Downloaded from http://heart.bmj.com/ on July 1, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies
ORIGINAL ARTICLE
Cardiac magnetic resonance evaluation of left ventricular remodelling distribution in cardiac amyloidosis Eduardo Pozo,1,2 Anubhav Kanwar,1,3 Rajiv Deochand,1 Jose M Castellano,1 Tara Naib,1 Pablo Pazos-López,1,4,5 Keren Osman,6 Matthew Cham,7 Jagat Narula,1 Valentin Fuster,1,5 Javier Sanz1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-305710). For numbered affiliations see end of article. Correspondence to Dr Javier Sanz, Mount Sinai Hospital, One Gustave L Levy Place, Box 1030, New York, NY 10029, USA; [email protected] Received 14 February 2014 Revised 16 June 2014 Accepted 17 June 2014 Published Online First 10 July 2014
▸ http://dx.doi.org/10.1136/ heartjnl-2014-306221
To cite: Pozo E, Kanwar A, Deochand R, et al. Heart 2014;100:1688–1695. 1688
ABSTRACT Background Cardiac amyloidosis (CA) is associated with typical morphological features on echocardiography, including concentric LV hypertrophy (LVH). Cardiac magnetic resonance (CMR) can accurately depict anatomy in different cardiomyopathies. Our aim was to describe the morphological features and remodelling patterns of CA with CMR, and establish their diagnostic accuracy, as well as the value of traditional diagnostic criteria derived from echocardiography and electrocardiography. Methods Consecutive patients referred for CMR for possible CA were retrospectively evaluated. The diagnosis of CA was established in the presence of a positive cardiac biopsy and/or a typical pattern of myocardial late gadolinium enhancement. Morphological parameters were obtained from standard cine sequences. The presence and distribution of LVH, relative wall thickness (RWT) and LV remodelling patterns were determined. Results 130 patients (92 males (70.8%), age 64 ±13 years) were included. CA was diagnosed in 51 (39.2%). Patients with CA had increased LV wall thickness and LV mass index. An LV remodelling pattern different from concentric LVH was found in 42% of patients with CA, and asymmetric LVH was noted in 68.6%. A model including RWT, asymmetric LVH, and LVMI showed diagnostic accuracy of 88%, sensitivity of 67% and specificity of 86% for CA detection. Traditional diagnostic criteria for CA showed high specificity but poor sensitivity. Conclusions Asymmetric LVH and remodelling patterns different from concentric LVH are common in CA. Increased LV mass index, increased RWT, and asymmetric LVH are independently associated with the diagnosis. Traditional diagnostic criteria show poor sensitivity.
INTRODUCTION Cardiac amyloidosis (CA) is definitely diagnosed by the pathological demonstration of extracellular amyloid deposition in the myocardium.1 However, endomyocardial biopsy (EMB) is not widely available due to its invasive nature.2 Thus, EMB is frequently omitted in the presence of typical echocardiographic findings3–5 and extracardiac histological confirmation of amyloidosis.6 7 Although concentric LV hypertrophy (LVH) is commonly seen echocardiografically,8 9 it is not specific and
may indicate end-stage disease.10 The presence of low voltage on the ECG has increased specificity,11 but still lacks sensitivity12 in early stages. Recently, the presence of a typical pattern on late gadolinum enhancement (LGE) with cardiac magnetic resonance (CMR) has demonstrated variable sensitivity (69–97%) but particularly high specificity (94%) compared to EMB.13–15 Even without contrast, CMR may be an attractive alternative to echocardiography due to its more precise characterisation of tridimensional morphological and geometric changes in different cardiomyopathies.16 17 However, there is limited data on LV morphological and remodelling patterns with CMR in CA.18 We hypothesise that CMR can characterise these parameters and that they provide diagnostic value for the detection of CA in a contemporary population referred for CMR. We also evaluated the accuracy of ‘traditional’ diagnostic criteria.
METHODS Patient population Consecutive CMR studies performed in patients with clinical suspicion of CA at Mount Sinai Hospital from November 2007 to January 2013 were retrospectively identified. Repeated scans done in the same patient (n=6), and studies with real-time cine sequences (n=8) were excluded, resulting in a population of 130 patients (figure 1). The final diagnosis of CA was established by a positive EMB or, if not available, when a typical pattern of diffuse, predominantly subendocardial LGE with abnormal contrast kinetics was noted.13 This resulted in 51 patients fulfilling diagnostic criteria for CA. Low voltage on ECG was defined as the sum of precordial voltage (S on V1+R on V5 or V6) 0.42); (2) eccentric hypertrophy: LVH and normal RWT (≤0.42); (3) concentric remodelling: absence of LVH but abnormal RWT and (4) normal: absence of LVH and normal RWT. The ratio between LV mass and end-diastolic volume was quantified as an additional index of LV remodelling.21 We also measured LV wall
Figure 2 LV remodelling patterns. Criteria used to classify the patients into the different LV remodelling patterns. For each class there is an example of a short-axis cine image and the corresponding LGE.
Pozo E, et al. Heart 2014;100:1688–1695. doi:10.1136/heartjnl-2014-305710
1689
Downloaded from http://heart.bmj.com/ on July 1, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies thickness at different levels using end-diastolic short-axis cine images and registered maximal and minimal dimensions and their location in a standard 17-segment model. An asymmetry ratio was obtained by dividing the maximal by the minimal LV wall thicknesses within the same slice. Asymmetric LVH was considered present if one of the segments was ≥11 mm (males)/ ≥10 mm (females) in thickness20 and the asymmetry ratio was ≥1.322 or ≥1.5.23 Thus, the term, asymmetric LVH, was synonymous with ‘asymmetric increase in wall thickness’, independent of LV mass. The presence of pericardial or pleural effusions was also noted. LGE images were evaluated visually.
Traditional diagnostic criteria for CA Traditional diagnostic criteria were defined as the presence of low voltage on the ECG and typical echocardiographic findings. Typical echocardiographic findings were defined as the combination of concentric LVH, severe left atrial enlargement (left atrial volume index ≥40 mL/m2)5 and significant ( pseudonormal or restrictive) diastolic dysfunction.12
Statistical analysis Continuous variables were expressed as mean±SD or median [IQR] depending on their distribution, and categorical variables were described as total number ( percentages). When comparing patients with and without CA, χ2 test and Fisher exact tests were used for categorical variables where appropriate. Differences in normally and non-normally distributed continuous variables were established using a 2-tailed unpaired Student t and Mann– Whitney U tests, respectively. Morphological variables associated with the diagnosis of CA and clinically relevant interactions demonstrating statistical significance were included in a backward logistic regression analysis. All possible models were created using a macro for SPSS.24 The selection of the final model was based on statistical criteria (Mallows’ Cp statistic and area under the curve (AUC)), clinical plausibility, and parsimony. Predicted prevalence ratios (ratios of expected probability) were calculated for each variable of the final model and their combinations. Results were considered statistically significant when the 2-tailed p value was
Heart failure and cardiomyopathies
ORIGINAL ARTICLE
Cardiac magnetic resonance evaluation of left ventricular remodelling distribution in cardiac amyloidosis Eduardo Pozo,1,2 Anubhav Kanwar,1,3 Rajiv Deochand,1 Jose M Castellano,1 Tara Naib,1 Pablo Pazos-López,1,4,5 Keren Osman,6 Matthew Cham,7 Jagat Narula,1 Valentin Fuster,1,5 Javier Sanz1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-305710). For numbered affiliations see end of article. Correspondence to Dr Javier Sanz, Mount Sinai Hospital, One Gustave L Levy Place, Box 1030, New York, NY 10029, USA; [email protected] Received 14 February 2014 Revised 16 June 2014 Accepted 17 June 2014 Published Online First 10 July 2014
▸ http://dx.doi.org/10.1136/ heartjnl-2014-306221
To cite: Pozo E, Kanwar A, Deochand R, et al. Heart 2014;100:1688–1695. 1688
ABSTRACT Background Cardiac amyloidosis (CA) is associated with typical morphological features on echocardiography, including concentric LV hypertrophy (LVH). Cardiac magnetic resonance (CMR) can accurately depict anatomy in different cardiomyopathies. Our aim was to describe the morphological features and remodelling patterns of CA with CMR, and establish their diagnostic accuracy, as well as the value of traditional diagnostic criteria derived from echocardiography and electrocardiography. Methods Consecutive patients referred for CMR for possible CA were retrospectively evaluated. The diagnosis of CA was established in the presence of a positive cardiac biopsy and/or a typical pattern of myocardial late gadolinium enhancement. Morphological parameters were obtained from standard cine sequences. The presence and distribution of LVH, relative wall thickness (RWT) and LV remodelling patterns were determined. Results 130 patients (92 males (70.8%), age 64 ±13 years) were included. CA was diagnosed in 51 (39.2%). Patients with CA had increased LV wall thickness and LV mass index. An LV remodelling pattern different from concentric LVH was found in 42% of patients with CA, and asymmetric LVH was noted in 68.6%. A model including RWT, asymmetric LVH, and LVMI showed diagnostic accuracy of 88%, sensitivity of 67% and specificity of 86% for CA detection. Traditional diagnostic criteria for CA showed high specificity but poor sensitivity. Conclusions Asymmetric LVH and remodelling patterns different from concentric LVH are common in CA. Increased LV mass index, increased RWT, and asymmetric LVH are independently associated with the diagnosis. Traditional diagnostic criteria show poor sensitivity.
INTRODUCTION Cardiac amyloidosis (CA) is definitely diagnosed by the pathological demonstration of extracellular amyloid deposition in the myocardium.1 However, endomyocardial biopsy (EMB) is not widely available due to its invasive nature.2 Thus, EMB is frequently omitted in the presence of typical echocardiographic findings3–5 and extracardiac histological confirmation of amyloidosis.6 7 Although concentric LV hypertrophy (LVH) is commonly seen echocardiografically,8 9 it is not specific and
may indicate end-stage disease.10 The presence of low voltage on the ECG has increased specificity,11 but still lacks sensitivity12 in early stages. Recently, the presence of a typical pattern on late gadolinum enhancement (LGE) with cardiac magnetic resonance (CMR) has demonstrated variable sensitivity (69–97%) but particularly high specificity (94%) compared to EMB.13–15 Even without contrast, CMR may be an attractive alternative to echocardiography due to its more precise characterisation of tridimensional morphological and geometric changes in different cardiomyopathies.16 17 However, there is limited data on LV morphological and remodelling patterns with CMR in CA.18 We hypothesise that CMR can characterise these parameters and that they provide diagnostic value for the detection of CA in a contemporary population referred for CMR. We also evaluated the accuracy of ‘traditional’ diagnostic criteria.
METHODS Patient population Consecutive CMR studies performed in patients with clinical suspicion of CA at Mount Sinai Hospital from November 2007 to January 2013 were retrospectively identified. Repeated scans done in the same patient (n=6), and studies with real-time cine sequences (n=8) were excluded, resulting in a population of 130 patients (figure 1). The final diagnosis of CA was established by a positive EMB or, if not available, when a typical pattern of diffuse, predominantly subendocardial LGE with abnormal contrast kinetics was noted.13 This resulted in 51 patients fulfilling diagnostic criteria for CA. Low voltage on ECG was defined as the sum of precordial voltage (S on V1+R on V5 or V6) 0.42); (2) eccentric hypertrophy: LVH and normal RWT (≤0.42); (3) concentric remodelling: absence of LVH but abnormal RWT and (4) normal: absence of LVH and normal RWT. The ratio between LV mass and end-diastolic volume was quantified as an additional index of LV remodelling.21 We also measured LV wall
Figure 2 LV remodelling patterns. Criteria used to classify the patients into the different LV remodelling patterns. For each class there is an example of a short-axis cine image and the corresponding LGE.
Pozo E, et al. Heart 2014;100:1688–1695. doi:10.1136/heartjnl-2014-305710
1689
Downloaded from http://heart.bmj.com/ on July 1, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies thickness at different levels using end-diastolic short-axis cine images and registered maximal and minimal dimensions and their location in a standard 17-segment model. An asymmetry ratio was obtained by dividing the maximal by the minimal LV wall thicknesses within the same slice. Asymmetric LVH was considered present if one of the segments was ≥11 mm (males)/ ≥10 mm (females) in thickness20 and the asymmetry ratio was ≥1.322 or ≥1.5.23 Thus, the term, asymmetric LVH, was synonymous with ‘asymmetric increase in wall thickness’, independent of LV mass. The presence of pericardial or pleural effusions was also noted. LGE images were evaluated visually.
Traditional diagnostic criteria for CA Traditional diagnostic criteria were defined as the presence of low voltage on the ECG and typical echocardiographic findings. Typical echocardiographic findings were defined as the combination of concentric LVH, severe left atrial enlargement (left atrial volume index ≥40 mL/m2)5 and significant ( pseudonormal or restrictive) diastolic dysfunction.12
Statistical analysis Continuous variables were expressed as mean±SD or median [IQR] depending on their distribution, and categorical variables were described as total number ( percentages). When comparing patients with and without CA, χ2 test and Fisher exact tests were used for categorical variables where appropriate. Differences in normally and non-normally distributed continuous variables were established using a 2-tailed unpaired Student t and Mann– Whitney U tests, respectively. Morphological variables associated with the diagnosis of CA and clinically relevant interactions demonstrating statistical significance were included in a backward logistic regression analysis. All possible models were created using a macro for SPSS.24 The selection of the final model was based on statistical criteria (Mallows’ Cp statistic and area under the curve (AUC)), clinical plausibility, and parsimony. Predicted prevalence ratios (ratios of expected probability) were calculated for each variable of the final model and their combinations. Results were considered statistically significant when the 2-tailed p value was
