Craig Butler

Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review

BackgroundScreening for organ rejection is a critical component of care for patients who have undergone heart transplantation. Endomyocardial biopsy is the gold standard screening tool, but non-invasive alternatives are needed. Cardiovascular magnetic resonance (CMR) is well suited to provide an alternative to biopsy because of its ability to quantify ventricular function, morphology, and characterize myocardial tissue. CMR is not widely used to screen for heart transplant rejection, despite many trials supporting its use for this indication. This review summarizes the different CMR sequences that can detect heart transplant rejection as well as the strengths and weaknesses of their application.ResultsT2 quantification by spin echo techniques has been criticized for poor reproducibility, but multiple studies show its utility in screening for rejection. Human and animal data estimate that T2 quantification can diagnose rejection with sensitivities and specificities near 90%. There is also a suggestion that T2 quantification can predict rejection episodes in patients with normal endomyocardial biopsies.T1 quantification has also shown association with biopsy proven rejection in a small number of trials. T1 weighted gadolinium early enhancement appeared promising in animal data, but has had conflicting results in human trials. Late gadolinium enhancement in the diagnosis of rejection has not been evaluated.CMR derived measures of ventricular morphology and systolic function have insufficient sensitivity to diagnose mild to moderate rejection. CMR derived diastolic function can demonstrate abnormalities in allografts compared to native human hearts, but its ability to diagnose rejection has not yet been tested.There is promising animal data on the ability of iron oxide contrast agents to illustrate the changes in vascular permeability and macrophage accumulation seen in rejection. Despite good safety data, these contrast agents have not been tested in the human heart transplant population.ConclusionT2 quantification has demonstrated the best correlation to biopsy proven heart transplant rejection. Further studies evaluating diastolic function, late gadolinium enhancement, and iron oxide contrast agents to diagnose rejection are needed. Future studies should focus on combining multiple CMR measures into a transplant rejection scoring system which would improve sensitivity and possibly reduce, if not eliminate, the need for endomyocardial biopsy.

Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection.

BACKGROUND Endomyocardial biopsy (EMB) is the current gold standard to screen for heart transplant rejection but has important risks and limitations. Cardiovascular magnetic resonance imaging (CMRI) is increasingly used to characterize cardiac function and myocardial tissue. We evaluated the diagnostic accuracy of CMRI compared with EMB and clinically diagnosed heart transplant rejection. METHODS Comprehensive CMRI scans were performed on adult heart transplant recipients within 24 hours of EMB (routine or clinically indicated), before initiation of any anti-rejection therapy, and blinded to EMB results. Multivariable analysis was used to create CMRI diagnostic criteria for comparison with a positive EMB (Grade ≥ 2R or antibody-mediated rejection) and clinical rejection (change in medical therapy to treat rejection). RESULTS Sixty participants (75% male; mean age, 51 ± 14 years) were recruited, providing 73 comparisons between CMRI and EMB for the diagnosis of rejection. Multivariable logistic regression identified myocardial edema (T2 relaxation time) and right ventricular end-diastolic volume index as independent predictors of a positive EMB. Combining threshold right ventricular end-diastolic volume index and edema values predicted a positive EMB with very good accuracy: sensitivity, 93%; specificity, 78%; positive predictive value, 52%; and negative predictive valve, 98%. CMRI was more sensitive than EMB at predicting clinical rejection (sensitivity of 67% vs 58%). CONCLUSIONS CMRI has high sensitivity and high negative predictive value in predicting biopsy-positive heart transplant rejection and may be useful as a screening test before routine EMB. CMRI also has better sensitivity for clinically diagnosed heart transplant rejection and could be helpful in cases of negative rejection on the biopsy specimen.

Prognostic capabilities of coronary computed tomographic angiography before non-cardiac surgery: Prospective cohort study

Objectives To determine if coronary computed tomographic angiography enhances prediction of perioperative risk in patients before non-cardiac surgery and to assess the preoperative coronary anatomy in patients who experience a myocardial infarction after non-cardiac surgery. Design Prospective cohort study. Setting 12 centers in eight countries. Participants 955 patients with, or at risk of, atherosclerotic disease who underwent non-cardiac surgery. Interventions Coronary computed tomographic angiography was performed preoperatively; clinicians were blinded to the results unless left main disease was suspected. Results were classified as normal, non-obstructive (<50% stenosis), obstructive (one or two vessels with ≥50% stenosis), or extensive obstructive (≥50% stenosis in two vessels including the proximal left anterior descending artery, three vessels, or left main). Main outcome measure Composite of cardiovascular death and non-fatal myocardial infarction within 30 days after surgery (primary outcome). This was the dependent variable in Cox regression. The independent variables were scores on the revised cardiac risk index and findings on coronary computed tomographic angiography. Results The primary outcome occurred in 74 patients (8%). The model that included both scores on the revised cardiac risk index and findings on coronary computed tomographic angiography showed that coronary computed tomographic angiography provided independent prognostic information (P=0.014; C index=0.66). The adjusted hazard ratios were 1.51 (95% confidence interval 0.45 to 5.10) for non-obstructive disease; 2.05 (0.62 to 6.74) for obstructive disease; and 3.76 (1.12 to 12.62) for extensive obstructive disease. For the model with coronary computed tomographic angiography compared with the model based on the revised cardiac risk index alone, with 30 day risk categories of <5%, 5-15%, and >15% for the primary outcome, the results of risk reclassification indicate that in a sample of 1000 patients that coronary computed tomographic angiography would have resulted appropriately in 17 net patients receiving a higher risk estimation among the 77 patients who would have experienced the primary outcome (P<0.001). Coronary computed tomographic angiography, however, would have resulted inappropriately in 98 net patients receiving a higher risk estimation, among the 923 patients who would not have experienced the primary outcome (P<0.001). Among patients who had a perioperative myocardial infarction, preoperative coronary anatomy showed extensive obstructive disease in 31% (22/71), obstructive disease in 41% (29/71), non-obstructive disease in 24% (17/71), and normal findings in 4% (3/71). Conclusions Though findings on coronary computed tomographic angiography can improve estimation of risk for patients who will experience perioperative cardiovascular death or myocardial infarction, findings are more than five times as likely to lead to an inappropriate overestimation of risk among patients who will not experience these outcomes. Perioperative myocardial infarction occurs across the spectrum of coronary artery disease, suggesting that there could be several pathophysiologic mechanisms.

The paradox of left ventricular assist device unloading and myocardial recovery in end-stage dilated cardiomyopathy: implications for heart failure in the elderly

Dilated cardiomyopathy (DCM) is a common debilitating condition with limited therapeutic options besides heart transplantation or palliation. It is characterized by maladaptive remodeling of cardiomyocytes, extracellular collagen matrix (ECCM) and left ventricular (LV) geometry which contributes to further dysfunction. LV assist devices (LVADs) can reverse adverse remodeling in end-stage DCM. However, there is a disconnect between the benefits of prolonged unloading with LVAD at molecular and cellular levels and the low rate of bridge to recovery (BTR). Potential explanations for this paradox include insufficient reverse ECCM remodeling and/or excessive reverse cardiomyocyte remodeling with atrophy. LVAD therapy is associated with decreased collagen turnover and cross-linking and increased tissue angiotensin II (AngII), whereas LVAD combined with angiotensin-converting enzyme inhibition results in decreased tissue AngII and collagen cross-linking, normalizes LV end-diastolic pressure volume relationships and is associated with modestly higher rates of BTR. Much remains to be learned about ventricular reverse remodeling after LVAD. This can be facilitated through systematic collection and comparison of recovered and unrecovered myocardium. Importantly, vigilant monitoring for ventricular recovery among LVAD patients is needed, particularly in older patients receiving LVAD for destination therapy. In addition, prospective multicenter trials are needed to clarify the potential benefit of concomitant heart failure therapy with selective β2 agonism on ventricular recovery.

Assessment of Mitral Valve Stenosis by Helical MDCT: Comparison With Transthoracic Doppler Echocardiography and Cardiac Catheterization

OBJECTIVE We evaluated the precision of helical MDCT for the quantification of mitral valve stenosis (MVS) compared with transthoracic echocardiography (TTE) and cardiac catheterization. MATERIALS AND METHODS A total of 28 patients with MVS of differing severity underwent an ECG-gated contrast-enhanced MDCT scan. The mitral valve area (MVA) was determined planimetrically by MDCT and was compared with Doppler TTE using the pressure half-time method and with cardiac catheterization using the Gorlin formula. RESULTS Planimetry of the MVA with MDCT was feasible in all cases. The MVA on MDCT (1.88 ± 0.76 cm(2)) was significantly larger than that seen with TTE (1.74 ± 0.75 cm(2); p = 0.039) or cardiac catheterization (1.72 ± 0.67 cm(2); p = 0.037). The correlation between MDCT and TTE (r = 0.90; p < 0.001; limits of agreement, ± 0.65 cm(2)) and that between MDCT and cardiac catheterization (r = 0.86; p < 0.001; limits of agreement, ± 0.76 cm(2)) were good and similar to the correlation between TTE and cardiac catheterization (r = 0.88; p < 0.001; limits of agreement, ± 0.71 cm(2)). The best cutoff level for detecting moderate-to-severe stenosis at MDCT was an MVA of 1.70 cm(2), resulting in a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 73%, 88%, 82%, 80%, and 83%, respectively, with two false-positive and three false-negative results. CONCLUSION The MVA planimetrically determined by MDCT is systematically larger than those calculated by Doppler TTE and cardiac catheterization. However, because of a good correlation between methods and adjustment for the systematic bias, MDCT may allow reliable quantification of MVS and effectual discrimination among severity grades, although discrepancies between methods remain in individual cases.

Comparison of non-gated vs. electrocardiogram-gated 64-detector-row computed tomography for integrated electroanatomic mapping in patients undergoing pulmonary vein isolation

AIMS To compare non-gated vs. electrocardiogram (ECG)-gated 64-detector-row computed tomography (MDCT) of the left atrium (LA) for integrated electroanatomic mapping (EAM) in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS Twenty-nine consecutive patients with paroxysmal AF underwent MDCT prior to pulmonary vein isolation (PVI). All patients were in sinus rhythm both during CT imaging and PVI. Multi-detector-row computed tomography was performed in 15 patients without ECG-gating (non-gated MDCT) and in 14 patients with retrospective ECG-gating (ECG-gated MDCT). Image quality of LA reconstructions from MDCT was rated on a five-point scale (from 1 = excellent to 5 = segmentation failed). Registration error between LA geometry obtained from EAM and MDCT was calculated as the mean distance between EAM points and MDCT surface. In all patients, LA was successfully segmented from MDCT data. The segmentation process took 2:31 +/- 0:54 min for non-gated MDCT and 2:36 +/- 0:47 min for ECG-gated MDCT (P = 0.8). Image quality scores of LA reconstructions from non-gated and ECG-gated MDCT were 1.3 +/- 0.6 and 1.4 +/- 0.7, respectively (P = 0.76). There was no significant difference in the registration error between non-gated and ECG-gated MDCT (1.8 +/- 0.2 vs. 1.9 +/- 0.3 mm, respectively; P = 0.6). The radiation dose of non-gated MDCT was significantly lower compared with ECG-gated MDCT (4.6 +/- 1.4 vs. 13.4 +/- 3.6 mSv, respectively; P < 0.001). CONCLUSION Non-gated MDCT depicts LA with appropriate image quality for integrated EAM, while exposing patients to substantially lower radiation dose compared with ECG-gated MDCT.

Late Gadolinium Enhancement in Cardiac Transplant Patients Is Associated With Adverse Ventricular Functional Parameters and Clinical Outcomes

BACKGROUND Heart transplant recipients (HTRs) experience multiple cardiac complications, many of which might produce myocardial fibrosis. Cardiovascular magnetic resonance imaging (CMR) can image myocardial fibrosis using late gadolinium enhancement (LGE) imaging. We hypothesized that the presence and volume of LGE in heart transplant recipients correlates with left ventricular (LV) functional parameters and clinical outcomes. METHODS Thirty-eight stable HTRs underwent a CMR study and clinical follow-up. RESULTS In 38 stable HTRs, LGE was seen in 19 patients (50%), of which 15 (79%) had a nonischemic pattern and 4 (21%) had an ischemic pattern. LGE volume was associated with reduced LV ejection fraction (EF) (R(2) = 0.57; P = 0.001) and increased LV end-diastolic volume (R(2) = 0.59; P = 0.001). The presence of LGE was associated with cardiovascular death or hospitalization within the next year (P = 0.04), and patients who died or were hospitalized had more LGE than those that were not hospitalized (15 g vs 7 g; P = 0.03). CONCLUSIONS LGE is common in HTR and is associated with adverse ventricular remodelling and adverse clinical outcomes. LGE might be a useful noninvasive approach to monitor graft disease in asymptomatic patients after heart transplant.

Whole-heart coronary magnetic resonance angiography at 1.5 Tesla: does a blood-pool contrast agent improve diagnostic accuracy?

Objectives:To evaluate the impact of the blood-pool contrast agent gadofosveset trisodium on diagnostic accuracy of whole-heart coronary magnetic resonance angiography (CMRA) at 1.5 Tesla. Materials and Methods:Thirty consecutive patients with suspected coronary artery disease underwent free-breathing whole-heart CMRA at 1.5 Tesla. CMRA was performed with a T2-prepared steady-state free precession sequence (unenhanced CMRA) and an inversion-recovery-prepared steady-state free precession sequence after administration of gadofosveset trisodium (contrast-enhanced CMRA). Two readers independently performed a per-segment evaluation of CMRA (8 proximal and mid coronary segments) for detection of significant stenosis (≥50%) using invasive coronary angiography as reference. Disagreement was settled by consensus reading and interobserver variability was assessed using an unweighted kappa statistic. Results:Whole-heart CMRA was successfully performed in 27 patients. The percentage of assessable segments was significantly lower on unenhanced CMRA compared with contrast-enhanced CMRA (Reader 1: 79% [170/216] vs. 89% [192/216], respectively; Reader 2: 73% [157/216] vs. 87% [188/216], respectively; P < 0.001). Intention-to-diagnose analysis of the consensus reading yielded sensitivity, specificity, and diagnostic accuracy of unenhanced versus contrast-enhanced CMRA as follows: 73.1% versus 73.1% (P = 1.0), 68.3% versus 80.2% (P = 0.002), and 68.9% versus 79.3% (P = 0.004), respectively. The kappa value for interobserver agreement was 0.61 (95% confidence interval = 0.50–0.72) for unenhanced CMRA and 0.72 (95% confidence interval = 0.62–0.82) for contrast-enhanced CMRA. Conclusions:The blood-pool contrast agent gadofosveset trisodium increased the number of assessable coronary segments on whole-heart CMRA in comparison to unenhanced whole-heart CMRA. The impact of gadofosveset trisodium on diagnostic accuracy, however, was only minor.

Gadofosveset trisodium-enhanced magnetic resonance angiography of the left atrium—A feasibility study

AIM Imaging of the left atrium is regularly performed prior to pulmonary vein isolation. The aim of the study was to evaluate the feasibility of contrast-enhanced high-resolution magnetic resonance angiography (MRA) of the left atrium using the blood-pool contrast agent gadofosveset trisodium in comparison to noncontrast MRA. MATERIALS AND METHODS Twenty consecutive patients were examined by free-breathing electrocardiogram-gated whole-heart MRA (reconstructed spatial resolution, 0.7mm x 0.6mm x 0.8mm) with a noncontrast T2-prepared steady state free precession sequence (T2-prep SSFP) and a gadofosveset trisodium-enhanced inversion-recovery SSFP sequence (CE IR-SSFP). Contrast-to-noise ratio (CNR) of blood in the left atrium was determined. Depiction of the left atrium was rated by two radiologists in consensus. A cardiologist segmented the MR data sets and rated depiction of the left atrium. RESULTS Five of 20 patients had irregular breathing patterns with navigator efficiency less than 35% and were excluded from evaluation. CNR was significantly higher for CE IR-SSFP compared with T2-prep SSFP (18.4+/-5.3 vs. 11.7+/-3.5, p<0.01). Depiction of the left atrium by T2-prep SSFP was rated as good in four patients, moderate in ten patients, and poor in one patient, whereas depiction of the left atrium by CE IR-SSFP was rated as excellent in nine patients, good in four patients, and moderate in two patients. CE IR-SSFP allowed for semiautomated segmentation of the left atrium in 15 patients, whereas T2-prep SSFP allowed for segmentation only in ten patients. CONCLUSION Gadofosveset trisodium-enhanced MRA of the left atrium is feasible with significantly improved image quality compared to noncontrast MRA.

Mechanical circulatory support for elderly heart failure patients

End-stage systolic heart failure is an increasingly common problem in elderly patients and is associated with high cost, poor quality of life, and poor outcomes. Mechanical circulatory support is a promising therapy as both a bridge to transplantation and destination therapy. Elderly patients are frequently ineligible for heart transplantation because of their age and comorbidities, and the application of mechanical circulatory support for destination therapy in this population is not well defined. A review of the literature was undertaken to better characterize our experience to date with mechanical circulatory support in older heart failure populations. Mechanical circulatory support is being employed increasingly for destination therapy indications in older patients. The newer continuous flow devices appear to have disproportionate advantage in elderly patients, which has translated into marked improvement in 1- and 2-year survival. The rational implementation of MCS devices in elderly heart failure patients needs to focus on (1) continuous flow devices that appear to have particular benefit in this population, (2) extensive pre-MCS assessment including variables relating to frailty, and (3) intervening before these patients develop cardiogenic shock. More data are needed on the cost-benefit analysis of routine use of CF devices as destination therapy in elderly patients with heart failure.