Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Impact of alcohol septal ablation on left anterior descending coronary artery blood flow in hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The aim of this study was to evaluate the effects of alcohol septal ablation (ASA) on coronary blood flow in symptomatic hypertrophic obstructive cardiomyopathy (HOCM) using cardiac MR (CMR) coronary flow measurements. Background CMR flow mapping enables quantification of coronary blood flow in a noninvasive way. Both left ventricular outflow tract (LVOT) gradient reduction and myocardial scarring after ASA are expected to influence left anterior descending (LAD) coronary blood flow. METHODS: Cine, contrast-enhanced (CE) imaging and breath-hold CMR phase contrast velocity mapping were performed at baseline and 1 and 6 months after ASA in seven patients. Changes of coronary blood flow were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LVOT gradient reduction, and LV rate pressure product (LVRPP). RESULTS: A significant mass reduction was observed both in the target septal myocardium and in the total myocardium (both P < 0.01). Mean myocardial infarct size was 23 +/- 12 g (range 7.3-41.6 g). LVRPP decreased from 13,268 +/- 2,212 to 10,685 +/- 3,918 at 1 month (P = 0.05) and 9,483 +/- 2,496 mmHg beats/min at 6 months' follow-up (P < 0.01). LAD coronary blood flow decreased from 100 +/- 37 ml/min at baseline to 84 +/- 54 ml/min (P = 0.09) at 1 month and 67 +/- 33 ml/min at 6 months follow-up (P < 0.01). A significant correlation was found between the change in LVRPP and LAD coronary flow at 1 month follow-up (r = 0.83, P = 0.02). CE-infarct size tended to modulate the blood flow changes over time (P = 0.12); no correlation was observed between enzyme release, volume of ethanol or both septal and total mass reduction and coronary blood flow. CONCLUSION: The reduction in coronary blood flow is primarily associated with diminished LV loading conditions, whereas the induction of metabolically inactive myocardial scar tissue by ASA did not significantly influence the changes in coronary blood flow.

Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy.

Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 +/- 0.97 vs. 2.93 +/- 0.64 ml min(-1) g(-1), P < 0.05). In contrast to controls (1.38 +/- 0.15 to 1.25 +/- 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 +/- 0.11 to 0.88 +/- 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients.

Functional outcome after revascularization in patients with chronic ischemic heart disease: a quantitative late gadolinium enhancement CMR study evaluating transmural scar extent, wall thickness and periprocedural necrosis.

In patients with chronic ischemic myocardial dysfunction, late gadolinium enhancement CMR (LGE-CMR) accurately depicts the regional extent of fibrosis and predicts functional recovery after revascularization. We hypothesized that the predictive accuracy of LGE-CMR could be optimized by not only taking into account the transmural extent of hyperenhancement but also the amount of residual, non-enhanced viable myocardium, and procedure related necrosis. We studied 45 patients with chronic ischemic left ventricular dysfunction, who underwent cine and LGE-CMR 1 month before and 3 months after surgical or percutaneous revascularization. Segmental and global function, scar, presence of a significant residual viable rim (defined as >or=4.5 mm), and procedure related necrosis were fully quantified using standardized methods and objective thresholds. Sixty percent of segments without hyperenhancement showed functional improvement at follow-up. No improvement was observed in segments with >75% segmental extent of hyperenhancement (SEH), while segments with 1-25%, 26-50%, and 51-75% SEH were 4, 8, and 20 times less likely to improve (multilevel analysis, p<0.001). Thickness of the viable rim largely paralleled total wall thickness; therefore, the presence of a significant viable rim did not provide additional diagnostic value beyond SEH. Procedure related necrosis was found in 12 (27%) patients. The presence of procedure related necrosis was the only (negative) predictor of changes in left ventricular volumes and ejection fraction. In conclusion, we found that functional outcome after revascularization was influenced by both transmural extent of hyperenhancement and procedure related necrosis. However, the presence of a significant residual, viable rim was of no additional diagnostic value.

Extent of myocardial infarction and reverse remodeling assessed by cardiac magnetic resonance in patients with and without right bundle branch block following alcohol septal ablation for obstructive hypertrophic cardiomyopathy.

Percutaneous alcohol septal ablation (ASA) is an established technique for the relief of refractory symptoms in patients with obstructive hypertrophic cardiomyopathy. Most subjects develop right bundle branch block (RBBB) after ASA, but it is not known whether these patients have similar infarct characteristics, which may influence left ventricular (LV) pressure gradient reduction and reverse remodeling, compared with those without RBBB. Twenty-seven consecutive patients (15 men, 12 women; mean age 62 +/- 16 years) were studied with electrocardiography and cardiac magnetic resonance imaging at baseline and 1 and 6 months (n = 25) after ASA. Infarct size and location were determined at 1 month by delayed contrast-enhanced cardiac magnetic resonance imaging. The 17 subjects who developed RBBB tended to have larger infarcts (creatine kinase-MB 251 +/- 92 vs 148 +/- 97 IU, p = 0.03; cardiac magnetic resonance imaging mass 22.5 +/- 9.3 vs 16.6 +/- 8.3 g, p = 0.1) and were more likely to have sustained anterior and inferior septal transmural infarctions (9 of 17 vs 1 of 10, p = 0.03) than those without RBBB. Those who developed RBBB had greater LV mass reductions at 6 months (46 +/- 26 vs 29 +/- 13 g, p = 0.04) despite similar reductions in LV pressure gradients (64 +/- 31 vs 56 +/- 32 mm Hg). In conclusion, patients who develop RBBB after ASA tend to have more extensive transmural septal infarctions and greater reverse remodeling than those without RBBB.

Septal ablation in hypertrophic obstructive cardiomyopathy improves systolic myocardial function in the lateral (free) wall: a follow-up study using CMR tissue tagging and 3D strain analysis.

AIMS: Alcohol septal ablation (ASA) has been successful in the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study is to evaluate the effects of ethanol-induced myocardial infarcts on regional myocardial function using cardiac magnetic resonance (CMR) tissue tagging and 3-dimensional (3D) strain analysis. METHODS AND RESULTS: In nine patients (age 52+/-15 years) who underwent ASA, CMR was performed prior to and 6 months after the procedure. Regional myocardial mass was evaluated using cine imaging. Myocardial tagging was used to calculate systolic 3D myocardial strain values. These strain values were used to calculate the shortening index (SI), a robust parameter for myocardial contraction. Maximum end-systolic (ES) SI and systolic SI rate were quantified in three circumferential segments: septum, adjacent, and remote (lateral) myocardium. Compared with baseline, septal and non-septal mass decreased at follow-up (from 72+/-27 to 59+/-21 g; P=0.008 and from 131+/-34 to 109+/-30 g; P=0.008, respectively). In the septum, maximum ES SI and SI rate remained unchanged after ASA. In adjacent myocardium, ES SI remained unchanged, whereas SI rate improved (from -56.5+/-21.1 to -70.0+/-16.7%/s; P=0.02). Both ES SI and SI rate improved significantly in remote myocardium (from -16.9+/-2.8 to -18.8+/-3.2%; P=0.02 and from -70.3+/-9.2 to -86.1+/-15.0%/s; P=0.01, respectively). CONCLUSION: Reduction of left ventricular (LV) outflow tract obstruction in symptomatic HOCM is associated with a significant reduction in myocardial mass and improvement of intramural systolic function in the lateral (remote) wall, indicating reversed LV remodelling.

Regional heterogeneity of resting perfusion in hypertrophic cardiomyopathy is related to delayed contrast enhancement but not to systolic function: a PET and MRI study.

BACKGROUND: Regional differences in resting myocardial blood flow (MBF) have been observed in patients with hypertrophic cardiomyopathy (HCM), but their determinants are currently unknown. This study verifies whether MBF at rest in HCM is related to delayed contrast enhancement (DCE) or regional systolic function (or both) as determined by magnetic resonance imaging. METHODS AND RESULTS: Fourteen patients with HCM were studied. MBF was measured with positron emission tomography by use of oxygen 15-labeled water. DCE and tissue tagging, to calculate end-systolic circumferential shortening (Ecc), were obtained with magnetic resonance imaging. The mean resting MBF was 0.78 +/- 0.19 mL x min(-1) x mL(-1), and there was a trend toward reduced MBF in the septum (0.72 +/- 0.11 mL x min(-1) x mL(-1)) compared with that in the lateral wall (0.84 +/- 0.29 mL x min(-1) x mL(-1)) (P = .092). The distribution patterns of DCE and Ecc were both heterogeneous, displaying significantly increased enhancement and impaired regional systolic function in the hypertrophic septum compared with the lateral wall (both P < .001). Resting MBF was inversely related to the extent of DCE (r = -0.30, P < .001), whereas MBF was not significantly related to Ecc (r = -0.15, P = .072). CONCLUSIONS: Regional heterogeneity of resting perfusion in HCM is related to the extent of DCE but not to regional systolic function.

Measurement of left ventricular volumes and function with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic resonance imaging.

BACKGROUND: Positron emission tomography (PET) with inhaled oxygen 15-labeled carbon monoxide (CO) is used as a marker of myocardial blood pool. Only a limited number of studies with small numbers of patients have reported on the assessment of left ventricular (LV) volumes by use of O-15-labeled CO. The aim of this study was to compare LV volumes and function as measured by routinely acquired blood pool images by use of gated O-15-labeled CO PET with the reference technique, cardiovascular magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty-four subjects with a varying degree of LV function were studied. LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were determined by both MRI and gated PET by use of O-15-labeled CO. Volumes were comparable with respect to LVEDV (196 +/- 83 and 192 +/- 91 mL, respectively; P = not significant). LVESV, however, was slightly overestimated by PET (119 +/- 85 and 136 +/- 94 mL, respectively; P < .05), resulting in a significant underestimation of LVEF (44% +/- 19% and 35% +/- 18%, respectively; P < .05). Observed correlations for LVEDV, LVESV, and LVEF were 0.90, 0.96, and 0.86, respectively (all P < .01). CONCLUSIONS: Gated O-15-labeled CO PET measurements of LVEDV, LVESV, and LVEF show good correlation with MRI over a wide range of LV volumes during routinely acquired blood pool images. LVEF, however, may be underestimated compared with MRI.

Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET.

UNLABELLED: Delayed contrast enhancement (DCE) visualized by cardiac MRI (CMR) is a common feature in patients with hypertrophic cardiomyopathy (HCM), presumed to be related to myocardial fibrosis. The pathophysiologic basis of hyperenhancement in this patient group, however, remains unclear as limited histologic comparisons are available. The present study compares the perfusable tissue index (PTI), an alternative marker of myocardial fibrosis obtained by PET, with DCE-CMR in HCM. METHODS: Twenty-one patients with asymmetric septal HCM, 12 chronic myocardial infarction (MI) patients, and 6 age-matched healthy control subjects were studied with DCE-CMR and PET. PET was performed using (15)O-labeled water and carbon monoxide to obtain the PTI. RESULTS: No hyperenhancement was observed in control subjects and the PTI was within normal limits (1.10 +/- 0.07 [mean +/- SD]). In MI patients, the extent of hyperenhancement (25% +/- 16% [mean +/- SD]) was inversely related to the decrease in the PTI (0.94 +/- 0.12; r = -0.65, P < 0.05). Average hyperenhancement in HCM was 14% +/- 12%, predominantly located in the interventricular septum. The PTI in the hypertrophied interventricular septum, however, was not reduced (1.12 +/- 0.13). Furthermore, in contrast to MI patients, there was a modest positive correlation between the extent of DCE and the PTI in HCM (r = 0.45, P < 0.05). CONCLUSION: DCE in the hypertrophied septum of HCM patients is not accompanied by a decline in the PTI, and there is a positive correlation between the extent of DCE and the PTI. These results suggest that hyperenhancement may not be caused solely by fibrotic replacement scarring in this patient group. Other pathologic changes associated with HCM may also cause gadolinium-diethylenetriaminepentaacetic acid hyperenhancement.

Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR.

PURPOSE: To evaluate a standardized definition of delayed hyperenhancement in the analysis of contrast-enhanced cardiac magnetic resonance (ceCMR) imaging. PATIENTS AND METHODS: CeCMR was performed in 15 patients with chronic ischemic heart disease. Delayed hyperenhancement was analyzed both by visual analysis by an experienced team of observers, and after thresholding the window setting of the images at 2, 3, 4, 5, and 6 SD above the mean signal intensity of remote, normal myocardium in the same slice. In each patient, total infarct size (TIS) and segmental infarct extent (SIE) were calculated. RESULTS: TIS and SIE were 22.9 +/- 12.2 mL and 32 +/- 28% after visual analysis. Thresholding the window setting at 2, 3, 4, and 6 SD above signal intensity of remote caused a 40%, 31%, and 17% increase (p < 0.007) and a 7% decrease (p = NS) in TIS, and a 75%, 41%, and 16% increase and 22% decrease in SIE (p < 0.001), respectively. There was no difference between visual analysis and analysis after thresholding at 5 SD. CONCLUSION: Analyzing ceCMR with a standardized definition of hyperenhancement related to the signal of remote, nonenhanced myocardium may result in considerable overestimation of infarct size at the usual cut-off of 2 SD.

Early onset and progression of left ventricular remodeling after alcohol septal ablation in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM), which leads to left ventricular remodeling. We sought to describe the early to midterm changes and modulating factors of the remodeling process using cardiac MRI (CMR). METHODS AND RESULTS: CMR was performed at baseline and 1 and 6 months after ASA in 29 patients with HOCM (age 52+/-16 years). Contrast-enhanced CMR showed no infarct-related hyperenhancement outside the target septal area. Septal mass decreased from 75+/-23 g at baseline to 68+/-22 and 58+/-19 g (P<0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass decreased from 141+/-41 to 132+/-40 and 111+/-27 g (P<0.001), respectively. Analysis of temporal trends revealed that septal mass reduction was positively associated with contrast-enhanced infarct size and transmural or left-sided septal infarct location at both 1 and 6 months. Remote mass reduction was associated with infarct location at 6 months but not with contrast-enhanced infarct size. By linear regression analysis, percentage remote mass reduction correlated significantly with LVOT gradient reduction at 6-month follow-up (P=0.03). CONCLUSIONS: Left ventricular remodeling after ASA occurs early and progresses on midterm follow-up, modulated by CMR infarct size and location. Remote mass reduction is associated with infarct location and correlates with reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is, at least in part, afterload dependent and reversible and is not exclusively caused by the genetic disorder.

Myocardial infarction after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: evaluation by contrast-enhanced magnetic resonance imaging.

OBJECTIVES: The aim of this study was to evaluate myocardial infarction induced by percutaneous transluminal septal myocardial ablation (PTSMA) in symptomatic patients with hypertrophic obstructive cardiomyopathy using contrast-enhanced (CE) magnetic resonance imaging (MRI). BACKGROUND: Contrast-enhanced MRI delineates the extent of myocardial infarction in coronary artery disease, but its role in ethanol-induced infarction has not been established. METHODS: Cine and CE MRI were performed before and one month after PTSMA in 24 patients. Size and location of the induced infarction were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LV outflow tract gradient reduction, and coronary ablation site. RESULTS: One month after PTSMA, regional hyperenhancement was visualized in the basal interventricular septum in all patients. Mean infarction size was 20 +/- 9 g, corresponding to 10 +/- 5% and 31 +/- 16% of total LV and septal mass, respectively. Total LV mass decreased from 219 +/- 64 to 205 +/- 64 g (p < 0.01), and septal mass from 76 +/- 25 to 68 +/- 22 g (p < 0.01). Total LV mass reduction exceeded septal mass reduction (p < 0.01). Infarction size correlated with peak creatine phosphokinase-MB (beta = 0.67, p < 0.01), volume of ethanol administered (beta = 0.47, p = 0.02), total LV and septal mass reduction (beta = 0.50, p = 0.02; beta = 0.73, p < 0.01), and gradient reduction (beta = 0.63, p < 0.01). Seven patients with exclusively right-sided septal infarction had smaller infarction size and less gradient reduction than remaining patients with left-sided or transmural infarction (p < 0.01). In five of these, PTSMA was performed distal in the target artery. CONCLUSIONS: Contrast-enhanced MRI allowed detailed evaluation of size and location of septal myocardial infarction induced by PTSMA. Infarction size correlated well with clinical indexes of infarct size.

Delayed contrast-enhanced magnetic resonance imaging for the prediction of regional functional improvement after acute myocardial infarction.

OBJECTIVES: We evaluated whether delayed contrast-enhanced magnetic resonance imaging (DCE-MRI) using an extracellular contrast agent could predict improvement of dysfunctional but viable myocardium after acute reperfused myocardial infarction (MI). BACKGROUND: The transmural extent of hyperenhancement at DCE-MRI has been related to improvement of function in reperfused MI. However, evidence is still limited, and earlier reports have produced conflicting results regarding the significance of contrast patterns after infarction. METHODS: Thirty patients (mean age 59 +/- 11 years, 27 males) underwent cine MRI and DCE-MRI 7 +/- 3 days after a first reperfused acute MI and follow-up cine MRI at 13 +/- 3 weeks. Segmental wall thickening and segmental extent of hyperenhancement were scored in 1,689 segments. RESULTS: Of 500 dysfunctional segments, 273 (55%) improved at follow-up. There was no difference in likelihood of improvement or complete functional recovery between segments with 0% and 1% to 25% hyperenhancement. The likelihood of improvement of segments without hyperenhancement was 2.9, 14.3, and 20 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). The likelihood of complete functional recovery of segments without hyperenhancement was 3.8, 11.1, and 50 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). CONCLUSIONS: In patients with recent reperfused MI, functional improvement of stunned myocardium is predicted by DCE-MRI.

Variable clinical manifestation of a novel missense mutation in the alpha-tropomyosin (TPM1) gene in familial hypertrophic cardiomyopathy.

OBJECTIVES: This study was initiated to identify the disease-causing genetic defect in a family with hypertrophic cardiomyopathy (HCM) and high incidence of sudden death. BACKGROUND: Familial hypertropic cardiomyopathy (FHC) is an autosomal dominant transmitted disorder that is genetically and clinically heterogeneous. Mutations in 11 genes have been associated with the pathogenesis of the disease. METHODS: We studied a large FHC family, first by linkage analysis, to identify the gene involved, and subsequently screened the gene, encoding alpha-tropomyosin (TPM1), for mutations by using single-strand conformation polymorphism and sequencing analysis. RESULTS: Twelve family members presented clinical features of HCM, five of whom died at young age, while others had only mild clinical features. Marker analysis showed linkage for the TPM1 gene on chromosome 15q22 (maximal logarithm of the odds score is 5.16, theta = 0); subsequently, a novel missense mutation (Glu62Gln) was identified. CONCLUSIONS: The novel mutation identified in TPM1 is associated with the clinical features of cardiac hypertrophy in all but one genetically affected member of this large family. The clinical data suggest a malignant phenotype at young age with a variable clinical manifestation and penetrance at older age. The Glu62Gln mutation is the sixth TPM1 mutation identified as the cause of FHC, indicating that mutations in this gene are very rare. This is the first reported amino acid substitution at the f-position within the coiled-coil structure of the tropomyosin protein.