European Heart Journal – Cardiovascular Imaging (2015) 16, 423–432 doi:10.1093/ehjci/jeu225

Exercise echocardiography and cardiac magnetic resonance imaging to predict outcome in patients with hypertrophic cardiomyopathy† Jesu´s Peteiro1*, Xusto Fernandez2, Alberto Bouzas-Mosquera 1, Lorenzo Monserrat2, Cristina Me´ndez 3, Esther Rodriguez-Garcia 3, Rafaela Soler3, David Couto 1, and Alfonso Castro-Beiras 1 1

Department of Cardiology, Complexo Hospitalario Universitario de A Corun˜a (CHUAC) and INIBIC (Instituto de Investigacio´n Biome´dica de A Corun˜a), Universidad de A Corun˜a, P/ Ronda 5-48 izda, 15011 A Corun˜a, Spain; 2Unit of Cardiomyopathies, Complexo Hospitalario Universitario de A Corun˜a (CHUAC), Universidad de A Corun˜a, A Corun˜a, Spain; and 3 Department of Radiology, Complexo Hospitalario Universitario de A Corun˜a (CHUAC), Universidad de A Corun˜a, A Corun˜a, Spain Received 30 May 2014; accepted after revision 24 October 2014; online publish-ahead-of-print 26 November 2014



exercise echocardiography † hypertrophic cardiomyopathy † regional wall motion abnormalities † cardiac magnetic resonance



Several risk factors have been proposed to predict outcome in hypertrophic cardiomyopathy (HCM).1 Other likely risk factors have lately emerged like increased fibrosis demonstrated by cardiac magnetic resonance (CMR).2,3 Our group has also demonstrated that patients with HCM who develop wall motion abnormalities (WMAs) during exercise echocardiography (ExE) are at higher risk.4 The aims of this study were to evaluate ExE and CMR to predict outcome in HCM and to explore the relationships between both techniques.

Patients A group of 160 patients with clinical diagnosis of HCM which was being followed-up in our HCM unit and were referred for ExE and CMR according to a research protocol was considered. HCM was diagnosed by the presence of a non-dilated and hypertrophied left ventricle (LV) (wall thickness .15 mm in adult index patients or .13 mm plus abnormal electrocardiographic results in relatives) in the absence of another cardiac or systemic disease capable of producing the magnitude of LV

* Corresponding author. Tel: +34 81 176356; Fax: +34 81 178001, E-mail: [email protected]

Partially presented in the European Society of Cardiology Congress 2013, Amsterdam, The Netherlands.

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].

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We have observed that wall motion abnormalities (WMAs) during exercise echocardiography (ExE) are associated to events in hypertrophic cardiomyopathy (HCM). Our objective was to evaluate ExE and cardiac magnetic resonance (CMR) to predict outcome in HCM. ..................................................................................................................................................................................... Methods ExE and CMR were performed in 148 patients with HCM. During follow-up (7.1 + 2.7 years), there were 7 hard events and results (Hard-E) and 26 combined events (Comb-E). Exercise WMAs were observed in 13 patients (8.8%), perfusion defects in 10 (6.8%), and late gadolinium enhancement (LGE) in 48 (32.4%). WMAs were seen in 57% of patients with Hard-E vs. 6% without (P ¼ 0.001) and in 23 and 6% with and without Comb-E (P ¼ 0.005). Perfusion defects were also more frequent in patients with Hard-E than without (43 vs. 5%, P ¼ 0.007) and in patients with Comb-E than without (23 vs. 5%, P ¼ 0.002). LGE (g) was greater in patients with Comb-E than without [median (25th –75th percentile) 0 (0–21.1) vs. 0 (0–9.3) g P ¼ 0.04]. Univariable predictors of Comb-E included NYHA class ≥2, peak double product, DWMSI, and CMR data. Peak double product [Hazard ratios (HR) ¼ 0.99, confidence intervals (CI) 95% 0.99–0.99, P ¼ 0.02] and DWMSI (HR ¼ 404, CI 95% 12 –13681, P ¼ 0.001) remained independent predictors. Peak WMSI correlated with myocardial mass with LGE (r ¼ 0.20, P ¼ 0.02) and with perfusion defect area (r ¼ 0.40, P , 0.001). LGE affecting ≥15% of the left ventricle was observed in 38% of patients with exercise WMAs vs. 12% without (P ¼ 0.009). ..................................................................................................................................................................................... Conclusion CMR data are associated to exercise WMAs in patients with HCM. ExE and CMR may help to predict outcome in them.

424 hypertrophy observed.1,5 Patients with LV systolic dysfunction, defined as a resting LV ejection fraction (LVEF) ,50% (n ¼ 9), and patients who had either a history of coronary disease or evidence of coronary lesions on angiography (n ¼ 3) were excluded. The final study group consisted of 148 patients (122 index patients and 26 affected relatives). These patients represent a subset of a group of 239 patients with HCM who underwent ExE and had their data previously published.4 ExE and CMR were performed without knowledge of the other test results. Decisions regarding coronary angiographies were performed according to the responsible team. Informed consent was obtained for each patient.

Exercise echocardiography

ExE analysis LVEF at rest and at exercise were measured by the biplane Simpson’s rule.9 The LV was divided into 16 segments.10 A wall motion score index (WMSI) at rest and at exercise was calculated, with normal wall motion scoring ¼ 1, hypokinetic ¼ 2, akinetic ¼ 3, and dyskinetic ¼ 4. A WMSI . 1 defined the presence of WMAs. Inter- and intra-observer variabilities for the assessment of WMAs in patients with HCM have been previously reported by our group.4

Cardiac magnetic resonance Images were obtained with a 1.5-T system (Gyroscan NT Intera or Achieva; Philips Medical Systems, Best, The Netherlands) in conjunction with a phased-array body coil and ECG gating. Perfusion images were acquired in the short-axis plane from base to apex with an ECG-triggered T1-weighted inversion-recovery sequence (repetition time/echo time, 3.2/1.6 ms; flip angle, 508; FOV, 400 mm; voxel size, 3.12 × 3.25; section thickness, 8 mm). Gadopentetate dimeglumine, 0.05 mmol/kg of body weight (Dotarem, Guerbet, France), was injected at 4 mL/s and flushed with 20–25 mL of normal saline solution using a power injector. Forty dynamic scans were acquired simultaneously at each slice during the first pass of the contrast agent.11 Patients were instructed to hold their breath as long as possible and to breathe quietly when necessary. After the series of perfusion images was completed, another bolus of gadopentetate dimeglumine, 0.15 mmol/kg, was injected until achievement of a total dose of 0.2 mmol/kg for late gadolinium enhancement (LGE). LGE images were acquired 10 min after the injection of the contrast material with an inversion-recovery T1-weighted sequence12,13 (repetition time/echo time, 4.1/1.35 ms; inversion time, 200 – 400 ms), adjusted for each patient to achieve optimal suppression of normal myocardium;

flip angle, 158; FOV, 400 mm; voxel size, 1.66 × 1.85; and section thickness, 8 mm. Three series were acquired in the short axis, at the base, midventricle, and apex; and one series in the two- and four-chamber views.

CMR imaging analysis Images were analysed with image post-processing software (Viewforum, version 5.0; Philips Medical Systems) by two experienced radiologists, whose joint opinion was reached. LGE was considered present when the myocardial signal intensity was highly hyperintense and persists in the same slice after swapping the phase encoding, to exclude artefacts. LGE was then quantified with the QMass MRw software, version 7.1 (Medis medical imaging systems, Leiden, The Netherlands) and expressed as a percentage of the total LV mass. Signal intensity was measured as mean intensity plus standard deviations (SD) of mean for intra-individual analysis. Enhancement was defined as signal intensity .5 SD above the acquired mean signal intensity level.

Follow-up Follow-up and events were determined by revisiting the patients and reviewing medical records and death certificates. No patients were lost during follow-up. Hard events (Hard-E) included cardiac death, cardiac transplantation, appropriate defibrillator discharge, sustained ventricular tachycardia (VT), stroke in the context of atrial fibrillation/flutter, myocardial infarction, and heart failure requiring hospitalization. Cardiac death was defined as death due to acute myocardial infarction, congestive heart failure, life-threatening arrhythmias, or cardiac arrest; unexpected, otherwise unexplained sudden death was also considered cardiac death. Combined events (Comb-E) were defined as a Hard-E or new onset atrial fibrillation or syncope. Myectomy, septal ablation, defibrillator implantation, and demonstration of non-sustained VT (NSVT) were not considered events.

Statistical analysis Continuous variables were reported as mean + 1 SD for those following a normal distribution and as median and inter-quartile range for those following a non-normal distribution. Inter-group comparisons were performed by the Student t-test or the Mann– Whitney test as appropriate. Categorical variables were reported as percentages and inter-group comparisons performed by the x 2 or the Fisher exact tests. Event-free survival was estimated by the Kaplan– Meier method. Patients who died of non-cardiac causes were censored at the time of death. Univariable associations of variables with events were assessed with the Cox proportional hazards model. A P-value of ,0.05 was considered significant. Hazard ratios (HR) and 95% confidence intervals (CI) are given. Variables significantly associated to the end points in the univariable analyses were entered in a multivariable model. The value of ExE and CMR over clinical and exercise testing data was assessed by steps. The first step was based on clinical data and resting echocardiography. In the second step, the exercise testing variables were added. The third step consisted of the addition of ExE variables. In the final step, the CMR data were introduced. Continuous variables were used instead of dichotomous variables with similar meaning. Also, in case of variables with similar meaning, those with higher area under the receiver operator curves were chosen. To explore whether ExE and CMR provide incremental prognostic information compared with other established markers of adverse outcome in HCM, we also assessed three models in which we included the clinical predictors in step 1, then resting LVEF in step 2, and then increase in WMSI in step 3 for Model 1; % of the total LV mass with LGE for Model 2; and perfusion defect area for Model 3. Clinical variables in step 1 in these models were family history of sudden death, previous cardiac arrest or history of sustained VT, documented NSVT, previous syncope, blunted BP during exercise, maximal

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Medications were not withdrawn before ExE. Patients were encouraged to perform a treadmill exercise test (Bruce protocol 86%, other protocols 14%). Heart rate, blood pressure (BP), and a 12-lead electrocardiogram were obtained at baseline and at each stage of the protocols. End points included significant arrhythmia, severe hypertension (systolic BP .240 mmHg or diastolic BP .110 mmHg), hypotensive response (decrease .20 mmHg from baseline), or limiting symptoms. Two-dimensional echocardiography (Vivid 5, GE, Horten, Norway) was performed in standard views, at baseline and peak exercise.4,6 Peak ExE was performed when signs of exhaustion were present or an end point was reached. Left ventricular outflow tract and intra-ventricular gradients (mmHg) and mitral regurgitation (MR) were measured at rest and during the post-exercise period (1 min). Left ventricular outflow tract obstruction was defined as a gradient .30 mmHg. MR assessed by total jet area (in cm2 in the four-chamber apical view) was graded as trace, mild (1–4 cm2), moderate (4–8 cm2), or severe (.8 cm2), as described.7 Significant MR was defined as greater than or equal to moderate MR. Abnormal BP response was defined as a failure to increase systolic BP at least 20 mmHg during exercise or an initial increase with a subsequent fall of 20 mmHg.8

J. Peteiro et al.


Exercise echo and cardiac magnetic resonance in HCM

patients and as regional phenomena in 10, involving predominantly the antero-septal region (9/10). Coronary angiographies performed in 9/13 patients with exercise WMAs and in 18/135 patients without WMAs showed the absence of coronary lesions. A hypotensive response was not different among patients with or without exercise WMAs (46 vs. 33%), as it was the presence of significant MR at rest (15 vs. 16%) or at exercise (38 vs. 23%). LV wall thickness and left atrial diameter were also similar in patients with and without exercise WMAs (19 + 6 vs. 20 + 5 mm and 44 + 6 vs. 44 + 6 mm, respectively). Left ventricular outflow tract gradients at exercise were lower in patients with WMAs (10, 10–21, vs. 30, 10–100 mmHg, P ¼ 0.02). LVEF was also lower at rest and at exercise in patients with exercise WMAs (65 + 10 vs. 71 + 9 and 63 + 8 vs. 74 + 10, P ¼ 0.01 and P , 0.001, respectively), as it was exercise workload (8.5 + 2.3 vs. 10.5 + 3.3 METs, P ¼ 0.04). Peak WMSI correlated weakly with myocardial mass with LGE (r ¼ 0.20, P ¼ 0.02) and moderately with perfusion defect area (r ¼ 0.40, P , 0.001). Although there were no significant differences in LGE expressed as absolute or relative values between patients with and without exercise WMAs [0, (0–27.4) g vs. 0, (0–9.2) g; and 0, (0– 17.2)% vs. 0, (0–7.4) %], an extensive LGE signal, affecting ≥15% of

wall thickness, and resting left ventricular outflow tract (LVOT) obstruction. The incremental value between steps was measured by the x 2 method. Kaplan– Meier curves for the prediction of Comb-E, based on the presence or absence of exercise WMAs and the presence or absence of LGE, were generated.

Results Tables 1 and 2 show the baseline characteristics and resting and ExE parameters.

Exercise echocardiography ExE was performed without complications. Exhaustion was the more common reason for stopping the test (86.5%). Faintness and hypotension were the reasons for ceasing exercise in four patients. Six patients experienced dyspnoea and 12 angina.

Exercise WMAs and associations Exercise WMAs occurred in 13 patients (8.8%) and were more frequent in patients with events (Hard-E: 57 vs. 6%, P ¼ 0.001; Comb-E: 23 vs. 6%, P ¼ 0.005). These WMAs were described as global phenomena in 3

Table 1

Clinical baseline characteristics of 148 study patients with HCM All patients (n 5 148)

No events (n 5 122)

Combined events (n 5 26)

Value of P

Age (years) Male, n (%)

51 + 15 97 (65.5)

51 + 15 82 (67)

51 + 15 15 (58)

0.98 0.35

Family history of HCM (%)

44 (29.7)

36 (30)

8 (31)


Family history of SCD (%) Maximal LV thickness, mm

15 (10) 20 + 5

14 (11) 20 + 5

1 (4) 21 + 4

0.47 0.41


Left atrium diameter, mm

44 + 6

43 + 6

46 + 7


NYHA functional class ≥II, n (%) History of atrial fibrillation (%)

70 (47.3) 14 (9.4)

53 (43) 12 (10)

17 (65) 2 (8)

0.04 1.00

History of syncope, n (%)

13 (8.8)

10 (8)

3 (12)


History of angina, n (%) NSVT, n (%)

50 (33.8) 20 (13.5)

41 (34) 14 (11)

9 (35) 6 (23)

0.92 0.09

Sustained VT/SCD, n (%)

1 (0.7)

1 (0.8)

0 (0)


Implanted defibrillator, n (%) ≥2 risk factorsa

0 (0) 58 (39.2)

0 (0) 45 (37)

0 (0) 13 (50)

– 0.21

Atrial fibrillation, n (%) LBBB, n (%)

4 (2.7) 4 (2.7)

4 (3) 1 (0.8)

0 (0) 3 (12)

1.00 0.02

ST abnormalities, n (%)

62 (41.9)

49 (40)

13 (50)

0.36 0.12

Resting ECG, n (%)

Medications (%) Beta-blockersb

49 (33.1)

37 (30)

12 (46)

Calcium channel blockers

19 (12.8)

15 (12)

4 (15)


Disopyramide Amiodarone

4 (2.7) 8 (5.4)

3 (2) 8 (7)

1 (4) 0 (0)

0.54 0.35


33 (22.3)

26 (21)

7 (27)



16 (10.8)

10 (8)

6 (23)


ARB, angiotensin receptor blocker; ACEi, angiotensin-converting enzyme inhibitors; ECG, electrocardiogram; LBBB, left bundle branch block; NSVT, non-sustained ventricular tachycardia; SCD, sudden cardiac death; SVT, sustained ventricular tachycardia. a Defined as a family history of sudden death, previous cardiac arrest or history of sustained VT, documented non-sustained ventricular tachycardia on 24-h ECG monitoring, previous syncope, blunted BP during exercise testing, LV wall thickness ≥20 mm, and resting LVOT obstruction. b At the time of the ExE. Bold values indicate significant P value.

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Table 2

J. Peteiro et al.

Resting and exercise echocardiographic parameters


All patients (n 5 148)

No events (n 5 122)

Combined events (n 5 26)

Value of P

Clinical symptoms during test, n (%)

18 (12.2)

15 (12)

3 (12)


Positive ECG exercise testing, n (%) LV gradient at rest, mmHga

20 (13.5) 10 (9–25)

16 (13) 10 (9– 25)

4 (25) 10 (9– 40)

0.76 0.62

LV gradient .30 mmHg at rest (%)

35 (24)

28 (23)

7 (27)


LV gradient with exercise, mmHga LV gradient with exercise .30 mmHg, n

26 (10– 100) 66 (45)

22 (10–100) 53 (43)

33 (10–93) 13 (50)

1.00 0.54


Resting LVEF

71 + 9

71 + 9

70 + 10


Exercise LVEF Regional WMAs at rest (%)

73 + 10 3 (2)

73 + 10 1 (0.8)

73 + 12 2 (8)

0.67 0.08

Regional WMAs at exercise (%)

13 (9)

7 (6)

6 (23)


WMSI at resta WMSI at exercisea

1 (1 –1) 1 (1 –1)

1 (1–1) 1 (1–1)

1 (1–1) 1 (1–1.05)

0.02 0.003

D in WMSIa

0 (0 –0)

0 (0–0)

0 (0–0)


MR ≥ moderate at rest, n (%) MR ≥ moderate at exercise, n (%)

23 (15.5) 36 (24)

19 (16) 32 (26)

4 (15) 4 (15)

1.00 0.32


10.3 + 3.3

10.4 + 3.1

9.8 + 4.2


Peak HR, bpm Peak BP, mmHga

147 + 27 160 (140–180)

149 + 26 170 (140– 190)

138 + 31 155 (120– 180)

0.06 0.10

24 421 + 6984

25 035 + 6769

21 538 + 7383


90 (78– 97) 50 (34)

91 (79–98) 39 (32)

83 (71–94) 11 (42)

0.03 0.31

BP, blood pressure; HR, heart rate; LVEF, LV ejection fraction; MAPHR, maximal age-predicted heart rate; METs, metabolic equivalents; WMSI, wall motion score index. a Median and 25th– 75th percentiles are depicted. Bold values indicate significant P value.

the myocardium, was more frequent in the former (38 vs. 12%; P ¼ 0.009). Also, the percentage of patients with a perfusion defect was higher among those with WMAs (31 vs. 4.4%, P ¼ 0.006). Other associates of exercise WMAs were the presence of left bundle branch block (P ¼ 0.02) and lower exercise workload (P ¼ 0.04). After multivariable analysis, only the presence of a LGE signal affecting 15% of the myocardium was associated to an abnormal ExE [odds ratio (OR) 4.77, 95% CI 1.17–19.49, P ¼ 0.03]. Figures 1 and 2 (and corresponding Videos) are examples of normal and abnormal results by both ExE and CMR, respectively. Table 3 shows the clinical characteristics, ExE and CMR results, and events in patients with exercise WMAs.

CMR imaging and associations Ten patients (6.8%) had a perfusion defect (range: 0.5–17% of the myocardium) and 48 (32.4%) had LGE (range: 5–46% of the LV mass). Tables 4 and 5 depict CMR data in patients with and without Hard-E and Comb-E, respectively. CMR data exhibited a trend to be worse in patients with Hard-E than in those without. In contrast, CMR data were definitively worse in patients with Comb-E than in those without. Univariable associates of LGE were wall thickness (P , 0.001), left atrium diameter (P ¼ 0.01), ST-segment abnormalities on resting ECG (P ¼ 0.005), and lack of treatment with angiotensin receptor blockers/angiotensin-converting enzyme inhibitors (P ¼ 0.047). On multivariable analysis, only maximal wall thickness was associated to LGE (OR 1.10, 95% CI 1.02–1.19, P ¼ 0.02). On the other hand, a LGE signal affecting 15% of the LV mass was associated to left

atrium diameter (P ¼ 0.03), a history of NSVT (P ¼ 0.03), lower LV gradient at exercise (P ¼ 0.04), exercise WMAs (P ¼ 0.009), and peak WMSI (P ¼ 0.008) by univariable analysis. Both left atrium diameter and LVOT gradient at exercise remained independently associated with an extensive LGE (OR 1.12, 95% CI 1.03 – 1.22, P ¼ 0.01; OR 0.99, 95% CI 0.97–1.00, P ¼ 0.04, respectively), whereas the presence of exercise WMAs exhibited a trend towards this association (P ¼ 0.085).

Events During a follow-up of 7.1 + 2.7 years, 7 patients had a Hard-E (4 admissions due to cardiac failure, 2 strokes, 1 discharge of defibrillator) and 26 had a Comb-E (7 Hard-E, 12 new atrial fibrillation, 7 syncope). Univariable predictors of Hard-E were beta-blocker therapy (HR ¼ 4.53, 95% CI ¼ 1.01–20.3, P ¼ 0.049), peak double product (Pk-DP) (HR ¼ 0.99, 95% CI ¼ 0.99–0.99, P ¼ 0.04), % achieved of the maximal age-predicted heart rate (HR ¼ 0.03, 95% CI ¼ 0.00–0.68, P ¼ 0.04), D in WMSI (HR ¼ 220, 95% CI ¼ 4 –13100, P ¼ 0.01), perfusion defect area (HR ¼ 1.16, 95% CI ¼ 1.03 –1.31, P ¼ 0.02), and myocardial mass with LGE. (HR ¼ 1.07, 95% CI ¼ 1.01–1.13, P ¼ 0.03). No further analysis was performed due to the limited number of patients with Hard-E. Univariable and multivariable predictors of Comb-E are listed in Table 6. After adjustment, Pk-DP and DWMSI remained independent predictors, whereas LGE expressed as a percentage of the total LV mass exhibited a trend to be significant. Septal ablation or myectomy

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Peak rate pressure product, bpm mmHg % achieved of the MAPHRa Abnormal BP response, n (%)


Exercise echo and cardiac magnetic resonance in HCM

diomyopathy. No late gadolinium enhancement signals are seen in the three short-axis views (A – C). The resting (D) and the exercise studies (E) indicate normal LV response to exercise with LV cavity reduction during the systolic period and absence of wall motion abnormalities. Diastolic frames in the four- and two-chamber apical views are shown on the top of each stage (rest and exercise); systolic frames in these same views at the bottom. Supplementary data online, Video S1 correspond to the exercise echocardiography study of this patient.

were only performed in four patients who did not have events and in one who had a Comb-E, and defibrillator implantation in six and four patients without and with Hard-E, respectively. Figure 3 shows Kaplan–Meier curves according to the presence or absence of exercise WMAs and of LGE. The worst outcome was found in patients with positive results by both techniques. ExE data (DWMSI) and perfusion defect area by CMR increased the value of clinical risk factors and resting LVEF for predicting events, whereas LGE expressed as a percentage of the total LV showed a trend to increase the value of these variables for predicting events (Figure 4).

Discussion In this observational study of 148 patients with HCM who were evaluated by ExE and CMR, 8.8% of the patients had exercise WMAs, 6.8% had perfusion defects, and 32.4% LGE, although an extensive involvement was observed in only 14.2%. Pk-DP and D in WMSI remained independent predictors of Comb-E, whereas there was a trend for LGE expressed as a percentage of the LV mass to be a predictor.

Previous studies with CMR LGE has been found previously in more than half of the patients with HCM2,3,14 – 16 which is higher than in the current research, likely because we excluded patients with LV systolic dysfunction and with coronary artery disease. In one study, HCM patients at high risk according to clinical predictors had more frequent LGE signal and LV systolic dysfunction.14 Also, Rubinshtein et al. 16 showed that independent associates of LGE were depressed LVEF and increased septal thickness. Fibrosis enhancement has been found to be associated to overall mortality2 and to malignant arrhythmias in HCM.3 We hypothesize that the presence of myocardial fibrosis might impair LV response to exercise, therefore explaining the associations between exercise WMAs and abnormal CMR.

LV dysfunction during exercise Myocardial ischaemia, LV diastolic dysfunction, LVOT obstruction, or impaired inotropic reserve might explain the occurrence of WMAs. Myocardial ischaemia is the explanation suggested in many studies that evaluated HCM patients by radionuclides during exercise.8,17 – 19

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Figure 1 Normal cardiac magnetic resonance (A– C) and normal LV function at rest (D) and at exercise (E) in a patient with hypertrophic car-


J. Peteiro et al.

On the other hand, we did not observe an association between exercise WMAs and LVOT obstruction. Okeie et al. 18 also failed to find an association between LV function and obstruction during stress, whereas others found this association in a small series of patients.20 However, patients with resting LVOT obstruction were excluded in most of the studies that measured LV systolic function during exercise.8,17,18 The frequency of LV systolic dysfunction during exercise in HCM ranges from 8 to 43%.17,18 Centres admitting the most symptomatic patients might detect the highest number. In addition, exercise LV dysfunction may be more prevalent in certain genetic disorders like troponin gene mutations.21 Finally, although not explored in this research, other methods to evaluate myocardial function during exercise such as speckle tracking might predict outcome. In this regard, LGE has been recently found to be associated to depressed longitudinal function during exercise in patients with HCM.22 In a previous ExE study by our group that included 239 patients with HCM, the frequency of exercise WMAs was 7.9%,4 which is

similar to the actual report. ExE predicted worse outcome in this previous report. In the current analysis, ExE maintained its power to predict events, whereas CMR data exhibited a trend to be associated to poorer outcome.

LVOT obstruction Although LVOT obstruction may correlate with symptoms and response to exercise, we did not find an association between exercise LVOT obstruction and exercise WMAs, nor between LVOT obstruction and events. There have been conflicting results regarding the association between LVOT obstruction and events with studies that have found a higher probability of events in patients with LVOT obstruction23 and others that have not.24 Currently, a LVOT gradient ≥30 mmHg is considered a secondary marker for events.1

Limitations As in many studies dealing with outcome in HCM, the main limitation is the reduced number of events. This is particularly true for this

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Figure 2 Abnormal cardiac magnetic resonance (A – C) and abnormal LV response to exercise in a patient with hypertrophic cardiomyopathy. Late gadolinium enhancement signals are seen in the three short-axis views (A – C). The resting echocardiographic study was normal (D), whereas during exercise, extensive wall motion abnormalities developed (E). Diastolic frames in the four-chamber apical and long-axis views are shown on the top of each stage (rest and exercise); systolic frames in these same views at the bottom. Supplementary data online, Video S2 correspond to the exercise echocardiography study of this patient.


CMR data according to Hard-E Value of P

0 (0 –9)

5 (0– 33)


0 (0 –8)

7 (0– 16)


19 (14)

2 (29)


44 (31)

4 (57)

2 2 2 2 2 2 2 0 0 0 17.2 0 0 0 2 2 + 2 2 2 2 1.19 1.19 1.13 1.13 1.13 1.13 1.13


0 (0 –0)

0 (0– 7.1)

Any perfusion defect, n (%) Any perfusion defect and/or LGE, n (%)

7 (5)

3 (43)


46 (33)

4 (57)


Exercise echocardiography and cardiac magnetic resonance imaging to predict outcome in patients with hypertrophic cardiomyopathy.

We have observed that wall motion abnormalities (WMAs) during exercise echocardiography (ExE) are associated to events in hypertrophic cardiomyopathy ...
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