Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m2, LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m2, and LV mass index of 41 to 76 and 33 to 57 g/m2. For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m2, LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m2, and LV mass index of 50 to 83 and 38 to 65 g/m2. For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m2, RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m2, and RV mass index of 14 to 29 and 13 to 25 g/m2. CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.

Association Between Granulocyte Colony-Stimulating Factor (G-CSF) Use and Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Among Elderly Patients with Breast, Lung, or Prostate Cancer.

INTRODUCTION: Patients diagnosed with cancer have an increased risk both for myelodysplastic syndromes (MDS) and for acute myeloid leukemia (AML) following treatment. METHODS: Using SEER-Medicare data, we selected patients aged 66 years and older who completed systemic therapy between 2002 and 2014 for breast (stage I-III), lung (stage I-III), or prostate (stage I-IV) cancer. For each cancer, we estimated the risk of a composite endpoint of MDS or AML in patients receiving granulocyte colony-stimulating factor (G-CSF) vs. not. RESULTS: The 10-year cumulative risk difference (granulocyte colony-stimulating factor [G-CSF] - no G-CSF) for MDS-AML was 0.45% (95% CI 0.13-0.77%) in breast cancer and 0.39% (95% CI 0.15-0.62%) in lung cancer. G-CSF use was associated with a hazard ratio of 1.60 (95% CI 1.07-2.40) in breast cancer and 1.50 (95% CI 0.99-2.29) in lung cancer. Filgrastim use was associated with a hazard ratio of 1.01 (95% CI 1.00-1.03) per administration in breast cancer and 1.02 (95% CI 0.99-1.05) per administration in lung cancer. Pegfilgrastim was associated with a hazard ratio of 1.08 (95% CI 1.01-1.15) per administration in breast cancer and 1.12 (95% CI 1.00-1.25) per administration in lung cancer. Analyses in prostate cancer were limited because of the low number of events. CONCLUSIONS: The use of G-CSF in patients diagnosed with breast and lung cancer is associated with an increased risk of MDS-AML. However, the MDS-AML absolute risk difference is very low.

The incidence of thrombocytopenia in adult patients receiving chemotherapy for solid tumors or hematologic malignancies.

OBJECTIVES: To estimate the risk of thrombocytopenia in various cancers and chemotherapy regimens. METHODS: Structured patient-level data from the Flatiron Health Electronic Health Record database were used to identify adult patients who received chemotherapy for a solid tumor or hematologic malignancy from 2012 to 2017. Three-month cumulative incidence of thrombocytopenia was assessed based on platelet counts, overall and by grade of thrombocytopenia. Co-occurrence of anemia, neutropenia, and leukopenia was evaluated. RESULTS: Of 15,521 patients with solid tumors, 13% had thrombocytopenia within 3 months (platelet count < 100 × 109 /L); 4% had grade 3 (25 to < 50 × 109 /L), and 2% grade 4 (<25 × 109 /L) thrombocytopenia. Of 2537 patients with hematologic malignancies, 28% had any thrombocytopenia, 16% with grade 3, and 12% with grade 4. Among patients with thrombocytopenia, it occurred without another cytopenia in 18% of solid tumors and 7% of hematologic malignancies. CONCLUSIONS: In a large, US-representative sample of patients undergoing chemotherapy in clinical practice, thrombocytopenia incidence varied across tumor and regimen types. Despite recommendations to alter chemotherapy to avoid severe thrombocytopenia, 4% of patients with solid tumors and 16% with hematologic malignancies experienced grade 3 thrombocytopenia. Prediction and prevention of thrombocytopenia may help oncologists avoid dose modifications and their adverse effects on survival.

Occurrence and Management of Thrombocytopenia in Metastatic Colorectal Cancer Patients Receiving Chemotherapy: Secondary Analysis of Data From Prospective Clinical Trials.

INTRODUCTION: Chemotherapy-induced thrombocytopenia (CIT) contributes to treatment dose delay and/or modification, often resulting in poorer survival and disease progression. We explored the incidence and clinical consequences of CIT among metastatic colorectal cancer (mCRC) patients. MATERIALS AND METHODS: Data from two prospective randomized phase 3 trials of mCRC patients receiving either first-line FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) or second-line FOLFIRI (fluorouracil, leucovorin, irinotecan) were analyzed. Thrombocytopenia was defined by platelet count < 100 × 109/L (further categorized by grade) and by recorded adverse events (AEs). Co-occurrence of anemia (hemoglobin < 12 g/dL) and neutropenia (neutrophil count < 2 × 109/L) and clinical consequences of CIT were also evaluated. RESULTS: Among 1078 mCRC patients in the FOLFOX4 study, cumulative incidence of CIT based on platelet count was 37% (grade 3, 2%; grade 4, 1%) during an average 8 months' follow-up. Neutropenia or anemia were absent in 44% of CIT episodes; 62% of CIT AEs led to chemotherapy dose delay, change, and/or discontinuation. Among 1067 mCRC patients in the FOLFIRI study, cumulative incidence of CIT based on platelet count was 4% (grade 3, < 1%; grade 4, 0) during an average 4 months' follow-up. Neutropenia or anemia were absent in 22% of CIT episodes; 32% of CIT AEs led to chemotherapy dose delay, change, and/or discontinuation. With both regimens, transfusions and hospitalizations after CIT AEs were rare (< 3%). CONCLUSION: CIT was common among mCRC patients receiving the FOLFOX4 regimen. The most frequent consequence of CIT was a delay in chemotherapy, highlighting the unmet need in CIT management.

Magnetic resonance multitasking for multidimensional assessment of cardiovascular system: Development and feasibility study on the thoracic aorta.

PURPOSE: To develop an MR multitasking-based multidimensional assessment of cardiovascular system (MT-MACS) with electrocardiography-free and navigator-free data acquisition for a comprehensive evaluation of thoracic aortic diseases. METHODS: The MT-MACS technique adopts a low-rank tensor image model with a cardiac time dimension for phase-resolved cine imaging and a T2 -prepared inversion-recovery dimension for multicontrast assessment. Twelve healthy subjects and 2 patients with thoracic aortic diseases were recruited for the study at 3 T, and both qualitative (image quality score) and quantitative (contrast-to-noise ratio between lumen and wall, lumen and wall area, and aortic strain index) analyses were performed in all healthy subjects. The overall image quality was scored based on a 4-point scale: 3, excellent; 2, good; 1, fair; and 0, poor. Statistical analysis was used to test the measurement agreement between MT-MACS and its corresponding 2D references. RESULTS: The MT-MACS images reconstructed from acquisitions as short as 6 minutes demonstrated good or excellent image quality for bright-blood (2.58 ± 0.46), dark-blood (2.58 ± 0.50), and gray-blood (2.17 ± 0.53) contrast weightings, respectively. The contrast-to-noise ratios for the three weightings were 49.2 ± 12.8, 20.0 ± 5.8 and 2.8 ± 1.8, respectively. There were good agreements in the lumen and wall area (intraclass correlation coefficient = 0.993, P < .001 for lumen; intraclass correlation coefficient = 0.969, P < .001 for wall area) and strain (intraclass correlation coefficient = 0.947, P < .001) between MT-MACS and conventional 2D sequences. CONCLUSION: The MT-MACS technique provides high-quality, multidimensional images for a comprehensive assessment of the thoracic aorta. Technical feasibility was demonstrated in healthy subjects and patients with thoracic aortic diseases. Further clinical validation is warranted.

Clinical audiometric patterns of hearing loss following blast-related injury in U.S. military personnel.

Objective: To identify clinical audiometric patterns of hearing loss following blast-related injury (BRI) in US military personnel.Design: Retrospective cohort study.Study sample: A total of 1186 male Navy and Marine Corps service members with normal hearing thresholds on pre-injury audiograms who had post-injury audiograms in the Blast-Related Auditory Injury Database.Results: Low- and high-frequency pure-tone averages (PTAs) were significantly higher in those with BRI than non-blast-related injury (NBRI) for both ears (p < 0.001 for all comparisons). Overall, 172 (15%) service members met criteria for post-injury hearing loss and were categorised into PTA or single-frequency hearing loss subgroups. PTA hearing loss was more common in the BRI group (50% vs. 33%, p < 0.036), whereas single-frequency hearing loss was more common in the NBRI group. Most hearing loss was mild to moderate in degree, and three distinct audiometric patterns emerged (i.e. flat, sloping and rising). A flat pattern was the most prevalent configuration among those with PTA hearing loss, especially bilateral loss. Single-frequency hearing loss was mostly unilateral and high frequency.Conclusions: In this study, BRI produced hearing loss across test frequencies, generating more clinically actionable post-injury audiograms than NBRI. We found that post-injury audiometric patterns of hearing loss among military personnel may vary.

The incidence and clinical burden of immune thrombocytopenia in pediatric patients in the United States.

Immune thrombocytopenia (ITP) is the most common bleeding disorder diagnosed in children. Characterized by low platelet counts, it leads to reduced clotting abilities and an increased tendency to bleed. The disorder in children is often self-limiting. However, approximately 25% of children develop persistent or chronic ITP, and bleeding associated with thrombocytopenia can be life-threatening. The current incidence of ITP in the US and the characterization of the illness among children being managed in routine clinical practice are sparsely reported. This retrospective cohort study leveraged a large US-based commercial claims database to estimate the current incidence of pediatric ITP, the uptake of ITP treatments, and the occurrence of clinical outcomes of interest. Overall, the incidence of ITP in patients <18 years was 8.8 (95% confidence interval; 8.5-9.1) per 100,000 person-years from 2011 to 2016. Within two years of ITP onset, >31% of patients received IVIg and/or oral corticosteroids. Other ITP therapies were less common. During this same time period, 50% had at least one bleeding event (ecchymosis, epistaxis, gastrointestinal hemorrhage, etc.), 24% were hospitalized for a bleeding event, and 62% had at least one ITP-related hospitalization. The majority of patients experiencing these events did so within the first month following ITP onset. Our findings confirm the rarity of ITP and relatively low likelihood of chronic disease in young patients, but reveal that for a significant proportion of patients in the newly diagnosed phase, clinical consequences can be serious. Further study of improved treatment methods throughout the disease course is warranted.

Deep learning within a priori temporal feature spaces for large-scale dynamic MR image reconstruction: Application to 5-D cardiac MR Multitasking.

High spatiotemporal resolution dynamic magnetic resonance imaging (MRI) is a powerful clinical tool for imaging moving structures as well as to reveal and quantify other physical and physiological dynamics. The low speed of MRI necessitates acceleration methods such as deep learning reconstruction from under-sampled data. However, the massive size of many dynamic MRI problems prevents deep learning networks from directly exploiting global temporal relationships. In this work, we show that by applying deep neural networks inside a priori calculated temporal feature spaces, we enable deep learning reconstruction with global temporal modeling even for image sequences with >40,000 frames. One proposed variation of our approach using dilated multi-level Densely Connected Network (mDCN) speeds up feature space coordinate calculation by 3000x compared to conventional iterative methods, from 20 minutes to 0.39 seconds. Thus, the combination of low-rank tensor and deep learning models not only makes large-scale dynamic MRI feasible but also practical for routine clinical application.

Temporal trends in treatment and survival of older adult diffuse large B-Cell lymphoma patients in the SEER-Medicare linked database.

To describe temporal trends in treatment among older adult (≥66 years) patients diagnosed with diffuse large B-cell lymphoma (DLBCL), we analyzed 18,058 DLBCL patients from the Surveillance, Epidemiology, and End Results linked Medicare (SEER-Medicare) database diagnosed between 2001 and 2013. Among 65% of patients receiving treatment after diagnosis, R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) was the most common frontline therapy, increasing with more recent treatment year: 51% (2001-2003) vs. 69% (2010-2014). Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) was uncommon in these Medicare patients. As the addition of rituximab increased over time, we also observed an improved survival rate over time. It is possible there is an association, but we cannot make this inference as effectiveness was not measured in this study. Overall survival estimates indicated that survival probabilities steadily improved in more recent years; however, 5-year survival was <40%, indicating the need for improved treatment options for older adult DLBCL patients.

Free-breathing, non-ECG, continuous myocardial T1 mapping with cardiovascular magnetic resonance multitasking.

PURPOSE: To evaluate the accuracy and repeatability of a free-breathing, non-electrocardiogram (ECG), continuous myocardial T1 and extracellular volume (ECV) mapping technique adapted from the Multitasking framework. METHODS: The Multitasking framework is adapted to quantify both myocardial native T1 and ECV with a free-breathing, non-ECG, continuous acquisition T1 mapping method. We acquire interleaved high-spatial resolution image data and high-temporal resolution auxiliary data following inversion-recovery pulses at set intervals and perform low-rank tensor imaging to reconstruct images at 344 inversion times, 20 cardiac phases, and 6 respiratory phases. The accuracy and repeatability of Multitasking T1 mapping in generating native T1 and ECV maps are compared with conventional techniques in a phantom, a simulation, 12 healthy subjects, and 10 acute myocardial infarction patients. RESULTS: In phantoms, Multitasking T1 mapping correlated strongly with the gold-standard spin-echo inversion recovery (R2 = 0.99). A simulation study demonstrated that Multitasking T1 mapping has similar myocardial sharpness to the fully sampled ground truth. In vivo native T1 and ECV values from Multitasking T1 mapping agree well with conventional MOLLI values and show good repeatability for native T1 and ECV mapping for 60 seconds, 30 seconds, or 15 seconds of data. Multitasking native T1 and ECV in myocardial infarction patients correlate positively with values from MOLLI. CONCLUSION: Multitasking T1 mapping can quantify native T1 and ECV in the myocardium with free-breathing, non-ECG, continuous scans with good image quality and good repeatability in vivo in healthy subjects, and correlation with MOLLI T1 and ECV in acute myocardial infarction patients.

Magnetic resonance multitasking for motion-resolved quantitative cardiovascular imaging.

Quantitative cardiovascular magnetic resonance (CMR) imaging can be used to characterize fibrosis, oedema, ischaemia, inflammation and other disease conditions. However, the need to reduce artefacts arising from body motion through a combination of electrocardiography (ECG) control, respiration control, and contrast-weighting selection makes CMR exams lengthy. Here, we show that physiological motions and other dynamic processes can be conceptualized as multiple time dimensions that can be resolved via low-rank tensor imaging, allowing for motion-resolved quantitative imaging with up to four time dimensions. This continuous-acquisition approach, which we name cardiovascular MR multitasking, captures - rather than avoids - motion, relaxation and other dynamics to efficiently perform quantitative CMR without the use of ECG triggering or breath holds. We demonstrate that CMR multitasking allows for T1 mapping, T1-T2 mapping and time-resolved T1 mapping of myocardial perfusion without ECG information and/or in free-breathing conditions. CMR multitasking may provide a foundation for the development of setup-free CMR imaging for the quantitative evaluation of cardiovascular health.

Inverse association of MRI-derived native myocardial T1 and perfusion reserve index in women with evidence of ischemia and no obstructive CAD: A pilot study.

BACKGROUND: It has recently been shown that magnetic resonance (MR) "native T1" mapping is capable of characterizing abnormal microcirculation in patients with obstructive coronary artery disease (CAD). In studies involving women with signs and symptoms of ischemia and no obstructive CAD (INOCA), however, the potential role of native T1 as an imaging marker and its association with indices of diastolic function or vasodilator-induced myocardial ischemia have not been explored. We investigated whether native T1 in INOCA is associated with reduced myocardial perfusion reserve index (MPRI) or with diastolic dysfunction. METHODS: Twenty-two female patients with INOCA and twelve female reference controls with matching age and body-mass index were studied. The patients had evidence of vasodilator-induced ischemia without obstructive CAD or any prior infarction. All 34 subjects underwent stress/rest MR including native T1 mapping (MOLLI 5(3)3) at 1.5-Tesla. RESULTS: Compared with controls, patients had similar morphology/function. As expected, MPRI was significantly reduced in patients compared to controls (1.78 ±â€¯0.39 vs. 2.49 ±â€¯0.41, p < 0.0001). Native T1 was significantly elevated in patients (1040.1 ±â€¯29.3 ms vs. 1003.8 ±â€¯18.5 ms, p < 0.001) and the increased T1 showed a significant inverse correlation with MPRI (r = -0.481, p = 0.004), but was not correlated with reduced diastolic strain rate. CONCLUSIONS: Symptomatic women with INOCA have elevated native T1 compared to matched reference controls and there is a significant association between elevated native T1 and impaired MPRI, considered a surrogate measure of ischemia severity in this cohort. Future studies in a larger cohort are needed to elucidate the mechanism underlying this inverse relationship.

Chemical exchange saturation transfer fingerprinting for exchange rate quantification.

PURPOSE: There is an increased interest to determine the exchange rate using CEST to provide pH information. However, current CEST quantification methods require lengthy scan times and do not address magnetization transfer effects. The purpose of this work was to apply the magnetic resonance fingerprinting (MRF) concept to CEST to achieve more efficient and accurate exchange rate quantification. METHODS: The proposed CEST fingerprinting method used varying saturation powers and saturation times to create unique signal evolutions for different exchange rates. The acquired signal was matched to a predefined dictionary to determine the exchange rate. The magnetization transfer effects were also addressed in the framework of CEST fingerprinting: The simulated dictionary could predict the signal curves without magnetization transfer effects, and comparing the dictionary to the acquired signals allowed the correction of the magnetization transfer effects. The CEST fingerprinting method was compared with the conventional pulsed quantitative CEST method using omega plots in the creatine phantom study. RESULTS: The CEST fingerprinting method has a significantly reduced scan time (10 minutes versus 50 minutes) while providing more accurate exchange rate quantification using literature values as the reference. CONCLUSION: In this study, we demonstrate that CEST fingerprinting is more efficient (5 times faster) compared with pulsed quantitative CEST. It is also shown that the results of the proposed CEST fingerprinting technique are much closer to the literature values than pulsed quantitative CEST at 3 T.

Impact of Blast Injury on Hearing in a Screened Male Military Population.

Exposure to hazardous intensity levels of combat noise, such as blast, may compromise a person's ability to detect and recognize sounds and communicate effectively. There is little previous examination of the onset of hearing health outcomes following exposure to blast in representative samples of deployed US military personnel. Data from the prospective Blast-Related Auditory Injury Database were analyzed. We included only those participants with qualified hearing tests within a period of 12 months prior to, and following, injury (n = 1,574). After adjustment for relevant covariates and potential confounders, those who sustained a blast injury had significantly higher odds of postinjury hearing loss (odds ratio = 2.21; 95% confidence interval: 1.42, 3.44), low-frequency hearing loss (odds ratio = 1.95; 95% confidence interval: 1.01, 3.78), high-frequency hearing loss (odds ratio = 2.45; 95% confidence interval: 1.43, 4.20), and significant threshold shift compared with a group with non-blast-related injury. An estimated 49% of risk for hearing loss in these blast-injured, deployed military members could be attributed to the blast-related injury event. This study reinforced that it is imperative to identify at-risk populations for early intervention and prevention, as well as to consistently monitor the effects of blast injury on hearing outcomes.

Optimized CEST cardiovascular magnetic resonance for assessment of metabolic activity in the heart.

BACKGROUND: Previous studies have linked cardiac dysfunction to loss of metabolites in the creatine kinase system. Chemical exchange saturation transfer (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging technique and has been applied in the heart for creatine mapping. However, current limitations include: (a) long scan time, (b) residual cardiac and respiratory motion, and (c) B0 field variations induced by respiratory motion. An improved CEST CMR technique was developed to address these problems. METHODS: Animals with chronic myocardial infarction (N = 15) were scanned using the proposed CEST CMR technique and a late gadolinium enhancement (LGE)  sequence as reference. The major improvements of the CEST CMR technique are: (a) Images were acquired by single-shot FLASH, significantly increasing the scan efficiency. (b) All images were registered to reduce the residual motion. (c) The acquired Z-spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST signal, reducing the impact of B0 field shifting due to respiratory motion. Feasibility of the technique was tested in a porcine model with chronic myocardial infarction. CEST signal was measured in the scar, border zone and remote myocardium. Initial studies were performed in one patient. RESULTS: In all animals, healthy remote myocardial CEST signal was elevated (0.16 ± 0.02) compared to infarct CEST signal (0.09 ± 0.02, P < 0.001) and the border zone (0.12 ± 0.02, P < 0.001). For both animal and patient studies, the hypointense regions in the CEST contrast maps closely match the bright areas in the LGE images. CONCLUSIONS: The proposed CEST CMR technique was developed to address long scan times, respiratory and cardiac motion, and B0 field variations. Lower CEST signal in bright region of the LGE image is consistent with the fact that myocardial infarction has reduced metabolic activity.

Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with ranolazine.

BACKGROUND: Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine-a late sodium current inhibitor-improves diastolic function in animal models and subjects with obstructive coronary artery disease (CAD). HYPOTHESIS: We hypothesized that ranolazine would beneficially alter diastolic function in CMD. METHODS: To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD and from 43 healthy reference controls. RESULTS: Diastolic strain rate was impaired in CMD vs controls (circumferential diastolic strain rate: 99.9% ± 2.5%/s vs 120.1% ± 4.0%/s, P = 0.0003; radial diastolic strain rate: -199.5% ± 5.5%/s vs -243.1% ± 9.6%/s, P = 0.0008, case vs control). Moreover, peak systolic circumferential strain (CS) and radial strain (RS) were also impaired in cases vs controls (CS: -18.8% ± 0.3% vs -20.7% ± 0.3%; RS: 35.8% ± 0.7% vs 41.4% ± 0.9%; respectively; both P < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis, however, we observed no significant changes in left ventricular diastolic function in CMD cases after 2 weeks of ranolazine vs placebo. CONCLUSIONS: The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have subclinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD.

Guideline Adherence for Echocardiographic Follow-Up in Outpatients with at Least Moderate Valvular Disease.

BACKGROUND: Attention to resource utilization has led to increased scrutiny of the appropriateness of initial diagnostic imaging studies on the basis of current guidelines. Far less attention has been paid to examining the lack of appropriate follow-up studies. METHODS: A retrospective cross-sectional analysis was performed of 3,781 consecutive outpatients referred for transthoracic echocardiography (TTE) from July to December 2008. Data from the electronic medical records were extracted to see if patients with at least moderate left-sided valvular stenosis or regurgitation underwent subsequent echocardiographic studies within 60 days of the period recommended by the 2006 American College of Cardiology and American Heart Association valve guidelines document. RESULTS: Of 342 outpatients with at least moderate valve dysfunction, 38 (11%) were excluded for reasons that precluded the need for a follow-up study (e.g. death, surgery). Of the remaining 304 patients, only 179 (59%) underwent follow-up echocardiography within the recommended period. Rates of timely follow-up TTE were higher when ordering physicians were cardiologists or cardiovascular surgeons (65%) compared with primary care physicians or internal medicine specialists (45%) (P < .01). Follow-up rates were significantly different for aortic stenosis (77%), mitral stenosis (67%), aortic regurgitation (49%), and mitral regurgitation (49%) (P < .01). Patients receiving timely follow-up TTE were younger (66 ± 15 vs 71 ± 15 years, P = .002) and more likely to be male (odds ratio, 1.79; 95% CI, 1.12-2.85; P = .01). CONCLUSIONS: To the authors' knowledge, this is the first study demonstrating low rates of compliance with guideline-recommended monitoring TTE in patients with at least moderate valve dysfunction. Cardiac practitioners have significantly better compliance. Strategies are needed to improve timely follow-up care in this population.

Left atrial late gadolinium enhancement with water-fat separation: the importance of phase-encoding order.

PURPOSE: To compare two late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) methods: a Dixon LGE sequence with sequential phase-encoding order, reconstructed using water-fat separation, and standard fat-saturated LGE. MATERIALS AND METHODS: We implemented a dual-echo Dixon LGE method for reconstructing water-only images and compared it to fat-saturated LGE in 12 patients prior to their first pulmonary vein isolation (PVI) procedure. Images were analyzed for quality and fat-suppression. Regions of the left atrium were evaluated by a blinded observer (1 = prominent enhancement, 0 = mild or absent enhancement) on two sets of images (fat-saturated and water-only LGE) and agreement was assessed. RESULTS: Water-only LGE showed a trend toward better fat-suppression (P = 0.06), with a significantly more homogeneous blood pool signal and reduced inflow artifacts (both P < 0.01). Agreement between fat-saturated LGE and water-only methods was found in 84% of regions, significantly correlated by chi-squared test (P < 0.001). The kappa value was 0.52 (moderate). The average number of enhancing segments was higher for fat-saturated LGE than water-only LGE (4.2 ± 2.7 vs. 3.2 ± 2.9, P = 0.03). CONCLUSION: The two-point Dixon LGE technique reduces artifacts due to a centric k-space order. A similar enhancement pattern was observed irrespective of the LGE technique, with more enhancement detected by fat-saturated LGE.

Scar heterogeneity on cardiovascular magnetic resonance as a predictor of appropriate implantable cardioverter defibrillator therapy.

BACKGROUND: Despite the survival benefit of implantable-cardioverter-defibrillators (ICDs), the vast majority of patients receiving an ICD for primary prevention do not receive ICD therapy. We sought to assess the role of heterogeneous scar area (HSA) identified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) in predicting appropriate ICD therapy for primary prevention of sudden cardiac death (SCD). METHODS: From September 2003 to March 2011, all patients who underwent primary prevention ICD implantation and had a pre-implantation LGE-CMR were identified. Scar size was determined using thresholds of 4 and 6 standard deviations (SD) above remote normal myocardium; HSA was defined using 3 different criteria; as the region between 2 SD and 4 SD (HSA2-4SD), between 2SD and 6SD (HSA2-6SD), and between 4SD and 6SD (HSA4-6SD). The end-point was appropriate ICD therapy. RESULTS: Out of 40 total patients followed for 25 ± 24 months, 7 had appropriate ICD therapy. Scar size measured by different thresholds was similar in ICD therapy and non-ICD therapy groups (P = NS for all). However, HSA2-4SD and HSA4-6SD were significantly larger in the ICD therapy group (P = 0.001 and P = 0.03, respectively). In multivariable model HSA2-4SD was the only significant independent predictor of ICD therapy (HR = 1.08, 95%CI: 1.00-1.16, P = 0.04). Kaplan-Meier analysis showed that patients with greater HSA2-4SD had a lower survival free of appropriate ICD therapy (P = 0.026). CONCLUSIONS: In primary prevention ICD implantation, LGE-CMR HSA identifies patients with appropriate ICD therapy. If confirmed in larger series, HSA can be used for risk stratification in primary prevention of SCD.

Volumetric left ventricular ejection fraction is superior to 2-dimensional echocardiography for risk stratification of patients for primary prevention implantable cardioverter-defibrillator implantation.

Current guidelines recommend an implantable cardioverter-defibrillator (ICD) according to the left ventricular ejection fraction (LVEF). However, they do not mandate volumetric LVEF assessment. We sought to determine whether volumetric LVEF measurement using cardiovascular magnetic resonance imaging (CMR-LVEF) is superior to conventional LVEF measurement using 2-dimensional transthoracic echocardiography (Echo-LVEF) for risk stratifying patients referred for primary prevention ICD. Patients who underwent primary prevention ICD implantation at our institution and had undergone preimplantation CMR-LVEF from November 2001 to February 2011 were identified. Volumetric CMR-LVEF was determined from cine short-axis data sets. CMR-LVEF and Echo-LVEF were extracted from the clinical reports. The end point was appropriate ICD discharge (shock and/or antitachycardia pacing). Of 48 patients, appropriate ICD discharge occurred in 9 (19%) within 29 ± 25 months (range 1 to 99, median 20). All patients met the Echo-LVEF criteria for ICD implantation; however 25% (95% confidence interval 13% to 37%) did not meet the CMR-LVEF criteria. None (0%) of these latter patients had received an appropriate ICD discharge. Using CMR-LVEF ≤30% as a threshold for ICD eligibility, 19 patients (40%) with a qualifying Echo-LVEF would not have been referred for ICD, and none (0%) received an ICD discharge.For primary prevention ICD implantation, volumetric CMR-LVEF might be superior to clinical Echo-LVEF for risk stratification and can identify a large minority of subjects in whom ICD implantation can be safely avoided. In conclusion, if confirmed by larger prospective series, volumetric methods such as CMR should be considered a superior "gatekeeper" for the identification of patients likely to benefit from primary prevention ICD implantation.