Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance.

BACKGROUND: Left ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta. METHODS: CMR was performed in 121 patients, 2-4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m-2), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance). RESULTS: At 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m2.L-1, EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6-month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular obstruction at baseline (EDV-/EF-: 37%, EDV+/EF-: 76%, EDV-/EF+: 38%, EDV+/EF+: 73%, p = 0.003). CONCLUSION: LV remodeling following reperfused MI is strongly influenced by the variable decrease in systemic vascular resistance under standard care vasodilating medication. The CMR monitoring of vascular resistance may help to tailor these medications for improving vascular resistance and consequently, LV ejection fraction. TRIAL REGISTRATION: NCT01109225 on ClinicalTrials.gov site (April, 2010).

Comprehensive monitoring of cardiac remodeling with aortic stroke volume values provided by a phase-contrast MRI sequence.

OBJECTIVES: Blood pressure (BP) and its changes with antihypertensive therapy are key parameters when monitoring left ventricular (LV) remodeling. This dual cross-sectional and longitudinal MRI study aimed to determine whether this monitoring is enhanced by aortic stroke volume (SV) values provided by a phase-contrast sequence. METHODS: The study involved 334 MRI examinations from 247 study participants who had no significant cardiac disease (18-85 years old, 40% with hypertension) and among whom 48 had a 2-4-year MRI follow-up. Left ventricular hypertrophy and concentric geometry were: respectively assessed according to LV mass indexed to body surface area (g/m) and mass/end-diastolic volume ratio (concentric remodeling index); and correlated with vascular parameters involving BP and the indexed SV (ml/m) determined in the ascending aorta with a phase-contrast sequence. RESULTS: Stroke volume was highly variable, ranging from 22 to 74 ml/m. The best cross-sectional correlates were: mean BP × SV product, reflecting cardiac work, for LV mass (r = 0.21); and mean BP/SV ratio, reflecting arterial load, for concentric geometry (r = 0.29). These two SV-derived parameters led to more than two-fold enhancements in cross-sectional predictions compared with BP parameters alone, whereas their longitudinal changes over time paralleled those of concentric geometry (P = 0.003 for mean BP/SV) and LV mass (P = 0.006 for mean BP × SV), suggesting direct links with cardiac remodeling. CONCLUSION: The determination of aortic SV with a phase-contrast sequence leads to a significant enhancement in the characterization and monitoring of cardiac remodeling.

Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET.

Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with (18)F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old. Arterial blood pressure was determined by cardiac catheterization and cardiac fibrosis was quantified after sacrifice. Blood pressure was similarly elevated in SHR and SHHF rats (respective systolic blood pressures at 10-months: 199 ± 39 vs. 205 ± 2 mmHg), but SHHF rats had higher body mass than SHR rats (at 10-months, 630 ± 36 vs. 413 ± 27 g, p < 0.05) and higher blood levels of cholesterol and of triglycerides. At 3 months, cardiac parameters did not show significant differences between groups but at 10-months, SHHF and SHR rats exhibited an enhancement in myocardial mass and fibrosis associated with a clear decline in LV-EF (SHHF: 46 ± 6 %; SHR: 47 ± 5 %) as compared with WKY (56 ± 6 %, p < 0.01 for both comparisons). Cardiac remodeling of SHHF rats was clearly observable by FDG-PET from the age of 10-months, but in a similar way to that observed for SHR rats, suggesting a predominant role of hypertension.

Features of cardiac remodeling, associated with blood pressure and fibrosis biomarkers, are frequent in subjects with abdominal obesity.

Incidence and prevalence of abdominal obesity (AO) are growing exponentially. Subjects with AO are at higher risk of developing heart failure. The purpose of the study was to investigate early changes in cardiac and arterial structure and function and extracellular matrix biomarkers in normotensive healthy subjects with AO. Subjects with AO and age- and sex-matched controls underwent echocardiography, MRI (cardiac remodeling index), carotid intima-media thickness, pulse wave velocity, and blood fibrosis biomarkers measurements. We enrolled 87 subjects with AO and 53 controls. Although normotensive, subjects with AO had higher systolic blood pressure (BP; 122±11 versus 116±11 mm Hg; P=0.003), left ventricular mass (94±24 versus 84±21 g; P=0.034), and cardiac remodeling index (0.67±0.16 versus 0.60±0.10 g/mL; P=0.026) but unchanged carotid intima-media thickness and pulse wave velocity. Diastolic dysfunction (E' <10 cm/s) could be detected in 38% of subjects with AO (4% in controls). Left ventricular remodeling, as assessed by cardiac remodeling index, was positively and independently associated with higher BP (systolic BP and mean arterial pressure but not diastolic BP) and AO. Higher BP, AO, and procollagen-III-N-terminal peptide (≥2.4 ng/mL) concentrations (odds ratio, 4.15 [1.42-12.2]; P=0.01) were positively associated with diastolic dysfunction. Early cardiac structural remodeling, fibrosis, and diastolic dysfunction were detectable in healthy subjects with AO. Higher BP, procollagen-III-N-terminal peptide, and AO were independently associated with early cardiac structural and functional changes. It is to be investigated whether in subjects with AO, an early BP reduction, even if normotensive, combined with weight loss may avoid adverse cardiac remodeling and protect against progression to heart failure.

Comprehensive MRI analysis of early cardiac and vascular remodeling in middle-aged patients with abdominal obesity.

OBJECTIVES: To determine, using a comprehensive MRI investigation, prevalence and vascular correlates of early left-ventricular concentric remodeling in middle-aged patients with abdominal obesity. Left-ventricular and vascular remodeling are commonly associated with hypertension, but little is known for abdominal obesity patients, a population with definite increase in cardiovascular risk and high rates of further developments of hypertension and of the metabolic syndrome. METHODS: Seventy middle-aged abdominal obesity patients (56 ±â€Š5 years, 49% women, 69% with body mass index > 30 kg/m), who had no additional cardiovascular risk factor except for untreated stage 1 hypertension (16%), and 40 controls underwent MRI for detecting concentric remodeling (increase in left-ventricular mass/end-diastolic volume ratio) and identifying potential determinants, including arterial compliance indexes [aortic pulse wave velocity and total arterial compliance (TAC)] and total peripheral vascular resistances (TPVRs). RESULTS: Twenty abdominal obesity patients (29%) had concentric remodeling (concentric remodeling+), whereas 50 did not (concentric remodeling-). Concentric remodeling+ patients were mostly men (85%), they frequently had stage 1 hypertension (45%) and few had left-ventricular hypertrophy (20%). When adjusted for sex, there was a step-by-step decline in TAC between controls (mean ±â€ŠSEM: 2.10 ±â€Š0.06 ml/mmHg), concentric remodeling- (1.82 ±â€Š0.06 ml/mmHg) and concentric remodeling+ (1.42 ±â€Š0.09 ml/mmHg, P < 0.005 for inter-group comparisons) and TPVRs were lower than controls for concentric remodeling- (14.7 ±â€Š0.5 vs. 16.8 ±â€Š0.5 ml/mmHg, P = 0.005) but not for concentric remodeling+ (17.5 ±â€Š0.7 mmHg/min per l). CONCLUSIONS: Concentric remodeling is frequently documented by MRI in the middle-aged men with abdominal obesity and in association with a decrease in TAC no longer counter-balanced by a decrease in TPVR, suggesting a remodeling from proximal to peripheral vasculature.

Localization of temporal epilepsy foci by subtraction ictal perfusion single photon emission computed tomography is enhanced when using 3D-OSEM iterative reconstruction.

OBJECTIVES: Subtraction ictal single photon emission computed tomography (SPECT) images, provided by filtered back-projection (FBP), may exhibit a confusing high level of noise. This study was aimed at assessing an optimized three-dimensional ordered subset expectation maximization (3D-OSEM) iterative reconstruction in this setting. METHODS: On phantom images, parameters of 3D-OSEM reconstruction were selected as those providing the higher signal/noise ratio but a high enough spatial resolution, equivalent to that of conventional FBP reconstruction (full width at half-maximum = 11 mm). Thereafter, subtraction ictal ethylene cysteine dimer-SPECT coregistered to MRI and reconstructed with either FBP or 3D-OSEM were compared in 21 patients with well-characterized temporal epilepsy foci (subsequent successful surgical treatment). RESULTS: On subtraction images, the use of the selected 3D-OSEM reconstruction (five iterations, 16 subsets and a 9 mm Gauss filter) instead of FBP was associated with: (i) marked reductions in background activity (0.05 ± 0.09 vs. 0.25 ± 0.18 cps, P < 0.001) and in the size of temporal foci (10 ± 7 vs. 14 ± 11 cm, P = 0.01) and (ii) a trend toward higher accuracy in identifying the involved temporal lobes (86 vs. 76%). CONCLUSION: Localization of temporal epilepsy foci by subtraction ictal SPECT is likely to be enhanced by using 3D-OSEM rather than FBP reconstruction because of marked reductions in background activity and in the size of detected foci.

Nitrate-enhanced gated SPECT in patients with primary angioplasty for acute myocardial infarction: evidence of a reversible and nitrate-sensitive impairment of myocardial perfusion.

PURPOSE: Reperfusion of myocardial infarction (MI) leads to a reversible dysfunction of coronary vessels. We hypothesised that vasodilating drugs such as nitrates might improve sestamibi uptake within viable areas of recently reperfused MI, thereby enhancing prediction of subsequent improvements in perfusion and contractility. This study was aimed at assessing nitrate-enhanced sestamibi gated SPECT after MI reperfusion. METHODS: Twenty-nine patients underwent rest followed by nitrate sestamibi gated SPECT at 9 +/- 3 days after primary angioplasty for acute MI and at follow-up, 4-10 months later. Four MBq/kg of (99m)Tc-sestamibi was injected at rest, and 12 MBq/kg after nitroglycerin spray. RESULTS: Follow-up improvements were documented for both perfusion (P+) and contractility (C+) in 18% of the 180 initially abnormal segments, in neither perfusion (P-) nor contractility (C-) in 44%, in contractility only (C+P-) in 16% and in perfusion only (C-P+) in 22%. Perfusion improvement was related to lower sestamibi uptake on baseline rest SPECT (P+: 42 +/- 15% vs P-: 50 +/- 15%, p = 0.001) and, moreover, to a higher increase between rest and nitrate uptake (P+: +9.5 +/- 6.5% vs P-: +2.0 +/- 5.9%, p < 0.001). Contractility improvement was related to sestamibi uptake on baseline nitrate SPECT (C+: 58 +/- 15% vs C-: 38 +/- 16%, p < 0.001), a variable enhancing the prediction provided by sestamibi uptake at rest (p < 0.05). CONCLUSION: The improvement in perfusion which is documented in the months following MI reperfusion is predicted by initial nitrate enhancement of sestamibi uptake, suggesting a mechanism of reversible vascular injury. In this particular setting, sestamibi uptake is a better predictor of contractility recovery when determined after nitrate administration rather than under conventional resting conditions.

Detection of myocarditis by contrast-enhanced MRI in patients presenting with acute coronary syndrome but no coronary stenosis.

PURPOSE: To prospectively assess the use of cardiac MRI with delayed contrast enhancement (DCE) for identifying patients with active myocarditis among those presenting with acute coronary syndrome (ACS) but no coronary stenosis. MATERIALS AND METHODS: A total of 27 consecutive patients (age = 45 +/- 17 years; 14 male) presenting with ACS (chest pain, positive troponin-I) and no coronary stenosis, underwent cardiac MRI 9 +/- 7 days after pain onset and 8 +/- 5 months later (N = 19). Steady-state free-precession pulse (SSFP) sequence was applied for the assessment of myocardial function and both inversion-recovery (IR) and SSFP sequences were used for analyzing the topography and extent of DCE areas. Rest sestamibi-gated-single photon emission CT (SPECT) was also systematically performed. RESULTS: Subepicardial DCE pattern typical of acute myocarditis was documented in 12 patients (44%). Ischemic DCE pattern (transmural or subendocardial focal DCE) was documented in 12 of the 15 remaining patients (44%). Patients with subepicardial DCE had: higher C-reactive protein (CRP) levels (38 +/- 32 vs. 14 +/- 24 mg/mL; P = 0.04), lower Framingham cardiovascular risk (3 +/- 3% vs. 9 +/- 5%; P < 0.001), lower incidence of perfusion SPECT defects (17% vs. 73%; P = 0.01), higher left ventricular (LV) end-diastolic volume (77 +/- 16 vs. 64 +/- 10 mL/m(2); P = 0.02), and higher regression of DCE areas at follow-up (-65 +/- 17% vs. -18 +/- 23%; P = 0.002). CONCLUSION: DCE pattern of active myocarditis can be seen in patients presenting with ACS but no coronary stenosis.

Residual stress ischaemia is associated with blood markers of myocardial structural remodelling.

BACKGROUND: Long-term prognosis of coronary artery disease (CAD) patients is worsened when stress ischemia persists on treatment, but the relationship with adverse cardiac remodelling had never been investigated. AIM: To analyze changes in blood markers of fibrosis in patients with chronic CAD exhibiting exercise ischaemia. METHODS: Circulating markers of collagen: (i) turnover (amino-terminal propeptide of collagen-III [PIIINP]) and (ii) degradation (matrix metalloproteinase 1 [MMP-1]), were obtained in 139 CAD patients referred for exercise 201Tl-SPECT. RESULTS: In the 57 patients who had SPECT-ischaemia, PIIINP was higher (4.3+/-2.9 microg L-1 vs. 3.1+/-1.5 microg L-1, p=0.002) and MMP-1 lower (3.8+/-2.1 microg L-1 vs. 4.7+/-2.8 microg L-1, p=0.04) than in the 82 patients without SPECT-ischaemia. PIIINP was independently related to LV volume, SPECT-ischaemia and age, whereas MMP-1 was related to current treatment with ACEI and beta-blockers (p<0.05). In the 104 patients with a normal LV ejection fraction, only PIIINP was related to SPECT-ischaemia (4.1+/-2.2 microg L-1 vs. 3.1+/-1.5 microg L-1, p=0.01). CONCLUSION: In patients with chronic CAD, exercise ischaemia is associated with increased collagen-III turnover, independently of concomitant medications and even when LV ejection fraction is normal. Long-term, this increase might relate to adverse cardiac remodelling even when cardiac function is not clearly affected at baseline.

Initial infarct size predicts subsequent cardiac remodeling in the rat infarct model: an in vivo serial pinhole gated SPECT study.

UNLABELLED: The rat infarct model is widely used to study left ventricular (LV) remodeling, a main cause of heart failure characterized by progressive LV dilatation. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The aim of this study was to assess this new imaging technique for predicting and quantifying variable LV remodeling from the rat infarct model. METHODS: Pinhole 99mTc-sestamibi gated SPECT was validated for determining LV volume and identifying the necrotic and nonviable LV segments (<50% of 99mTc-sestamibi uptake) in rats, and it was applied to monitor rat LV function from 48 h to 12 wk after occlusion of the left anterior descending coronary artery (LAD) (n = 20) or sham operation (n = 9). RESULTS: In LAD-occluded rats, 48-h SPECT necrosis was large (> or =30% LV) in 6, limited (<30% LV) in 6, and undetectable in 8. End-diastolic volume of LAD-occluded rats was equivalent to that of sham-operated rats at 48 h (320 +/- 84 microL vs. 293 +/- 48 microL; not significant) but became higher at 12 wk (501 +/- 191 microL vs. 343 +/- 46 microL; P = 0.01). The follow-up increase in end-diastolic volume, which reflects the remodeling process, was closely related to the initial extent of necrosis revealed by the SPECT images (P < 0.001; R2= 0.85). This increase was limited in sham-operated rats (50 +/- 15 microL) and in the LAD-occluded rats with undetectable necrosis (55 +/- 35 microL) but it was around 3- and 7-fold higher in the LAD-occluded rats with limited (165 +/- 57 microL) and large (366 +/- 113 microL) necrosis, respectively. CONCLUSION: The variable LV remodeling documented after coronary occlusion in rats closely relates to the variable extent of necrosis provided by this model. Pinhole gated SPECT allows this remodeling to be predicted and quantified and, hence, constitutes an original tool for the experiments scheduled on the rat infarct model.

Gated SPECT assessment of left ventricular function is sensitive to small patient motions and to low rates of triggering errors: a comparison with equilibrium radionuclide angiography.

BACKGROUND: Patient displacements and errors in R-wave detection are the main causes of inaccurate acquisition for gated single photon emission computed tomography (SPECT) and equilibrium radionuclide angiography (RNA). This study aimed to compare the influences of both factors between gated SPECT and RNA determinations of left ventricular ejection fraction. METHODS AND RESULTS: On gated SPECT and RNA acquisitions, recorded in 20 patients with coronary artery disease, we simulated the consequences of (1) 3-dimensional patient displacements of low (6.7 mm), moderate (13.4 mm), and high amplitude (20.1 mm) and (2) an erroneous triggering on T waves in 10% to 40% of recorded beats. Absolute values of left ventricular ejection fraction changes from baseline were higher with gated SPECT compared with RNA for patient displacements of low amplitude (5.0% +/- 3.8% vs 1.2% +/- 0.9%, P < .001) or moderate amplitude (10.0% +/- 6.2% vs 3.0% +/- 2.3%, P = .001) but not for patient displacements of high amplitude (12% +/- 9% vs 9% +/- 7%, P = not significant) and inaccurate triggering (for 20% T-wave triggering, 8.9% +/- 3.6% vs 7.9% +/- 3.0%; P = not significant). CONCLUSION: Contrary to RNA, gated SPECT is vulnerable to small patient displacements, and thus, specific efforts might be useful for limiting this potential cause of erroneous results. Both techniques may be affected by low rates of triggering errors, suggesting that small acceptance windows on cycle length should be recommended not only for RNA but also for gated SPECT.

Residual exercise SPECT ischemia on treatment is a main determinant of outcome in patients with coronary artery disease treated medically at long-term with beta-blockers.

BACKGROUND: Beta-blockers are potent anti-ischemic medications, able to improve prognosis in patients with coronary artery disease (CAD). However, it is not known whether beta-blockers have the same beneficial prognostic effect when residual ischemia persists on treatment. METHODS AND RESULTS: The prognostic impact of exercise single photon emission computed tomography (SPECT) ischemia was analyzed in 442 patients with chronic CAD, who were treated with beta-blockers and who were referred to exercise thallium 201 SPECT, while they were receiving their daily-life medications. Ischemic and viable myocardium was documented on Tl-201 SPECT in 190 patients (43%), of whom only 23% had angina and only 26% had positive exercise testing results. During a follow-up of 3.8 +/- 1.7 years, 36 patients died and survival curves were progressively divergent between patients with and those without ischemic and viable myocardium: at 5 years, the respective survival rates were 81% +/- 4% and 94% +/- 2% (P =.004). By multivariate analysis, the best independent predictors of death were large extent of necrosis (>25% of left ventricle on Tl-201 SPECT, P <.001) and ischemic and viable myocardium (P =.001). CONCLUSIONS: In the CAD patients treated on a long-term basis with beta-blockers, survival is strongly influenced by persistent exercise SPECT ischemia on treatment. Therefore exercise SPECT on treatment could be a useful tool for selecting those who might benefit from additional anti-ischemic therapeutic interventions.