="left"
pDiastolic Blood Pressure (mmHg)p
c
c ca="left"
p76 ± 22p
c
c ca="left"
p75 ± 20p
c
c ca="left"
p77 ± 25p
c
c ca="left"
p0.48p
c
r
r
c cspan="5"
hr
c
r
r
c
p
c
c ca="left"
pStressp
c
c
p
c
c
p
c
c
p
c
r
r
c cspan="5"
hr
c
r
r
c ca="left"
pHeart Rate (bpm)p
c
c ca="left"
p129 ± 28p
c
c ca="left"
p131 ± 30p
c
c ca="left"
p126 ± 27p
c
c ca="left"
p0.30p
c
r
r
c ca="left"
pSystolic Blood Pressure (mmHg)p
c
c ca="left"
p143 ± 42p
c
c ca="left"
p143 ± 40p
c
c ca="left"
p143 ± 47p
c
c ca="left"
p0.93p
c
r
r
c ca="left"
pDiastolic Blood Pressure (mmHg)p
c
c ca="left"
p74 ± 24p
c
c ca="left"
p73 ± 21p
c
c ca="left"
p76 ± 27p
c
c ca="left"
p0.59p
c
r
tblbdy
tblfn
pAbbreviations: bpm, blood pressure measure; mmHg, millimeters of mercury; LV EDWT, left ventricular end-diastolic wall thickness.p
tblfn
tbl
pOver the 5.5 average years of follow-up, the rate of hard events was 8.4% (Table tblr tid="T3"3tblr). The 5.5 year hard event rate was 3.2% for the patients with a LV EDWT <12 mm compared to 20.3% for those with a LV EDWT ≥12 mm. The EDWT for the posterior wall averaged 12 ± 3 mm in participants with no events, and 14 ± 3 mm in participants with any events (p < 0.001). Similarly, the septal wall thickness in patients without events was 12 ± 3 mm compared to 14 ± 4 mm for those with any events (p < 0.001). The septal and posterior wall thickness among the participants were highly correlated (r = 0.76, p = 0.001). There was no difference in the predictive accuracy of the septal, posterior, or combined average of the wall thickness for identifying those at risk of future cardiac events.p
tbl id="T3"
title
pTable 3p
title
caption
pTable of eventsp
caption
tblbdy cols="8"
r
c
p
c
c
p
c
c ca="left"
pTotalp
c
c ca="center" cspan="2"
pLV EDWTp
c
c ca="center" cspan="2"
pLV EDWTp
c
c ca="left"
pitpit-valuep
c
r
r
c
p
c
c cspan="6"
hr
c
c
p
c
r
r
c
p
c
c
p
c
c
p
c
c ca="left" cspan="2"
p≤12 mmp
c
c ca="left" cspan="2"
p12 mmp
c
c
p
c
r
r
c cspan="8"
hr
c
r
r
c ca="left"
pHard Eventsp
c
c ca="left"
p16p
c
c ca="left"
p(8.4%)p
c
c ca="left"
p3p
c
c ca="left"
p(3.2%)p
c
c ca="left"
p13p
c
c ca="left"
p(20.3%)p
c
c ca="left"
p
it0.0015it
p
c
r
r
c ca="left" indent="1"
pCardiac Deathsp
c
c ca="left"
p12p
c
c ca="left"
p(6.4%)p
c
c ca="left"
p3p
c
c ca="left"
p(3.2%)p
c
c ca="left"
p9p
c
c ca="left"
p(13.2%)p
c
c ca="left"
p
it0.025it
p
c
r
r
c ca="left" indent="1"
pMyocardial Infarctionp
c
c ca="left"
p4p
c
c ca="left"
p(2.2%)p
c
c ca="left"
p0p
c
c ca="left"
p(0.0%)p
c
c ca="left"
p4p
c
c ca="left"
p(5.5%)p
c
c ca="left"
p
it0.022it
p
c
r
r
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
c
p
c
r
r
c ca="left"
pNon Hard Event Hospital Admissionsp
c
c ca="left"
p26p
c
c ca="left"
p(12%)p
c
c ca="left"
p12p
c
c ca="left"
p(12.2%)p
c
c ca="left"
p14p
c
c ca="left"
p(22.2%)p
c
c ca="left"
p
it0.37it
p
c
r
r
c ca="left" indent="1"
pCongestive Heart Failurep
c
c ca="left"
p2p
c
c ca="left"
p(1.1%)p
c
c ca="left"
p0p
c
c ca="left"
p(0.0%)p
c
c ca="left"
p2p
c
c ca="left"
p(2.7%)p
c
c ca="left"
p
it0.11it
p
c
r
r
c ca="left" indent="1"
pUnstable-Anginap
c
c ca="left"
p24p
c
c ca="left"
p(13.1%)p
c
c ca="left"
p12p
c
c ca="left"
p(12.2%)p
c
c ca="left"
p12p
c
c ca="left"
p(15.6%)p
c
c ca="left"
p
it0.4it
p
c
r
tblbdy
tblfn
pAbbreviation: LV EDWT, left ventricular end-diastolic wall thicknessp
tblfn
tbl
pThe proportion of participants free of both hard and any cardiac events is shown in Figure figr fid="F2"2figr. A LV EDWT ≥12 mm was predictive of both any and hard events in a) the unadjusted model, b) the Framingham risk factor adjusted model, and c) after adjustment for factors associated with CAD, MI, and cardiac events (Figure figr fid="F3"3figr and Table tblr tid="T4"4tblr). We also performed analyses treating LV EDWT as a continuous, as opposed to dichotomous (< or ≥12 mm thick) variable. Using the proportional hazard wall thickness as a continuous variable demonstrated a significant trend of increasing risk of hard events (p = 0.004) and any events (p = 0.001) with increasing LV EDWT.p
fig id="F2"
title
pFigure 2p
title
caption
pKaplan-Meier survival curves for participants free from any cardiac event (Panel A), or a hard cardiac event (Panel B)p
caption
text
pbKaplan-Meier survival curves for participants free from any cardiac event (Panel A), or a hard cardiac event (Panel B)b. Graphs for individuals with and without LV end-diastolic wall thickness 12 mm are shown.p
text
graphic file="1532-429X-11-25-2"
fig
fig id="F3"
title
pFigure 3p
title
caption
pHazard ratios from multivariate analyses for average LV end-diastolic wall thickness 12 mm for any (Panel A) and hard (Panel B) cardiac eventsp
caption
text
pbHazard ratios from multivariate analyses for average LV end-diastolic wall thickness 12 mm for any (Panel A) and hard (Panel B) cardiac eventsb. As shown, the top row represents the unadjusted Cox proportional hazard model, the second row represents the Cox proportional hazard model adjusted for Framingham risk factors, and the last row represents the Cox proportional hazard model adjusted for Framingham risk factors and other factors associated with cardiac events.p
text
graphic file="1532-429X-11-25-3"
fig
tbl id="T4"
title
pTable 4p
title
caption
pMultivariate predictors of events expressed as hazard ratio (± 95% confidence intervals)p
caption
tblbdy cols="3"
r
c
p
c
c ca="center" cspan="2"
p
bMultivariateb
p
c
r
r
c ca="left"
p
bCovariateb
p
c
c ca="center"
p
bCV DeathMIb
p
c
c ca="center"
p
bAny Eventb
p
c
r
r
c cspan="3"
hr
c
r
r
c ca="left"
pAge (Years)p
c
c ca="center"
p1.00 (0.97 1.03)p
c
c ca="center"
p1.05 (0.99 1.10)p
c
r
r
c ca="left"
pHypertensionp
c
c ca="center"
p1.32 (0.60 2.90)p
c
c ca="center"
p0.64 (0.17 2.35)p
c
r
r
c ca="left"
pReceiving Statinp
c
c ca="center"
p1.14 (0.58 2.25)p
c
c ca="center"
p0.56 (0.19 1.66)p
c
r
r
c ca="left"
pDiabetesp
c
c ca="center"
p1.79 (0.94 3.49)p
c
c ca="center"
p2.99 (0.94 9.56)p
c
r
r
c ca="left"
pMale Genderp
c
c ca="center"
p1.31 (0.69 2.48)p
c
c ca="center"
p2.88 (0.85 9.72)p
c
r
r
c ca="left"
pPrior CAD or Revasc.p
c
c ca="center"
p1.74 (0.90 3.37)p
c
c ca="center"
p1.58 (0.54 4.62)p
c
r
r
c ca="left"
pSmokingp
c
c ca="center"
p1.19 (0.63 2.25)p
c
c ca="center"
p1.33 (0.47 3.77)p
c
r
r
c ca="left"
pWall Thickness ≥ 12p
c
c ca="center"
p2.34 (1.15 4.74)p
c
c ca="center"
p4.28 (1.10-16.62)p
c
r
tblbdy
tblfn
pAbbreviations: CAD, coronary artery disease; Revasc., prior coronary artery revascularization procedure.p
tblfn
tbl
pThe intra observer correlation of LV EDWT was 0.73, and the inter observer assessment of LV EDWT was 0.77.p
sec
sec
st
pDiscussionp
st
pPrior studies have found that increased LV EDWT during a dobutamine stress test is associated with a decreased sensitivity for detecting flow limiting coronary arterial luminal narrowings detected with contrast coronary angiography abbrgrpabbr bid="B7"7abbrabbrgrp. Other studies have identified an association between the presence of LV hypertrophy or increased LV EDWT and an adverse cardiac prognosis abbrgrpabbr bid="B8"8abbrabbr bid="B17"17abbrabbr bid="B18"18abbrabbr bid="B19"19abbrabbrgrp. In many countries, dobutamine stress echocardiography is performed widely for individuals suspected to have or possessing coronary arteriosclerosis, MI, or CHF. Individuals without inducible LV WMA are ascribed a favorable prognosis, and thus often are not referred for aggressive risk management. Given the prevalence of risk factors such as hypertension, and an abnormal increase in LV EDWT in these patients, we felt it important to determine if the favorable prognosis in patients with a negative dobutamine stress test and a normal resting LV EDWT would occur in patients with a negative dobutamine stress test and an increase in resting LV EDWT. Our results indicate that in the absence of inducible LV WMA during intravenous dobutamine, either an average, a septal, or a posterior LV EDWT ≥12 mm measured in the 3-chamber (similar to echocardiographic parasternal long-axis view) using gradient-echo techniques was associated independently with future adverse cardiovascular events (Figure figr fid="F2"2figr).p
pFour possibilities could explain our results. First, with dobutamine stress echocardiography, previous investigators have noted an inability to visualize all myocardial wall segments during cardiac stress testing procedures abbrgrpabbr bid="B3"3abbrabbr bid="B5"5abbrabbrgrp, and thus one potentially can miss visualization of an inducible LV wall motion abnormality indicative of ischemia (a known risk factor for cardiac events) during intravenous dobutamine. For this reason, we utilized CMR because of previously reported high image quality and ability to assess both LV EDWT and WMA throughout the course of a dobutamine infusion abbrgrpabbr bid="B3"3abbrabbr bid="B4"4abbrabbr bid="B5"5abbrabbr bid="B6"6abbrabbrgrp. In the current study, LV wall motion was visualized throughout the course of testing in all segments for all participants; and thus, inadvertently missing a stress induced LV wall motion abnormality due to suboptimal image quality is not felt to be the cause of the poor prognosis observed within the participants of the current study.p
pSecond, as shown in Table tblr tid="T1"1tblr, the participants that experienced an increased incidence of cardiovascular events also exhibited many illnesses or clinical conditions, including hypertension, advanced age, prior coronary artery disease and diabetes, that have been associated previously with an adverse cardiac prognosis abbrgrpabbr bid="B11"11abbrabbr bid="B12"12abbrabbr bid="B13"13abbrabbr bid="B14"14abbrabbrgrp. Importantly however, after serial adjustments utilizing multivariate models that included Framingham risk factors (age, gender, smoking, hypertension, elevated cholesterol) and other clinical conditions associated with adverse cardiac events, the presence of a LV EDWT ≥12 mm was a predictor of an adverse cardiac prognosis independent of the association that our participants may have had with known risk factors for adverse cardiac events. Thus, these analyses support the notion that LV EDWT is an independent risk factor, and that the poor prognosis identified in our participants was not due to confounding from a variable already known to be associated with adverse cardiovascular risk.p
pThird, Smart, et al abbrgrpabbr bid="B7"7abbrabbrgrp, have shown that in individuals with increased LV EDWT, the utility of dobutamine induced WMA for identifying inducible ischemia in patients with single vessel coronary artery disease is substantially reduced abbrgrpabbr bid="B7"7abbrabbrgrp. This is thought secondary to enhanced epicardial contraction in the thickened wall that can overcome the loss of contraction that may occur as endocardial tissue becomes ischemic during stress abbrgrpabbr bid="B7"7abbrabbrgrp. It may be that our participants with increased LV EDWT exhibited myocardial ischemia in endocardial regions due to undiagnosed CAD. In turn, this unidentified inducible ischemia could have accounted for their future cardiac events. Addressing this point could occur with gadolinium enhanced first-pass dobutamine perfusion techniques abbrgrpabbr bid="B20"20abbrabbrgrp.p
pFourth, the presence of increased LV EDWT may portend a poor prognosis independent of the presence of coronary arteriosclerosis. Increases in LV EDWT can result from one or more of several factors including: increased LV afterload (due in part to increased vascular stiffness, factors influencing the neuro-hormonal axis (for example elevations of renin, angiotensin, or aldosterone), or preexisting genetic abnormalities abbrgrpabbr bid="B21"21abbrabbr bid="B22"22abbrabbrgrp. Also, preclinical hypertrophic cardiomyopathy has been described abbrgrpabbr bid="B23"23abbrabbrgrp. Each of these variables in isolation or in combination with the other variables are associated with adverse cardiac events. In addition, their influence on the left ventricle promotes myocyte hypertrophy (often manifest as increased wall thickness) which is also an independent predictor of cardiac events abbrgrpabbr bid="B24"24abbrabbrgrp. Since we did not measure factors influencing the neuro-hormonal axis or assess genetic factors in the current study, we cannot comment on the potential influence of these variables on our outcomes.p
pThe findings of the current study have several important clinical implications for the management of patients with chest pain syndromes. First, the absence of dobutamine induced WMA in individuals with a resting left ventricular EDWT of ≥12 mm does not forecast the same cardiac prognosis as for individuals with a LV EDWT <12 mm. In fact, in the participants in this study with a LVEF 55% and no inducible LV WMA, the 2-year hard event free survival was 89%. In a previous study from our group that included patients referred for dobutamine stress that exhibited inducible ischemia and a LVEF 40%, the 2-year event free survival was 84% abbrgrpabbr bid="B5"5abbrabbrgrp. In short, in the setting of resting LV EDWT ≥12 mm and no inducible WMA, one should be concerned about not only the presence of undetected CAD (as noted by Smart, et al.)abbrgrpabbr bid="B7"7abbrabbrgrp, but also that these individuals may have a poor cardiac prognosis relative to individuals with a wall thickness <12 mm.p
pSecond, further investigation should be considered to risk stratify patients with a LV EDWT 12 mm but without inducible WMA during intravenous dobutamine. Recently, Paetsch, et al abbrgrpabbr bid="B20"20abbrabbrgrp, has demonstrated the utility of vasodilator first pass perfusion imaging in order to identify perfusion defects at the endocardial level associated with epicardial coronary artery stenoses. Additionally, in the setting of patients with hypertrophied ventricles or underlying CAD, Kwong et al.abbrgrpabbr bid="B25"25abbrabbrgrp, and Moon et al abbrgrpabbr bid="B26"26abbrabbrgrp, have shown recently that the presence of Late gadolinium enhancement is associated with fibrosis and an adverse cardiac prognosis.p
pThird, it is important to recognize that we did not measure left ventricular mass in the current study. Thus, those individuals with eccentric left ventricular hypertrophy, who may have normal wall thickness, or those with concentric remodeling, who may or may not have an absolute increase in wall thickness depending upon their left ventricular cavity size, are not included in the current analyses. For this reason, these data are somewhat preliminary and further studies that would understand the relationship between left ventricular hypertrophy and the patterns of hypertrophy and adverse cardiovascular events are warranted.p
pFourth, the study was performed using measures of LV EDWT derived from cine, gradient-echo white blood imaging techniques. At 1.5 T, this image acquisition strategy often exhibits flow artifacts along the LV endocardial surface, particularly in apical views when LV systolic function is reduced. Though this technique has been used in large 6000 person population studies such as the Multi-Ethnic Study of Atherosclerosis abbrgrpabbr bid="B27"27abbrabbrgrp, newer steady-state free precession cine white blood imaging techniques are more frequently used clinically. These data suggest similar studies should be performed that determine the prognostic importance of routine measures of heart size using steady-state free precession techniques.p
pOur study has the following limitations. First, according to previously published criteria from transthoracic echocardiography, we selected a dichotomous variable of < or ≥12 mm in LV EDWT as our primary outcome variable abbrgrpabbr bid="B10"10abbrabbrgrp. Abnormal measures of LV EDWT have not been well established for gradient-echo or steady-state free precession CMR. These data suggest that future studies, similar to those performed with echocardiography, are warranted to establish prognostic importance of routinely acquired CMR parameters of wall thickness. Although, the sample size was not large enough to have good power to detect moderate size effects, the observed hazard ratios of 6.0 for hard events and 3.0 for any events were large enough to demonstrate that there is a statistically (and clinically) significant increased risk of hard or any events with increased wall thickness.p
pSecond, measures of LV mass using a multi-slice short axis Simpson's Rule acquisition strategy were not acquired in the current study. Importantly however, our measures of LV EDWT are easily acquired and can be reported during echocardiographic as well as CMR techniques; hence the clinical applicability of this finding is high. Finally, we are unable to identify whether there is a threshold of LV EDWT that confers information regarding cardiac prognosis among individuals with different race abbrgrpabbr bid="B28"28abbrabbrgrp. The precision of the magnetic resonance data combined with the perfect longitudinal follow-up over 7 years allowed us to draw conclusions from a relatively small sample size, but the relevance of this measure across individuals of different race requires further study.p
sec
sec
st
pConclusionp
st
pThese data indicate that in those with a LV ejection fraction 55% at rest and no inducible WMA during intravenous dobutamine, a LV EDWT measurement of ≥12 mm using cine white blood gradient-echo imaging techniques is associated with adverse cardiac events. Increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.p
sec
sec
st
pAbbreviationsp
st
pCAD: coronary heart disease; CHF: congestive heart failure; DCMR: dobutamine cardiovascular magnetic resonance; EDWT: end-diastolic wall thickness; HR: hazard ratio; LV: left ventricular; MI: myocardial infarction; USA: unstable angina; WMA: wall motion abnormalities.p
sec
sec
st
pCompeting interestsp
st
pThe authors declare that funding for MRI image acquistions were in part supported by NIH R01HL074330 and NIH General Clinical Research Center M01RR07122 grants and through a small ownership in Prova, Inc., a company that produces and sells software for cardiac MRI image display.p
sec
sec
st
pAuthors' contributionsp
st
pTFW performed follow-up, designed study and wrote manuscript; EDA performed follow-up, designed study, and wrote manuscript; TMM designed study, provided statistical analysis and edited manuscript; WN designed study and edited manuscript; KML performed MRI studies and image analysis, and edited manuscript; CAH enabled image acquisition and analysis, and edited manuscript; DWK designed study and edited manuscript; WGH designed study, performed MRI studies and image analysis, and edited manuscript.p
sec
bdy
bm
ack
sec
st
pAcknowledgementsp
st
pNorth Carolina Baptist Hospital Technology Development Fund (B-03-9798);p
p indent="1"- funded imaging examsp
pNational Institutes of Health R01HL074330;p
p indent="1"- funded image analysis and investigator timep
pThe Claude D. Pepper Older Americans Center, National Institutes of Health P30AG21332; andp
p indent="1"- funded investigator timep
pThe National Institutes of Health General Clinical Research Center M01RR07122.p
p indent="1"- funded image acquistionp
sec
ack
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