Mitral annular disjunction; how accurate are we? A cardiovascular MRI study defining risk.

Aims: Mitral Annular Disjunction (MAD) refers to embryologic fibrous separation between mitral annular ring and basal left ventricular myocardium. Since its original description, the role of MAD in arrhythmic mitral valve prolapse (MVP) has been the subject of active research. In this study we sought to assess prognostic and imaging characteristics of MVP patients with and without underlying MAD. Methods and results: Patients with posterior or bi-leaflet MVP were retrospectively identified via a review of all patients referred to our cardiac magnetic resonance (CMR) imaging laboratory from January 2015 to May 2022. MVP patients were further stratified by underlying MAD status. A total of 100 MVP patients undergoing CMR imaging (52 MVP patients with posterior MAD) were retrospectively identified with female comprising 55 % of the cohort. MVP patients with MAD were more likely to have an abnormal basal inferolateral/ papillary muscles LGE (51 % vs 21 %, p < 0.01). Posterior MAD longitudinal disjunction gap in 'mm' was a predictor of ventricular tachycardia (VT) [1.29, p = 0.01)]. Using ROC curve analysis, a disjunction gap of ≥ 4 mm was predictive of VT (AUC-0.71, p < 0.01), and incorporation of LGE in ROC model further improved AUC to 0.78 confirmed via Akaike information criterion (p < 0.01). Conclusion: Abnormal LGE involving basal inferolateral myocardium and papillary muscles may provide etiologic substrate for arrythmia in MVP patients.

The sine transform is the sine qua non of the pulmonary and systemic pressure relationship.

Assessment of therapeutic interventions in patients with pulmonary arterial hypertension (PAH) suffers from several commonly encountered limitations: (1) patient studies are often too small and short-term to provide definitive conclusions, (2) there is a lack of a universal set of metrics to adequately assess therapy and (3) while clinical treatments focus on management of symptoms, there remain many cases of early loss of life in a seemingly arbitrary distribution. Here we provide a unified approach to assess right and left pressure relationships in PAH and pulmonary hypertension (PH) patients by developing linear models informed by the observation of Suga and Sugawa that pressure generation in the ventricle (right or left) approximately follows a single lobe of a sinusoid. We sought to identify a set of cardiovascular variables that either linearly or via a sine transformation related to systolic pulmonary arterial pressure (PAPs) and systemic systolic blood pressure (SBP). Importantly, both right and left cardiovascular variables are included in each linear model. Using non-invasively obtained cardiovascular magnetic resonance (CMR) image metrics the approach was successfully applied to model PAPs in PAH patients with an r2 of 0.89 (p < 0.05) and SBP with an r2 of 0.74 (p < 0.05). Further, the approach clarified the relationships that exist between PAPs and SBP separately for PAH and PH patients, and these relationships were used to distinguish PAH vs. PH patients with good accuracy (68%, p < 0.05). An important feature of the linear models is that they demonstrate that right and left ventricular conditions interact to generate PAPs and SBP in PAH patients, even in the absence of left-sided disease. The models predicted a theoretical right ventricular pulsatile reserve that in PAH patients was shown to be predictive of the 6 min walk distance (r2 = 0.45, p < 0.05). The linear models indicate a physically plausible mode of interaction between right and left ventricles and provides a means of assessing right and left cardiac status as they relate to PAPs and SBP. The linear models have potential to allow assessment of the detailed physiologic effects of therapy in PAH and PH patients and may thus permit cross-over of knowledge between PH and PAH clinical trials.

Propitious temporal changes in clinical outcomes after transcatheter compared to surgical aortic valve replacement; a meta-analysis of over 65,000 patients.

BACKGROUND: The treatment of symptomatic severe aortic stenosis (AS) has rapidly evolved over the past decade, in both transcatheter (TAVR) and surgical aortic valve replacement (SAVR), resulting in reported improved clinical outcomes. Operator experience and technical improvements have improved outcomes especially for patients undergoing TAVR. We sought to determine and compare 1-year outcomes using a contemporary meta-analysis. METHOD: We searched the Medline (MESH), Cochrane and Google scholar databases using keywords "AS", "atrial fibrillation" (AFib) and "stroke". We performed a meta-analysis to compare TAVR with SAVR populations for post-procedural stroke, all-cause and cardiovascular mortality at 1-year. RESULTS: A total of 23 studies met criteria for analysis with total population of 66,857 patients, of which 61,913 had TAVR and 4944 had SAVR. Temporal trends demonstrated overall improvement in outcome for both, TAVR and SAVR groups through the decade. Outcomes, in terms of stroke (3.1% vs. 5%), all-cause (12.4% vs. 10.3%) and cardiovascular mortality (7.2% vs. 6.2%) were similar at 1-year, in TAVR versus SAVR, respectively. CONCLUSION: Despite overall gradual improvement in both TAVR and SAVR outcomes over the decade, there is a statistical overlap in confidence intervals for all-cause, cardiovascular mortality and postprocedural stroke at 1-year. While 23 individual studies demonstrate considerable advantages of each technique in certain cohorts, integrating over 65,000 pts with our stratified surgical analysis suggests that TAVR is comparable to SAVR for low and intermediate risk population while superior to SAVR only in the highest-risk population for short and intermediate term outcomes. This has substantial socio-economic implications as we contemplate expanding our TAVR indications to low/intermediate risk populations.

A Model Incorporating Left Ventricular Impedance Index may be Explanatory for Late Pulmonary Vein Isolation Failure.

Objective: To study the influence of a flow-based Impedance Index to attempt to explain the persistent late failure rate of Pulmonary Vein Isolation (PVI) in patients with Atrial Fibrillation (AF). Background: We recently described a flow-based Impedance Index for left ventricular ejection into the aorta and noted an association with Major Adverse Cardiovascular Event Rate (MACE). While the Impedance Index is not routinely measured in PVI patients it approximates to measures derivable from the left ventricular ejection fraction (EF). We sought to assess the Impedance Index's influence on PVI failure rate in combination with indices of left atrial size. Methods: In AF patients (n=100) undergoing a Cardiovascular Magnetic Resonance (CMR) imaging examination prior to undergoing PVI we assessed baseline characteristics for their influence on the PVI failure rate at 3-12 months. Uni-variable and multi-variable binary logistic models were performed to find predictors of the PVI failure rate at follow-up. Results: All patients underwent PVI and CMR imaging. A total of 26 (26%) patients had late AF recurrence at 3-12 months follow-up. Multi-variable models that predicted PVI failure were: 1) the baseline Impedance Index and LA volume index (p<0.05) and 2) the baseline Impedance Index and the degree of mitral valve regurgitation (MR) (p<0.001). While the Impedance Index was derived from EF, EF per se was not a predictor of PVI failure (p=0.28). Conclusions: We have provided evidence of the influence of a flow-based Impedance Index on the PVI late failure rate which is significant and remains explanatory when adjusting for measures of atrial size, MR grade and LA volume index. Direct measure of the Impedance Index was not available here and was derived from EF measures. Further work is needed to directly measure the Impedance Index in a PVI population and determine the mechanism for the influence on PVI failure, which may lead to modification of the ablation procedure to improve the success rate.

Integrated use of cardiac MRI and the CardioMEMS™ HF system in PAH: the utility of coincident pressure and volume in RV failure-the NHLBI-VITA trial.

BACKGROUND: This study aims to study the feasibility and safety of measuring volumetric and pressure parameters noninvasively using simultaneous cardiovascular magnetic resonance (cMR) volumetric data and time-resolved pressure waveforms from previously implanted CardioMEMS devices in pulmonary arterial hypertension (PAH) patients. Opportunities to intervene during clinically occult phases in PAH promise to herald a key transformation in our current practice for treating this complex population. Currently, it is possible and convenient to monitor daily pulmonary arterial (PA) pressures in PAH patients using the CardioMEMS device to determine clinically silent progression. Supplementation of these pressures with other prognostic measurements of right ventricular (RV) contractility, PA resistance and RV/PA coupling could add further predictive capabilities. METHODS: PAH patients (n=17) with New York Hospital Association (NYHA) class III or IV heart failure (HF) and recent HF related hospitalizations were implanted with the CardioMEMS device as part of a NHLBI sponsored Trial. Implanted patients were then assessed using cMR imaging of the right ventricle (RV) along with measurement of pulmonary artery flow. Patients were imaged at one-month post implant (baseline) and at 4-month follow-up time (n=12). At baseline, patients were studied at rest and then under three different physiologic conditions: inhaled nitric oxide (INO), dobutamine (Dob) stress and volumetric stress (Vol), using a multiple slice short-axis imaging and a rapid imaging protocol. RESULTS: All patients were safely imaged, with no artifacts obscuring the cMR images. RV volumes were measured successfully at rest and under each stress condition using a reduced scan approach that required calibration for each patient which achieved a correlation r2 of 0.98. Variables measured included the maximal pulmonary artery elastance (Ea), maximal RV myocardial elastance (Emax) and ventricular-vascular coupling ratio (VVC). The response to stressors was determined on a patient basis. No complications occurred during the cMRI examination. CONCLUSIONS: It is safe and feasible to perform cMR imaging with simultaneous pulmonary artery pressure readings from the CardioMEMS device. A reduced scan approach was developed to allowed measurement of RV volumes during stress conditions. Volumetric and pressure measurements can be combined to assess fundamental myocardial properties (e.g., Emax, Ea and VVC) in PAH patients serially over time. In the future, these parameters can be tested as serial predictors of outcome and response to therapies in PAH.

Pulmonary vein remodeling following pulmonary vein isolation in patients with atrial fibrillation-do pulmonary veins represent only an epiphenomenon? A cardiac MRI study.

BACKGROUND: After successful pulmonary vein isolation (PVI) for atrial fibrillation (AF), the left atrium (LA) undergoes reverse remodeling. However, few studies have directly studied pulmonary vein (PV) remodeling and focused on whether pre PVI-PV conditions could predict outcome of the procedure. We hypothesize that: (I) post PVI, in addition to LA remodeling the PVs undergo a parallel degree of remodeling; and (II) that PV characteristics pre PVI can be used to identify patients more likely to sustain normal sinus rhythm (NSR). METHODS: Patients (n=100) scheduled for PVI had a cardiovascular magnetic resonance (CMR) imaging before and 6±2 months following PVI. PV cross sectional areas (CSA) within 0.5 cm of the ostium and LA volumes were measured. Patients were categorized as responders (R) or non-responders (NR), based on two separate 14-day Holter monitoring. RESULTS: PVs CSA were significantly reduced post procedure in both groups, R (233±53 to 192±52 mm2, P<0.001) and NR (241±54 to 207±44 mm2, P<0.001), however, the difference between R and NR post PVI was not significant (192±52 to 207±44 mm2, P=0.19). Reduction in PVs CSAs post procedure moderately correlated with the 3D LA volume reduction (r=0.48, P<0.001). CONCLUSIONS: PVs mirror the LA in that they significantly change in size following PVI yet they were not found to directly predict maintenance of NSR.

Improved approach to quantitative cardiac volumetrics using automatic thresholding and manual trimming: a cardiovascular MRI study.

To establish the clinical validity and accuracy of automatic thresholding and manual trimming (ATMT) by comparing the method with the conventional contouring method for in vivo cardiac volume measurements. CMR was performed on 40 subjects (30 patients and 10 controls) using steady-state free precession cine sequences with slices oriented in the short-axis and acquired contiguously from base to apex. Left ventricular (LV) volumes, end-diastolic volume, end-systolic volume, and stroke volume (SV) were obtained with ATMT and with the conventional contouring method. Additionally, SV was measured independently using CMR phase velocity mapping (PVM) of the aorta for validation. Three methods of calculating SV were compared by applying Bland-Altman analysis. The Bland-Altman standard deviation of variation (SD) and offset bias for LV SV for the three sets of data were: ATMT-PVM (7.65, [Formula: see text]), ATMT-contours (7.85, [Formula: see text]), and contour-PVM (11.01, 4.97), respectively. Equating the observed range to the error contribution of each approach, the error magnitude of ATMT:PVM:contours was in the ratio 1:2.4:2.5. Use of ATMT for measuring ventricular volumes accommodates trabeculae and papillary structures more intuitively than contemporary contouring methods. This results in lower variation when analyzing cardiac structure and function and consequently improved accuracy in assessing chamber volumes.

Aortic flow conditions predict ejection efficiency in the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: The Windkessel model of the cardiovascular system, both in its original wind-chamber and flow-pipe form, and in its electrical circuit analog has been used for over a century to modeled left ventricular ejection conditions. Using parameters obtained from aortic flow we formed a Flow Index that is proportional to the impedance of such a "circuit". We show that the impedance varies with ejection fraction (EF) in a manner characteristic of a resonant circuit with multiple resonance points, with each resonance point centrally located in a small range of EF values, i.e., corresponding to multiple contiguous EF bands. METHODS: Two target populations were used: (I) a development group comprising male and female subjects (n=112) undergoing cardiovascular magnetic resonance (CMR) imaging for a variety of cardiac conditions. The Flow Index was developed using aortic flow data and its relationship to left ventricular EF was shown. (II) An illustration group comprised of female subjects from the Women's Ischemia Syndrome Evaluation (WISE) (n=201) followed for 5 years for occurrence of major adverse cardiovascular events (MACE). Flow data was not available in this group but since the Flow Index was related to the EF we noted the MACE rate with respect to EF. RESULTS: The EFs of the development population covered a wide range (9%-76%) traversing six Flow Index resonance bands. Within each Flow Index resonance band the impedance varied from highly capacitive at the lower range of EF through minimal impedance at resonance, to highly inductive at the higher range of EF, which is characteristic of a resonant circuit. When transitioning from one EF band to a higher band, the Flow Index made a sudden transition from highly inductive to capacitive impedance modes. MACE occurred in 26 (13%) of the WISE (illustration) population. Distance in EF units (Deltacenter) from the central location between peaks of MACE activity was derived from EF data and was predictive of MACE rate with an area under the receiver operator curve of 0.73. Of special interest, Deltacenter was highly predictive of MACE in the sub-set of women with EF >60% (AUC 0.79) while EF was no more predictive than random chance (AUC 0.48). CONCLUSIONS: A Flow Index that describes impedance conditions of left ventricular ejection can be calculated using data obtained completely from the ascending aorta. The Flow Index exhibits a periodic variation with EF, and in a separate illustration population the occurrence of MACE was observed to exhibit a similar periodic variation with EF, even in cases of normal EF.

Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE).

BACKGROUND: We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. METHODS: Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRIQL) and semi-quantitatively (MRISQ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated "original". Two regression models designated "BIAS" models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38±14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery disease (CAD) and for prediction of MACE. RESULTS: Adverse events occurred in 14 (11%) women and CAD was present in 13 (10%). There was a positive correlation of maximum coronary artery stenosis and BIAS score for MRI and SPECT (P<0.001). Receiver operator characteristic (ROC) analysis was conducted and showed an increase in the area under the curve of the BIAS-augmented MPI interpretation of MACE vs. the original for MRISQ (0.78 vs. 0.54), MRIQL (0.78 vs. 0.64), SPECT (0.82 vs. 0.63) and the average of the three readings (0.80±0.02 vs. 0.60±0.05, P<0.05). CONCLUSIONS: Increasing values of the BIAS score generated by both MRI and SPECT corresponded to the increasing prevalence of CAD and MACE. The BIAS-augmented detection of ischemia better predicted MACE compared with the Original reading for the MPI data for both MRI and SPECT.

Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericarditis: A proof of concept study.

OBJECTIVE: Invasive cardiac catheterization is the venerable "gold standard" for diagnosing constrictive pericarditis. However, its sensitivity and specificity vary dramatically from center to center. Given the ability to unequivocally define segments of the pericardium with the heart via radiofrequency tissue tagging, we hypothesize that cardiac magnetic resonance has the capability to be the new gold standard. METHODS: All patients who were referred for cardiac magnetic resonance evaluation of constrictive pericarditis underwent cardiac magnetic resonance radiofrequency tissue tagging to define visceral-parietal pericardial adherence to determine constriction. This was then compared with intraoperative surgical findings. Likewise, all preoperative cardiac catheterization testing was reviewed in a blinded manner. RESULTS: A total of 120 patients were referred for clinical suspicion of constrictive pericarditis. Thirty-nine patients were defined as constrictive pericarditis positive solely via radiofrequency tissue-tagging cardiac magnetic resonance, of whom 21 were positive, 4 were negative, and 1 was equivocal for constrictive pericarditis, as defined by cardiac catheterization. Of these patients, 16 underwent pericardiectomy and were surgically confirmed. There was 100% agreement between cardiac magnetic resonance-defined constrictive pericarditis positivity and postsurgical findings. No patients were misclassified by cardiac magnetic resonance. In regard to the remaining constrictive pericarditis-positive patients defined by cardiac magnetic resonance, 10 were treated medically, declined, were ineligible for surgery, or were lost to follow-up. Long-term follow-up of those who were constrictive pericarditis negative by cardiac magnetic resonance showed no early or late crossover to the surgery arm. CONCLUSIONS: Cardiac magnetic resonance via radiofrequency tissue tagging offers a unique, efficient, and effective manner of defining clinically and surgically relevant constrictive pericarditis. Specifically, no patient who was identified with constriction via cardiac magnetic resonance underwent inappropriate sternotomy. However, catheterization had substantial and unacceptable false-positive and false-negative rates with important clinical ramifications.

Mid wall fibrosis on CMR with late gadolinium enhancement may predict prognosis for LVAD and transplantation risk in patients with newly diagnosed dilated cardiomyopathy-preliminary observations from a high-volume transplant centre.

BACKGROUND: Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high-risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration. METHODS: Over 49 consecutive months, 61 consecutives DCM patients were referred for standard CMR(1.5T, GE) to interrogate the LV pattern, distribution, and extent of LGE (MultiHance, Princeton, NJ). Inclusion criteria for a primary non-ischaemic DCM and EF <45% were met in 31 patients. DCM patients were categorized into: (i) presence of midwall LV stripe (+Stripe) and (ii) absence of midwall stripe (-Stripe) groups. Primary outcome was defined by the composite of death, need for LV assist device (LVAD), and urgent orthotopic cardiac transplantation (Tx) during a 12-month follow-up period. Kaplan-Meier survival analysis was conducted grouping patients by +Stripe and -Stripe. RESULTS: There were no differences between groups for demographics, blood pressure, labs, baseline LVEF, NYHA class, or invasive haemodynamics. There were 18 patients (58%) with +Stripe. Nine events occurred: seven patients required urgent Tx and/or LVAD implantation and two patients died. The +Stripe categorization strongly predicted the need for LVAD, urgent Tx surgery, and death (log-rank = 9, P = 0.002). All the events occurred in the +Stripe patients with no MACE experienced in the -Stripe group. The -Stripe group experienced marked signs of improvement in LVEF (P = 0.01) at follow-up. LVEDD was predictive of need for LVAD/Tx and death by univariate analysis. Otherwise, no common clinical metric such as LVEF, LVEDV, RVEF, RVEDV, or any invasive haemodynamic parameter predicted MACE. CONCLUSIONS: The presence of +Stripe on CMR is strongly predictive of LVAD, transplant need, and death during a 12-month follow-up period in DCM patients in this proof of concept study. All -Stripe patients survived without experiencing any events. Incorporating CMR imaging into routine clinical practice may have prognostic value in DCM patients; indicating conservative management in low-risk patients while expectantly managing high-risk patients.

Magnetic resonance characterization of septal bounce: findings of blood impact physiology.

'Septal bounce' is a pathognomonic sign of constrictive pericarditis (CP). The objectives of the study are to resolve the etiology of the septal bounce, to generate septal bounce-related diagnostic tools, and to prove that its presence is related to the mechanical interaction between the atrioventricular inflow and the inter-ventricular septum. We compared steady state free precession four-chamber images between 11 CP patients and 11 controls via cardiac magnetic resonance. The septal bounce was composed of two movements observed during every cardiac cycle, simultaneous with the rapid filling and atrial systole respectively. Three parameters (measured at end-systole) were generated: right ventricular (RV) clamp (compression ratio of the RV)-greater in CP (0.88 ± 0.03) than controls (0.85 ± 0.03, p = 0.02), tri-septal angle between the tricuspid valve annulus plane and the interventricular septum (81° ± 9° vs. 91° ± 7°, p = 0.01), and impact angle between the tricuspid inflow vector and septum (8.6° ± 8.7° vs. 0° ± 6.6°, p = 0.01). The accuracy, positive predictive value, sensitivity and specificity of these parameters in differentiating CP from controls ranged from 100 to 82 %. A forth parameter-septal flow ratio, gauging the proportion of tricuspid inflow impacting the septum, was markedly higher in CP than controls (0.38 ± 0.19 vs. 0.01 ± 0.03, p < 0.0001) with 100 % sensitivity, specificity, positive and negative predictive value. The septal bounce consists of two sequential movements during each cardiac cycle, is time-related with the rapid ventricular filling and atrial systole, and likely represents a result of the tricuspid blood inflow impacting the interventricular septum. Four septal bounce-derived parameters have a good accuracy in differentiating CP from volunteers.

Ex vivo cardiovascular magnetic resonance measurements of right and left ventricular mass compared with direct mass measurement in excised hearts after transplantation: a first human SSFP comparison.

BACKGROUND: CMR is considered the 'gold standard' for non-invasive LV and RV mass quantitation. This information is solely based on gradient-recalled echo (GRE) sequences while contrast dependent on intrinsic T1/T2 characteristics potentially offers superior image contrast between blood and myocardium. This study aims, for the first time in humans, to validate the SSFP approach using explanted hearts obtained from heart transplant recipients. Our objective is establish the correlation between and to validate steady-state free precession (SSFP) derived LV and RV mass vs. autopsy mass of hearts from cardiac transplants patients. METHODS: Over three-years, 58 explanted cardiomyopathy hearts were obtained immediately upon orthotopic heart transplantation from the OR. They were quickly cleaned, prepared and suspended in a saline-filled container and scanned ex vivo via SSFP-SA slices to define LV/RV mass. Using an automatic thresholding program, segmentation was achieved in combination with manual trimming (ATMT) of extraneous tissue incorporating 3D cardiac modeling performed by independent and blinded readers. The explanted hearts were then dissected with the ventricles surgically separated at the interventricular septum. Weights of the total heart not excluding papillary and trabecular myocardium, LV and RV were measured via high-fidelity scale. Linear regression and Bland-Altman plots were used to analyze the data. The intra-class correlation coefficient was used to assess intra-observer reliability. RESULTS: Of the total of 58 explanted hearts, 3 (6%) were excluded due to poor image quality leaving 55 patients (94%) for the final analysis. Significant positive correlations were found between total 3D CMR mass (450 ± 111 g) and total pathology mass (445 ± 116 g; r = 0.99, p < 0.001) as well as 3D CMR measured LV mass (301 ± 93 g) and the pathology measured LV mass (313 ± 96 g; r = 0.95, p < 0.001). Strong positive correlations were demonstrated between the 3D CMR measured RV mass (149 ± 46 g) and the pathology measured RV mass (128 ± 40 g; r = 0.76, p < 0.001). The mean bias between 3D-CMR and pathology measures for total mass, LV mass and RV mass were: 3.0 g, -16 g and 19 g, respectively. CONCLUSIONS: SSFP-CMR accurately determines total myocardial, LV and RV mass as compared to pathology weighed explanted hearts despite variable surgical removal of instrumentation (left and right ventricular assist devices, AICD and often apical core removals). Thus, this becomes the first-ever human CMR confirmation for SSFP now validating the distinction of 'gold standard'.

Does the presence of Q waves on the EKG accurately predict prior myocardial infarction when compared to cardiac magnetic resonance using late gadolinium enhancement? A cross-population study of noninfarct vs infarct patients.

BACKGROUND: We hypothesize that infarct detection by electrocardiogram (EKG) is inaccurate as compared with detection by magnetic resonance imaging and is potentially independent of infarct vs noninfarct status. This might have implications for societies in which initial cardiovascular testing is uniformly EKG. OBJECTIVE: This study aimed to relate EKG-defined scar to cardiovascular magnetic resonance imaging (CMR)-defined scar independent of the underlying myocardial pathology. METHODS: A total of 235 consecutive patients who underwent CMR-late gadolinium enhancement (LGE) with simultaneous EKG were screened for Q waves and compared with patients with a positive LGE pattern. The patients were divided into 3 groups: (1) patients with a positive infarct LGE pattern (LGE+/+; herein defined as LGE+), (2) patients with a noninfarct LGE pattern (LGE+/-), and (3) patients with a negative LGE pattern (LGE-). RESULTS: While 139 of 235 patients (59%) were either LGE+ or LGE+/-, pathological Q waves were present in only 74 of 235 patients (31%). However, of these LGE+ or LGE+/- patients, only 76 (32%) had an infarct LGE pattern representing little overlap between the presence of LGE+ and Q waves. EKG sensitivity and specificity to detect infarct: 66% and 85%, respectively. However, of 24 of 74 patients (32%) with Q waves on the EKG, 66% were LGE+/- and 34% were LGE-. Importantly, 3-dimensional volume of myocardial scar was far more predictive of a Q wave than of scar transmurality. CONCLUSION: EKG-defined scar, while ubiquitous for an infarct, has low sensitivity than CMR-LGE-defined scar. Unexpectedly, a significant number of pathological Q waves had absent infarct etiology, indicating high false positivity. Similarly, underrecognition of bona fide myocardial infarction frequently occurs, while 3-dimensional CMR volume of myocardial scar is far more predictive of a Q wave than of scar transmurality. This suggests that the well-regarded EKG may be a disservice when applied on a population basis, leading to inappropriate over or under downstream testing with wide socioeconomic implications.

Left Ventricular Energy Model Predicts Adverse Events in Women With Suspected Myocardial Ischemia: Results From The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.

OBJECTIVES: To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. BACKGROUND: The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. METHODS: Women (n=227, mean age 59±12 years, range 31-86), with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n= 207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. RESULTS: Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, p<0.005) and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, p<0.005). The models remained predictive after adjustment for age, disease history and Framingham risk score. For each Cox model, patients were categorized as high-risk if the model hazard was positive and not high-risk otherwise. Kaplan-Meier analysis of time to MACE was performed for high-risk vs. not high-risk for MR (log rank 25.3, p<0.001) and gated SEPCT (log rank 18.2, p<001) models. CONCLUSIONS: Among women with suspected myocardial ischemia a high internal energy utilization has higher prognostic value than either a low EF or the presence of a myocardial perfusion defect assessed using two independent modalities of MR or gated SPECT.

Improved diagnosis and prognosis using Decisions Informed by Combining Entities (DICE): results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVES: To introduce an algorithmic approach to improve the interpretation of myocardial perfusion images in women with suspected myocardial ischemia. BACKGROUND: Gated single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) approaches have relatively poor diagnostic and prognostic value in women with suspected myocardial ischemia. Here we introduce an approach: Decisions Informed by Combining Entities (DICE) that forms a mathematical model utilizing MPI and cardiac dimensions generated by one modality to predict the perfusion status of another modality. The effect of the model is to systematically incorporate cardiac metrics that influence the interpretation of perfusion images, leading to greater consistency in designation of myocardial perfusion status between studies. METHODS: Women (n=213), with suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two modalities: gated SPECT (n=207) and MR imaging (n=203). To determine perfusion status, MR data were evaluated qualitatively and semi-quantitatively while SPECT data were evaluated using conventional clinical criteria. These perfusion status readings were designated "Original". Four regression models were generated to model perfusion status obtained with one modality [e.g., semi-quantitative magnetic resonance imaging (MRI)] against another modality (e.g., SPECT) and a threshold applied (DICE modeling) to designate perfusion status as normal or low. The DICE models included perfusion status, left ventricular (LV) chamber volumes and myocardial wall thickness. Women were followed for 40±16 months for the development of first major adverse cardiovascular event (MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for congestive heart failure). Original and DICE perfusion status were compared in their ability to detect high-grade coronary artery disease (CAD) and for prediction of MACE. RESULTS: Adverse events occurred in 25 (12%) women and CAD was present in 34 (16%). In receiver-operator characteristic (ROC) analysis for CAD detection, the average area under the curve (AUC) for DICE vs. Original status was 0.77±0.03 vs. 0.70±0.03, P<0.01. Similarly, in Kaplan-Meier survival analysis the average log-rank statistic was higher for DICE vs. the Original readings (10.6±5.2 vs. 3.0±0.6, P<0.05). CONCLUSIONS: While two data sets are required to generate the DICE models no knowledge of follow-up results is needed. DICE modeling improved diagnostic and prognostic value vs. the Original interpretation of the myocardial perfusion status.

LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association.

BACKGROUND: In patients with severe aortic stenosis (AS), long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR) offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability. HYPOTHESIS: We hypothesize that changes in LV structure and function following aortic valve replacement (AVR) are detectable by CMR and once triggered by AVR, continue for an extended period. METHODS: Twenty-four patients of which ten (67 ± 12 years, 6 female) with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured. RESULTS: All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m2, p < 0.005) and continued trending downwards through 4 years (127 ± 32 g/m2). Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p < 0.05)) and continued trending upwards, remaining stable through years 1-4 (66 ± 11 vs. 65 ± 9%). LVEDVI, initially high pre-AVR, decreased post-AVR (83 ± 30 to 68 ± 11 ml/m2, p < 0.05) trending even lower by year 4 (66 ± 10 ml/m2). LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p < 0.05) continuing to increase non-significantly through 4 years (49 ± 14 ml) with these LV metrics paralleling improvements in NYHA. However, LVmass/volume, a 3D measure of LV geometry, remained unchanged over 4 years. CONCLUSION: After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.

Prognostic value of global MR myocardial perfusion imaging in women with suspected myocardial ischemia and no obstructive coronary disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study.

OBJECTIVES: The purpose of this study was to assess the prognostic value of global magnetic resonance (MR) myocardial perfusion imaging (MPI) in women with suspected myocardial ischemia and no obstructive (stenosis <50%) coronary artery disease (CAD). BACKGROUND: The prognostic value of global MR-MPI in women without obstructive CAD remains unknown. METHODS: Women (n = 100, mean age 57 ± 11 years, age range 31 to 76 years), with symptoms of myocardial ischemia and with no obstructive CAD, as assessed by coronary angiography, underwent MR-MPI and standard functional assessment. During follow-up (34 ± 16 months), time to first adverse event (death, myocardial infarction, or hospitalization for worsening anginal symptoms) was analyzed using global MPI and left ventricular ejection fraction (EF) data. RESULTS: Adverse events occurred in 23 (23%) women. Using univariable Cox proportional hazards regression modeling, variables found to be predictive of adverse events were global MR-MPI average uptake slope (p < 0.05), the ratio of MR-MPI peak signal amplitude to uptake slope (p < 0.05), and EF (p < 0.05). Two multivariable Cox models were formed, 1 using variables that were performance site dependent: ratio of MR-MPI peak amplitude to uptake slope together with EF (chi square: 13, p < 0.005); and a model using variables that were performance site independent: MR-MPI slope and EF (chi square: 12, p < 0.005). Each of the 2 multivariable models remained predictive of adverse events after adjustment for age, disease history, and Framingham risk score. For each of the Cox models, patients were categorized as high risk if they were in the upper quartile of the model and as not high risk otherwise. Kaplan-Meier analysis of time to event was performed for high risk versus not high risk for site-dependent (log rank: 15.2, p < 0.001) and site-independent (log rank: 13.0, p < 001) models. CONCLUSIONS: Among women with suspected myocardial ischemia and no obstructive CAD, MR-MPI-determined global measurements of normalized uptake slope and peak signal uptake, together with global functional assessment of EF, appear to predict prognosis.

Numerical and experimental study of a novel phase contrast magnetic resonance (PC-MR) imaging technique: sparse interleaved referencing PC-MR imaging.

PURPOSE: To use numerical simulation and experimental approaches to introduce a novel phase contrast magnetic resonance (PC-MR) data processing technique termed Sparse Interleaved Referencing PC-MR, with potential to improve accuracy, temporal resolution, and signal-to-noise ratio (SNR) of PC-MR data. MATERIALS AND METHODS: Computational fluid dynamics data were generated for a two-chamber orifice flow model simulating valvular regurgitation. The numerical results were validated and used to simulate conventional and Sparse Interleaved Referencing PC-MR data acquisitions. Common data sets were processed using conventional and Sparse Interleaved Referencing approaches and quantitative errors in velocity-time waveforms were measured and compared. In vitro phantom jet flow data and in vivo ascending aorta data were acquired and used to simulate Sparse Interleaved Referencing PC-MR. RESULTS: The Sparse Interleaved Referencing PC-MR data showed significantly better representation of the velocity-time waveform in three areas: (i) lower root-mean-square errors (9.0 +/- 1.0% versus 24.0 +/- 0.2%; P < 0.005), (ii) simulation of conventionally processed data showed a pattern of peak velocity overestimation, which was experimentally demonstrated in in vitro data, whereas overestimation of peak velocity was dramatically attenuated using Sparse Interleaved Referencing (2.8 +/- 0.4% versus 16.9 +/- 6.4%, P < 0.005), and (iii) compared with the conventional scan, an average of 119.4 +/- 26.6% (P < 0.005) SNR was realized in in vitro and in vivo Sparse Interleaved Referencing PC-MR data. CONCLUSION: Simulation and in vitro/in vivo results show that Sparse Interleaved Referencing PC-MR processed data in pulsatile and jet flow showed higher accuracy, better peak velocity representation, and improved SNR compared with the data processed using the conventional PC-MR method.

A spheroidal control volume for the quantitative measurement of regurgitant flow by cardiac MRI.

PURPOSE: We sought to show that a spheroidally shaped control volume (CV), formed from a minimal MRI data set, can be used to measure regurgitant flow through a defective cardiac valve consistently and accurately under a variety of flow conditions. MATERIALS AND METHODS: Using a pulsatile flow pump and phantoms simulating severe valvular regurgitation, we acquired 31 scans of two or three radially oriented slices, using a variety of flow waveforms and regurgitant volumes of 12 to 55 ml. Data sets included high- and low-resolution scans, and variable-rate sparse sampling was also applied to reduce the scan time. An oblate spheroid was placed in the pump chamber opposite the jet and fit as tightly as possible to isomagnitude velocity contours at 25% of the velocity encoding limit. RESULTS: Normalized regurgitant volumes (NRVs) expressed as a percentage of the pump setting were obtained from the product of the spheroid surface area with the velocities normal to it. Mean +/- SD NRV values were 96.8 +/- 6.6% for all scans. Imaging times in the breath-hold range were obtained using reduced resolution and variable-rate sparse sampling approaches without significant degradation in accuracy. CONCLUSION: In our preliminary findings, the spheroidal CV method showed clear potential for the development of a robust, clinically feasible technique for the measurement of regurgitant volume.