Hemodynamic Insights into Combined Fractional Flow Reserve and Instantaneous Wave-Free Ratio Assessment Through Quantitative [15O]H2O PET Myocardial Perfusion Imaging.

In patients evaluated for obstructive coronary artery disease (CAD), guidelines recommend using either fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. This study compared [15O]H2O PET-derived absolute myocardial perfusion between vessels with concordant and discordant FFR and iFR measurements. Methods: We included 197 patients suspected of obstructive CAD who had undergone [15O]H2O PET perfusion imaging and combined FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF, and coronary flow reserve (CFR) were compared among 4 groups: FFR low/iFR low (n = 79), FFR high/iFR low (n = 22), FFR low/iFR high (n = 22), and FFR high/iFR high (n = 345). Predefined [15O]H2O PET thresholds for ischemia were 2.3 mL·min-1·g-1 or less for hyperemic MBF and 2.5 or less for CFR. Results: Hyperemic MBF was lower in the concordant low (2.09 ± 0.67 mL·min-1·g-1), FFR high/iFR low (2.41 ± 0.80 mL·min-1·g-1), and FFR low/iFR high (2.40 ± 0.69 mL·min-1·g-1) groups compared with the concordant high group (2.91 ± 0.84 mL·min-1·g-1) (P < 0.001, P = 0.004, and P < 0.001, respectively). A lower CFR was observed in the concordant low (2.37 ± 0.76) and FFR high/iFR low (2.64 ± 0.84) groups compared with the concordant high group (3.35 ± 1.07, P < 0.01 for both). However, for vessels with either low FFR or low iFR, quantitative hyperemic MBF and CFR values exceeded the ischemic threshold in 38% and 49%, respectively. In addition, resting MBF exhibited a negative correlation with iFR (P < 0.001) and was associated with FFR low/iFR high discordance compared with concordant low FFR/low iFR measurements, independent of clinical and angiographic characteristics, as well as hyperemic MBF (odds ratio [OR], 0.41; 95% CI, 0.26-0.65; P < 0.001). Conclusion: We found reduced myocardial perfusion in vessels with concordant low and discordant FFR/iFR measurements. However, FFR/iFR combinations often inaccurately classified vessels as either ischemic or nonischemic when compared with hyperemic MBF and CFR. Furthermore, a lower resting MBF was associated with a higher iFR and the occurrence of FFR low/iFR high discordance. Our study showed that although combined FFR/iFR assessment can be useful to estimate the hemodynamic significance of coronary lesions, these pressure-derived indices provide a limited approximation of [15O]H2O PET-derived quantitative myocardial perfusion as the physiologic standard of CAD severity.

The relevance of a multidomain geriatric assessment in older patients with heart failure.

AIMS: Physical frailty screening is more commonly performed at outpatient heart failure (HF) clinics. However, this does not incorporate other common geriatric domains. This study assesses whether a multidomain geriatric assessment, in comparison with HF severity or physical frailty, is associated with short-term adverse outcomes. METHODS AND RESULTS: This is a prospective cohort study of 197 patients with HF (mean age 78, 44% female) attending outpatient HF clinics. HF severity was assessed with New York Heart Association class (I-II versus III-IV) and N-terminal pro b-type natriuretic peptide levels. Physical frailty was assessed with the Fried frailty criteria (not frail, pre-frail, and frail). The following geriatric domains were assessed: physical function, nutrition, polypharmacy, cognition, and dependency in activities of daily living. Logistic regression analyses adjusted for age, sex, diabetes and kidney function assessed 3 month risk of adverse health outcomes (emergency department visits, hospital admissions, and/or death) according to HF severity, physical frailty, and number of affected domains. Number (%) of patients with HF with no, 1, 2, and ≥3 domains affected were 36 (18%), 61 (31%), 58 (29%), and 42 (21%). Seventy-four adverse outcomes were experienced in 50 patients at follow-up. Severity of HF and physical frailty were not significantly associated with an increased risk of adverse health outcomes. However, increasing number of affected domains were significantly associated with an increased risk of adverse outcomes. Compared with no domains affected, odds ratios (95% confidence interval) for 1, 2, and ≥3 domains were 1.8 (0.5-6.5), 4.5 (1.3-15.4), and 7.2 (2.0-26.3) (P-trend <0.01). Further adjustment for HF severity and frailty status slightly attenuated the effect estimates (P-trend 0.02). CONCLUSIONS: Having limitations in multiple domains appears more strongly associated with short-term adverse outcomes than HF severity and physical frailty. This may illustrate the potential added value of a multidomain geriatric assessment in the evaluation and treatment of patients with HF with respect to relevant short-term health outcomes.

Assessment of aortic stiffness in patients with ankylosing spondylitis using cardiovascular magnetic resonance.

To evaluate aortic stiffness in patients with ankylosing spondylitis (AS) using cardiovascular magnetic resonance (CMR) and to assess its association with AS characteristics and left ventricular (LV) remodeling. In this prospective study, 14 consecutive AS patients were each matched to two controls without cardiovascular symptoms or known cardiovascular disease who underwent CMR imaging for the assessment of aortic arch pulse wave velocity (PWV) at 1.5 Tesla. To enhance comparability of the samples, matching was done with replacement resulting in 20 unique controls. Only AS patients with abnormal findings on screening echocardiography were included in this exploratory study. Cine CMR was used to assess LV geometry and systolic function, and late gadolinium enhancement was performed to determine the presence of myocardial hyperenhancement (i.e., fibrosis). Aortic arch PWV was significantly higher in the AS group compared with the control group (median 9.7 m/s, interquartile range [IQR] 7.1 to 11.8 vs. 6.1 m/s, IQR 4.6 to 7.6 m/s; p < 0.001). PWV was positively associated with functional disability as measured by BASFI (R: 0.62; p = 0.018). Three patients (21%) with a non-ischemic pattern of hyperenhancement showed increased PWV (11.7, 12.3, and 16.5 m/s) as compared to the 11 patients without hyperenhancement (9.0 m/s, IQR 6.6 to 10.5 m/s; p = 0.022). PWV was inversely associated with LV ejection fraction (R: - 0.63; p = 0.015), but was not found to be statistically correlated to LV volumes or mass. Aortic arch PWV was increased in our cohort of patients with AS. Higher PWV in the aortic arch was associated with functional disability, the presence of non-ischemic hyperenhancement, and reduced LV systolic function.

The influence of microvascular injury on native T1 and T2* relaxation values after acute myocardial infarction: implications for non-contrast-enhanced infarct assessment.

OBJECTIVES: Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI. METHODS: Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium. RESULTS: Average T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p<0.001). CONCLUSION: The presence of MVI profoundly affects MOLLI-measured native T1 values. T2* mapping suggested that this may be the result of intramyocardial haemorrhage. These findings have important implications for the interpretation of native T1 values shortly after AMI. KEY POINTS: • Microvascular injury after acute myocardial infarction affects local T1 and T2* values. • Infarct zone T1 values are lower if microvascular injury is present. • T2* mapping suggests that low infarct T1 values are likely haemorrhage. • T1 and T2* values are complimentary for correctly assessing post-infarct myocardium.

In vivo assessment of myocardial viability after acute myocardial infarction: A head-to-head comparison of the perfusable tissue index by PET and delayed contrast-enhanced CMR.

BACKGROUND: Early recognition of viable myocardium after acute myocardial infarction (AMI) is of clinical relevance, since affected segments have the potential of functional recovery. Delayed contrast-enhanced magnetic resonance imaging (DCE-CMR) has been validated extensively for the detection of viable myocardium. An alternative parameter for detecting viability is the perfusable tissue index (PTI), derived using [15O]H2O positron emission tomography (PET), which is inversely related to the extent of myocardial scar (non-perfusable tissue). The aim of the present study was to investigate the predictive value of PTI on recovery of LV function as compared to DCE-CMR in patients with AMI, after successful percutaneous coronary intervention (PCI). METHODS: Thirty-eight patients with ST elevation myocardial infarction (STEMI) successfully treated by PCI were prospectively recruited. Subjects were examined 1 week and 3 months (mean follow-up time: 97 ± 10 days) after AMI using [15O]H2O PET and DCE-CMR to assess PTI, regional function and scar. Viability was defined as recovery of systolic wall thickening ≥3.0 mm at follow-up by use of CMR. A total of 588 segments were available for serial analysis. RESULTS: At baseline, 180 segments were dysfunctional and exhibited DCE. Seventy-three (41%) of these dysfunctional segments showed full recovery during follow-up (viable), whereas 107 (59%) segments remained dysfunctional (nonviable). Baseline PTI of viable segments was 0.94 ± 0.09 and was significantly higher compared to nonviable segments (0.80 ± 0.13, P < .001). The optimal cut-off value for PTI was ≥0.85 with a sensitivity of 85% and specificity of 72%, and an area under the curve (AUC) of 0.82. In comparison, a cut-off value of <32% for the extent of DCE resulted in a sensitivity of 72% and a specificity of 69%, and an AUC of 0.75 (AUC PTI vs DCE P = .14). CONCLUSION: Assessment of myocardial viability shortly after reperfused AMI is feasible using PET. PET-derived PTI yields a good predictive value for the recovery of LV function in PCI-treated STEMI patients, in excellent agreement with DCE-CMR.

Cost-minimization analysis of three decision strategies for cardiac revascularization: results of the "suspected CAD" cohort of the european cardiovascular magnetic resonance registry.

BACKGROUND: Coronary artery disease (CAD) continues to be one of the top public health burden. Perfusion cardiovascular magnetic resonance (CMR) is generally accepted to detect CAD, while data on its cost effectiveness are scarce. Therefore, the goal of the study was to compare the costs of a CMR-guided strategy vs two invasive strategies in a large CMR registry. METHODS: In 3'647 patients with suspected CAD of the EuroCMR-registry (59 centers/18 countries) costs were calculated for diagnostic examinations (CMR, X-ray coronary angiography (CXA) with/without FFR), revascularizations, and complications during a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive CXA and revascularization at the discretion of the treating physician (=CMR + CXA-strategy). In the hypothetical invasive arm, costs were calculated for an initial CXA and a FFR in vessels with ≥50% stenoses (=CXA + FFR-strategy) and the same proportion of revascularizations and complications were applied as in the CMR + CXA-strategy. In the CXA-only strategy, costs included those for CXA and for revascularizations of all ≥50% stenoses. To calculate the proportion of patients with ≥50% stenoses, the stenosis-FFR relationship from the literature was used. Costs of the three strategies were determined based on a third payer perspective in 4 healthcare systems. RESULTS: Revascularizations were performed in 6.2%, 4.5%, and 12.9% of all patients, patients with atypical chest pain (n = 1'786), and typical angina (n = 582), respectively; whereas complications (=all-cause death and non-fatal infarction) occurred in 1.3%, 1.1%, and 1.5%, respectively. The CMR + CXA-strategy reduced costs by 14%, 34%, 27%, and 24% in the German, UK, Swiss, and US context, respectively, when compared to the CXA + FFR-strategy; and by 59%, 52%, 61% and 71%, respectively, versus the CXA-only strategy. In patients with typical angina, cost savings by CMR + CXA vs CXA + FFR were minimal in the German (2.3%), intermediate in the US and Swiss (11.6% and 12.8%, respectively), and remained substantial in the UK (18.9%) systems. Sensitivity analyses proved the robustness of results. CONCLUSIONS: A CMR + CXA-strategy for patients with suspected CAD provides substantial cost reduction compared to a hypothetical CXA + FFR-strategy in patients with low to intermediate disease prevalence. However, in the subgroup of patients with typical angina, cost savings were only minimal to moderate.

Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations.

AIMS: Disease mechanisms regarding hypertrophic cardiomyopathy (HCM) are largely unknown and disease onset varies. Sarcomere mutations might induce energy depletion for which until now there is no direct evidence at sarcomere level in human HCM. This study investigated if mutations in genes encoding myosin-binding protein C (MYBPC3) and myosin heavy chain (MYH7) underlie changes in the energetic cost of contraction in the development of human HCM disease. METHODS AND RESULTS: Energetic cost of contraction was studied in vitro by measurements of force development and ATPase activity in cardiac muscle strips from 26 manifest HCM patients (11 MYBPC3mut, 9 MYH7mut, and 6 sarcomere mutation-negative, HCMsmn). In addition, in vivo, the ratio between external work (EW) and myocardial oxygen consumption (MVO2) to obtain myocardial external efficiency (MEE) was determined in 28 pre-hypertrophic mutation carriers (14 MYBPC3mut and 14 MYH7mut) and 14 healthy controls using [(11)C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging. Tension cost (TC), i.e. ATPase activity during force development, was higher in MYBPC3mut and MYH7mut compared with HCMsmn at saturating [Ca(2+)]. TC was also significantly higher in MYH7mut at submaximal, more physiological [Ca(2+)]. EW was significantly lower in both mutation carrier groups, while MVO2 did not differ. MEE was significantly lower in both mutation carrier groups compared with controls, showing the lowest efficiency in MYH7 mutation carriers. CONCLUSION: We provide direct evidence that sarcomere mutations perturb the energetic cost of cardiac contraction. Gene-specific severity of cardiac abnormalities may underlie differences in disease onset and suggests that early initiation of metabolic treatment may be beneficial, in particular, in MYH7 mutation carriers.

Myocardial infarct heterogeneity assessment by late gadolinium enhancement cardiovascular magnetic resonance imaging shows predictive value for ventricular arrhythmia development after acute myocardial infarction.

AIMS: The aim of this study was to assess the association between the proportions of penumbra-visualized by late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR)-after acute myocardial infarction (AMI) and the prevalence of ventricular tachycardia (VT). METHODS: One-hundred and sixty-two AMI patients, successfully, treated by primary percutaneous coronary intervention (PCI) underwent LGE-CMR after a median of 3 days (3-4) and 24-h Holter monitoring after 1 month. With LGE-CMR, the total amount of enhanced myocardium was quantified and divided into an infarct core (>50% of maximal signal intensity) and penumbra (25-50% of maximal signal intensity). With Holter monitoring, the number of VTs (≥4 successive PVCs) per 24 h was measured. RESULTS: The mean total enhanced myocardium was 31 ± 11% of the left ventricular mass. The % penumbra accounted for 39 ± 11% of the total enhanced area. In 29 (18%) patients, Holter monitoring showed VT, with a median of 1 episode (1-3) in 24 h. A larger proportion of penumbra within the enhanced area increased the risk of VTs [OR: 1.06 (95% CI: 1.02-1.10), P = 0.003]. After multivariate logistic regression analysis, the presence of ventricular fibrillation before primary PCI [OR: 5.60 (95% CI: 1.54-20.29), P = 0.01] and the proportional amount of penumbra within the enhanced myocardium [OR: 1.06 (95% CI: 1.02-1.10), P = 0.04] were independently associated with VT on Holter monitoring. CONCLUSION: Larger proportions of penumbra in the subacute phase after AMI are associated with increased risk of developing VTs. Quantification of penumbra size may become a useful future tool for risk stratification and ultimately for the prevention of ventricular arrhythmias.

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry. METHODS: Thirty-five qualitative criteria were defined (scores 0-3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student. RESULTS: The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0-2 for SNR <2, 2-5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0-2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83. CONCLUSIONS: The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.

Comparison of three-dimensional echocardiographic software packages for assessment of left ventricular mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy.

AIMS: We directly compared TomTec and QLAB software packages for the three-dimensional echocardiographic (3DE) assessment of left ventricular (LV) dyssynchrony including their ability to predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic and non-ischaemic cardiomyopathy. METHODS AND RESULTS: A total of 140 heart failure patients with the LVEF ≤35% and 60 healthy volunteers underwent 3DE. A subgroup of 60 patients underwent CRT and were evaluated before and 6-12 months after implantation. The systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume for all 16 LV segments and measured with both software packages and compared using Pearson's correlation and Bland-Altman analysis. Measurements of SDI were significantly higher using TomTec compared with QLAB in both patients (10.9 ± 3.8 vs. 9.7 ± 3.9, P < 0.001) and healthy volunteers (4.1 ± 0.8 vs. 2.4 ± 1, P < 0.001), with large biases and wide limits of agreement. A moderate correlation (r = 0.65, P < 0.001) was observed between both software packages in patients while their inter-observer and intra-observer reliability were good. Of the 60 patients undergoing CRT, reverse remodelling as a measure of response was observed in 41 patients (68%). The optimal SDI cut-off value to predict response to CRT was higher for TomTec than for QLAB (8.8 vs.7.3%, P < 0.001) and demonstrated better sensitivity and specificity (93 and 61%, respectively) compared with QLAB (88 and 33%, respectively). Response prediction in patients with non-ischaemic cardiomyopathy was excellent with a sensitivity and specificity of 95 and 100% for TomTec and 70 and 83% for QLAB using similar cut-off values of 9.1 and 9.2%, respectively. CONCLUSION: Different 3DE software packages for the assessment of mechanical dyssynchrony should not be used interchangeably until better software standardization is achieved. Dyssynchrony assessment with 3DE for the prediction of response to CRT seems particularly useful in patients with non-ischaemic cardiomyopathy.

A meta-analysis of left ventricular dyssynchrony assessment and prediction of response to cardiac resynchronization therapy by three-dimensional echocardiography.

AIMS: In a time of controversy regarding the use of echocardiography for assessment of left ventricular (LV) dyssynchrony and prediction of response to cardiac resynchronization therapy (CRT), this meta-analysis aimed to evaluate the feasibility and reliability of LV dyssynchrony assessment by three-dimensional echocardiography (3DE), determine clinically useful reference values in healthy subjects and heart failure patients, and examine the accuracy of 3DE to predict response to CRT. METHODS AND RESULTS: A total of 73 studies that evaluated the assessment of LV dyssynchrony by 3DE were eligible. The systolic dyssynchrony index (SDI) for 16 segments, being the predominant 3DE dyssynchrony parameter, was used for data pooling. Results demonstrated that LV dyssynchrony assessment by 3DE is feasible in 94% of studied subjects [95% confidence interval (CI): 92-95%)]. Pooled estimates of intraclass correlation coefficients (ICC) and limits of agreement (LoA) demonstrated that SDI has good interobserver (ICC: 0.92, LoA: 4.07%) and intraobserver reliability (ICC: 0.95, LoA: 2.10%). Reference values of SDI in healthy subjects, heart failure patients in general, and patients eligible for CRT were 2.7 ± 0.9%, 9.8 ± 3.9%, and 10.7 ± 3.6%, respectively. Meta-regression analysis demonstrated that reference values of SDI in healthy subjects significantly differed between different software [1.80% (95% CI: 0.55-3.05%), P< 0.001]. In patients eligible for CRT, SDI had good accuracy to predict treatment response with a weighted mean cut-off value of 9.8% and pooled estimates for sensitivity and specificity of 93% (95% CI: 89-97%) and 75% (95% CI: 58-93%), respectively. CONCLUSION: 3DE is a feasible and reliable tool for assessment of LV dyssynchrony and may have additional value to current selection criteria for accurate prediction of response to CRT.

Prognostic value of routine cardiac magnetic resonance assessment of left ventricular ejection fraction and myocardial damage: an international, multicenter study.

BACKGROUND: Cardiac magnetic resonance (CMR) is considered the reference standard for assessment of left ventricular ejection fraction (LVEF) and myocardial damage. However, few studies have evaluated the relationship between CMR findings and patient outcome, and of these, most are small and none multicenter. We performed an international, multicenter study to assess the prognostic importance of routine CMR in patients with known or suspected heart disease. METHODS AND RESULTS: From 10 centers in 6 countries, consecutive patients undergoing routine CMR assessment of LVEF and myocardial damage by cine and delayed-enhancement imaging (DE-CMR), respectively, were screened for enrollment. Clinical data, CMR protocol information, and findings were collected at all sites and submitted to the data coordinating center for verification of completeness and analysis. The primary end point was all-cause mortality. A total of 1560 patients (age, 59±14 years; 70% men) were enrolled. Mean LVEF was 45±18%, and 1049 (67%) patients had hyperenhanced tissue (HE) on DE-CMR indicative of damage. During a median follow-up time of 2.4 years (interquartile range, 1.2, 2.9 years), 176 (11.3%) patients died. Patients who died were more likely to be older (P<0.0001), have coronary disease (P=0.004), have lower LVEF (P<0.0001), and have more segments with HE (P<0.0001). In multivariable analysis, age, LVEF, and number of segments with HE were independent predictors of mortality. Among patients with near-normal LVEF (≥50%), those with above-median HE (>4 segments) had reduced survival compared to patients with below- or at-median HE (P=0.02). CONCLUSIONS: Both LVEF and amount of myocardial damage as assessed by routine CMR are independent predictors of all-cause mortality. Even in patients with near-normal LVEF, significant damage identifies a cohort with a high risk for early mortality.

Three-dimensional speckle tracking echocardiography for automatic assessment of global and regional left ventricular function based on area strain.

OBJECTIVE: We evaluated the ability of a novel automatic index based on area strain to reliably quantify global and regional left ventricular (LV) function and accurately identify wall motion (WM) abnormalities using three-dimensional speckle tracking echocardiography. METHODS: A total of 140 consecutive patients underwent two- and three-dimensional echocardiography. Segmental WM assessment by area strain was compared with visual assessment of two-dimensional images by two experienced echocardiographers. For global LV function assessment, area strain was validated against LV ejection fraction (EF) and wall motion score index (WMSI). Observer reliability was assessed in all patients, whereas test-retest reliability was evaluated in a subgroup of 50 randomly selected patients. Normal reference values of area strain were determined in 56 healthy subjects. RESULTS: Agreement of WM scores between area strain and visual assessment was found in 94% of normal, 55% of hypokinetic, and 91% of akinetic segments (κ-coefficient 0.88). Sensitivity, specificity, and accuracy of area strain to distinguish abnormal segments from normal segments were 91%, 96%, and 94%, respectively. In regard to global LV function assessment, area strain was highly correlated with EF and WMSI (r = 0.91 and 0.88, respectively). Observer and test-retest reliability of area strain for quantitative assessment of global and regional LV function were good to excellent (all intraclass correlation coefficients ≥0.77). Intraobserver and interobserver reliability of semiquantitative segmental WM analysis by area strain (κ-coefficients 0.87 and 0.73) were comparable to visual assessment by experienced echocardiographers (0.85 and 0.69, respectively). CONCLUSION: Area strain represents a promising novel automatic index that may provide an accurate and reproducible alternative to current echocardiographic standards for quantitative assessment of global and regional LV function. Area strain seems to adequately identify regional wall motion abnormalities compared with the clinical standard of visual assessment by experienced echocardiographers.

Value and limitations of electromechanical endocardial mapping in the assessment of global and regional left ventricular function and transmural extent of infarction: a comparison with cardiovascular magnetic resonance.

AIMS: To determine the relation between electromechanical endocardial mapping (EEM) and cardiac magnetic resonance (CMR) derived functional and viability parameters in patients with a large myocardial infarction. METHODS AND RESULTS: Forty-two patients with a large ST-elevation myocardial infarction underwent both EEM and CMR four months after primary percutaneous coronary intervention. EEM was performed to assess linear local shortening (LLS), unipolar voltage (UV) and bipolar voltage (BV). CMR cine imaging was performed to determine left ventricular global volumes, ejection fraction and regional function. Late gadolinium enhancement was used to assess size and transmural extent of infarction. Average LLS, UV and BV differed significantly between normal and dysfunctional segments (9.8 vs. 7.3, 11.8 vs. 9.7 and 3.3 vs. 2.8 for LLS, UV and BV respectively; p<0.001 for LLS and UV, p=0.006 for BV). In addition, average LLS, UV and BV, differed significantly between non-, subendocardial and transmural enhanced segments (10.8 vs. 8.8 vs. 5.0, 12.3 vs. 10.5 vs. 9.5 and 3.5 vs. 3.0 vs. 2.3 for LLS, UV and BV, respectively, p<0.001 for all variables). Although regional EEM data showed reasonable correlation with CMR, specific cut-off values for EEM parameters could not be established. CONCLUSIONS: EEM may be helpful in determining both the regional function and the transmural extent of infarction in patients with a large myocardial infarction. However, correlation with CMR parameters was moderate and exact cut-off values for EEM parameters could not be established. Further development of this potentially very useful modality is needed before it can be advocated for exact border-zone endocardial injection.

How do hypertrophic cardiomyopathy mutations affect myocardial function in carriers with normal wall thickness? Assessment with cardiovascular magnetic resonance.

BACKGROUND: Clinical data on myocardial function in HCM mutation carriers (carriers) is sparse but suggests that subtle functional abnormalities can be measured with tissue Doppler imaging before the development of overt hypertrophy. We aimed to confirm the presence of functional abnormalities using cardiovascular magnetic resonance (CMR), and to investigate if sensitive functional assessment could be employed to identify carriers. RESULTS: 28 carriers and 28 controls were studied. Global left atrial (LA) and left ventricular (LV) dimensions, segmental peak systolic circumferential strain (SCS) and peak diastolic circumferential strain rate (DCSR), as well as the presence of late Gadolinium enhancement (LGE) were determined with CMR. Septal and lateral myocardial velocities were measured with echocardiographic tissue Doppler imaging. LV mass and volumes were comparable between groups. Maximal septal to lateral wall thickness ratio (SL ratio) was larger in carriers than in controls (1.3+/-0.2 versus 1.1+/-0.1, p<0.001). Also, LA volumes were larger in carriers compared to controls (p<0.05). Both peak SCS (p<0.05) and peak DCSR (p<0.01) were lower in carriers compared to controls, particularly in the basal lateral wall. Focal LGE was present in 2 carriers and not in controls. The combination of a SL ratio>1.2 and a peak DCSR<105%.s-1 was present in 45% of carriers and in none of the controls, yielding a positive predictive value of 100%. Two carriers and 18 controls had a SL ratio<1.2 and peak DCSR>105%.s-1, yielding a negative predictive value of 90%. With multivariate analysis, HCM mutation carriership was an independent determinant of reduced peak SCS and peak DCSR. CONCLUSIONS: HCM mutation carriership is an independent determinant of reduced peak SCS and peak DCSR when LV wall thickness is within normal limits, and is associated with increased LA volumes and SL ratio. Using SL ratio and peak DCSR has a high accuracy to identify carriers. However, since carriers also display structural abnormalities and focal LGE, we advocate to also evaluate morphology and presence of LGE when screening for carriers.

Assessment of intraventricular mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy: comparison between tissue Doppler imaging and real-time three-dimensional echocardiography.

OBJECTIVE: We studied the comparability of left ventricular (LV) mechanical dyssynchrony assessment by tissue Doppler imaging (TDI) and real-time three-dimensional echocardiography (RT3DE) in patients with a wide range of LV ejection fractions and different causes of cardiomyopathy. In addition, we evaluated the ability of both techniques to predict response to cardiac resynchronization therapy (CRT). METHODS: A total of 90 patients and 30 healthy volunteers underwent both TDI and RT3DE. A subgroup of 27 patients underwent CRT and were evaluated before and 6 months after implantation. Mechanical dyssynchrony was measured with TDI using the standard deviation of time to peak systolic tissue velocity of 12 LV myocardial segments. With RT3DE, the standard deviation of time from QRS onset to minimal volume of 16 LV subvolumes was assessed. Indicators of response to CRT were a clinical improvement of >or= 1 New York Heart Association functional class, and reverse remodeling defined as a reduction of >or= 15% in LV end-systolic volume at 6 months. RESULTS: A moderate correlation (r = 0.581, P < .001) was observed between TDI and RT3DE. No significant difference in the presence of mechanical dyssynchrony by TDI and RT3DE was observed (53% vs 48%, respectively). Agreement between techniques was comparable between patients with ischemic and nonischemic cardiomyopathy. However, up to 30% nonagreement between the 2 techniques was found, depending on the severity of LV dysfunction. Of the 27 patients undergoing CRT, clinical response was observed in 70% of patients, whereas reverse remodeling occurred in 63% of patients. All baseline characteristics were similar between responders and nonresponders, except for mechanical dyssynchrony assessed by RT3DE, which was significantly higher in responders compared with nonresponders (10.1% +/- 2.6% vs 5.1% +/- 1.2% for clinical response, P < .001; 10.0% +/- 2.8% vs 6.3% +/- 2.3% for reverse remodeling, P = .001). By applying previously defined cutoff values, receiver operating characteristic curve analysis demonstrated a sensitivity of 58% with a specificity of 50% for TDI and a sensitivity of 95% with a specificity of 87% for RT3DE to predict clinical response to CRT. For prediction of reverse remodeling after CRT, sensitivity and specificity were 59% and 50% for TDI, and 88% and 60% for RT3DE, respectively. The optimal cutoff value for systolic dyssynchrony index by RT3DE of 6.7% yielded a sensitivity of 90% with a specificity of 87% to predict clinical response, and a sensitivity of 88% with a specificity of 70% to predict reverse remodeling. CONCLUSION: Marked differences between techniques are found for the presence of mechanical dyssynchrony when current cutoff values are applied, making interchangeability of these techniques uncertain. Assessment of mechanical dyssynchrony by RT3DE might be an appropriate alternative to TDI for accurate prediction of response to CRT.

Quantification of late gadolinium enhanced CMR in viability assessment in chronic ischemic heart disease: a comparison to functional outcome.

BACKGROUND: Quantification of late gadolinium enhanced cardiovascular magnetic resonance (LGE CMR) by objective window setting increases reproducibility and facilitates multicenter comparison and cooperation. So far, quantification methods or models have only been validated to postmortem animal studies. This study was undertaken to evaluate quantification of LGE in relation to the clinical standard of viability, i.e. functional outcome after revascularization.Thirty-eight patients with chronic ischemic myocardial dysfunction underwent cine and LGE 1 month before and cine CMR 6 months after coronary revascularization. Enhancement was quantified by thresholding window setting at: 2-8 SD above mean signal intensity of a remote normal region, and according to the full width at half maximum method (FWHM). Dysfunctional segments were divided in 5 groups according to segmental extent of enhancement (SEE): SEE 1--no enhancement to SEE 5--76-100% with each quantification method. RESULTS: Quantification methods had a strong influence on SEE and total infarct size. Multilevel analysis showed that thresholding contrast images at 6 SD best predicted segmental functional outcome after revascularization, but the difference with other methods was small and non-significant. CONCLUSION: Simple thresholding techniques strongly influence global and segmental extent of LGE, but have relatively little influence on the accuracy to predict segmental functional improvement after revascularization.

Assessment of microvascular obstruction and prediction of short-term remodeling after acute myocardial infarction: cardiac MR imaging study.

PURPOSE: To evaluate which cardiac magnetic resonance (MR) imaging technique for detection of microvascular obstruction (MVO) best predicts left ventricular (LV) remodeling after acute myocardial infarction (MI). MATERIALS AND METHODS: This study had local ethics committee approval; all patients gave written informed consent. Sixty-three patients with first acute MI, treated with primary stent placement and optimal medical therapy, underwent cine MR imaging at 4-7 days and at 4 months after MI. Presence of MVO was qualitatively evaluated at baseline by using three techniques: (a) a single-shot saturation-recovery gradient-echo first-pass perfusion sequence (early hypoenhancement), mean time, 1.09 minutes +/- 0.07 (standard deviation) after contrast material administration; (b) a three-dimensional segmented saturation-recovery gradient-echo sequence (intermediate hypoenhancement), mean time, 2.17 minutes +/- 0.26; and (c) a two-dimensional segmented inversion-recovery gradient-echo late gadolinium enhancement sequence (late hypoenhancement), mean time, 13.32 minutes +/- 1.26. Contrast-to-noise ratios (CNRs) were calculated from the signal-to-noise ratios of the infarcted myocardium and MVO areas. Univariable linear regression analysis was used to identify the predictive value of each MR imaging technique. RESULTS: Early hypoenhancement was detected in 44 (70%) of 63 patients; intermediate hypoenhancement, in 39 (62%); and late hypoenhancement, in 37 (59%). Late hypoenhancement was the strongest predictor of change in LV end-diastolic and end-systolic volumes over time (beta = 14.3, r = 0.40, P = .001 and beta = 11.3, r = 0.44, P < .001, respectively), whereas intermediate and late hypoenhancement had comparable predictive values of change in LV ejection fraction (beta = -3.1, r = -0.29, P = .02 and beta = -2.8, r = -0.27, P = .04, respectively). CNR corrected for spatial resolution was significantly superior for late enhancement compared with the other sequences (P < .001). CONCLUSION: By using cardiac MR imaging, late hypoenhancement is the best prognostic marker of LV remodeling, with highest CNR between the infarcted myocardium and MVO regions.

Semi-quantitative assessment of right ventricular function in comparison to a 3D volumetric approach: a cardiovascular magnetic resonance study.

Right ventricular (RV) volume measurements with cardiovascular magnetic resonance (CMR) is considered the gold standard, but acquisition and analysis remain time-consuming. The aim of our study was therefore to investigate the accuracy and performance of a semi-quantitative assessment of RV function in CMR, compared to the standard quantitative approach. Seventy-five subjects with pulmonary hypertension (15), anterior myocardial infarction (15), inferior myocardial infarction (15), Brugada syndrome (15) and normal subjects (15) underwent cine CMR. RV end-systolic and end-diastolic volumes were determined to calculate RV ejection fraction (EF). Four-chamber cine images were used to measure tricuspid annular plane systolic excursion (TAPSE). RV fractional shortening (RVFS) was calculated by dividing TAPSE by the RV end-diastolic length. RV EF correlated significantly with TAPSE (r = 0.62, p < 0.01) and RVFS (r = 0.67, p < 0.01). Sensitivity to predict RV dysfunction was comparable between TAPSE and RVFS, with higher specificity for RVFS, but comparable areas under the ROC curve. Intra- and inter-observer variability of RV EF was better than TAPSE (3%/4% versus 7%/15%, respectively). For routine screening in clinical practice, TAPSE and RVFS seem reliable and easy methods to identify patients with RV dysfunction. The 3D volumetric approach is preferred to assess RV function for research purposes or to evaluate treatment response.

Relation between the assessment of microvascular injury by cardiovascular magnetic resonance and coronary Doppler flow velocity measurements in patients with acute anterior wall myocardial infarction.

OBJECTIVES: We studied the relation between presence and severity of microvascular obstruction (MO), measured by cardiovascular magnetic resonance (CMR) and intracoronary Doppler flow measurements, for assessment of myocardial reperfusion in patients with acute anterior myocardial infarction (MI) treated by primary percutaneous coronary intervention (PCI). BACKGROUND: Cardiovascular magnetic resonance has been used to detect and quantify MO in patients after acute MI but has never been compared with coronary blood flow velocity patterns. METHODS: Twenty-seven patients with first anterior ST-segment elevation MI successfully treated with primary PCI were included. Coronary blood flow velocity was measured during recatheterization 4 to 8 days after primary PCI. These measurements were related to MO determined by late gadolinium-enhanced (LGE) CMR performed the day before recatheterization. RESULTS: Early systolic retrograde flow was observed in 0 of 8 patients without MO on LGE CMR and in 10 (53%) of 19 patients with MO (p = 0.01). The extent of MO correlated with the diastolic-systolic velocity ratio (r = 0.44; p = 0.02), diastolic deceleration time (r = -0.61; p = 0.001), diastolic deceleration rate (r = 0.75; p < 0.0001), and coronary flow velocity reserve of the infarct-related artery (r = -0.44; p = 0.02). Furthermore, multivariate regression analyses, including extent of MO, infarct size, and transmural necrosis on LGE CMR, revealed that extent of MO was the only independent factor related to early systolic retrograde flow and diastolic deceleration rate. CONCLUSIONS: Assessment of microvascular injury by LGE CMR corresponds well to evaluation by intracoronary Doppler flow measurements. By means of CMR, quantification of myocardial function, infarct size, and microvascular injury can accurately be performed with a single noninvasive technique in patients with acute MI.