We performed a retrospective analysis of HCM patients followed regularly as outpatients in the cardiology department of a central hospital who underwent CMR with LGE study.

Of a population of 78 patients with HCM, 61 underwent CMR. The reasons for not undergoing CMR were the usual ones of ICD or pacemaker, claustrophobia, or patient refusal.

The definition of HCM was based on the classic echocardiographic criteria (left ventricular hypertrophy [LVH] without dilatation, maximum wall thickness ≥15 mm) and exclusion of other systemic or local causes of hypertrophy.

Eight patients were excluded: five in whom LGE study was not possible, one with a diagnosis of cardiac amyloidosis and two with Noonan syndrome. The final study population was thus composed of 53 patients.

The patients’ clinical data were collected from their medical records by an investigator blinded to the results of CMR.

The statistical analysis was performed with SPSS for Windows, version 17.0.

Nominal variables were expressed as counts and percentages and were compared (combination of frequencies) using the chi-square test. Continuous variables were expressed as means ± standard deviation; the Student's t test was used to compare variables with normal distribution and the Mann–Whitney U test to compare those with non-normal distribution.

A value of p<0.05 was considered statistically significant.

The study population consisted of 53 patients, 27 (50.9%) male, with a mean age of 56.4±17.0 years at the time of diagnosis.

Table 1 shows the main characteristics of the population. In terms of functional capacity, 29 (54.7%) patients were in NYHA class I, 22 (41.5%) in class II, and two (3.8%) in class III. No patient had undergone myectomy and two had undergone alcohol septal ablation.

Table 2 shows the main electrocardiographic alterations.

Of the 34 (64.1%) patients screened for Fabry disease, none had any of the classical mutations.

Investigation of HCM mutations in sarcomere protein genes, performed in 41 patients (77.4%), was negative in 12 (29.3%); a classical mutation was identified in nine (21.9%), a mutation of undetermined significance in three (7.3%), and the results are still awaited in 17 (41.5%).

Mean NT-pro-BNP, assessed in 29 patients (54.7%), was 3130±5762 pg/ml.

Only four (13.3%) of the patients who underwent exercise testing had a hypotensive response.

The phenotypic distribution of HCM was as follows: asymmetric in 36 (67.9%) patients, apical in 13 (24.5%) and concentric in four (7.5%). Systolic anterior motion of the mitral valve causing obstruction at rest was observed in 20 (37.7%) patients, with an end-systolic gradient of 69.4±27.3 mmHg. Mitral regurgitation was absent in six (11.3%) patients, minimal (grade 1) in 30 (56.6%), mild (grade 2) in 11 (20.8%), moderate (grade 3) in five (9.4%) and severe (grade 4) in one (1.9%).

Only seven (13.2%) patients did not present diastolic dysfunction. A pseudonormal pattern was the most common, found in 22 (41.5%) patients, followed by abnormal relaxation in 21 (39.6%); three (5.7%) presented a restrictive pattern.

At least mild global systolic dysfunction was identified in seven (13.2%) patients.

Table 3 shows the main continuous echocardiographic variables.

Of the 13 patients who underwent exercise echocardiography, seven (53.8%) developed a significant gradient on exertion (69.3±31.9 mmHg).

The phenotypic characterization of HCM by CMR was similar to that obtained by transthoracic echocardiography, and provided more accurate localization of LVH.

Table 4 shows the main continuous variables assessed by CMR.

LGE was observed in 24 (45.3%) patients.

Patients with LGE were younger at diagnosis (52.3±16.9 vs. 59.8±16.5 years; p=0.046), and more often had a family history of sudden death (33.3% vs. 3.4%; p=0.008; odds ratio [OR] 13.5).

Patients with LGE were more likely to have a history of coronary artery disease (12.5% vs. 0%; p=0.086) and higher NT-pro-BNP levels (5151±7882 vs. 1489±2422 pg/ml; p=0.089).

There were no differences between the groups in gender (p=0.669); history of hypertension (p=0.899), diabetes (p=0.532), syncope (p=0.288) or obstructive sleep apnea (p=0.135); presence of an identified mutation (p=0.676); NYHA functional class; previous therapy with beta-blockers (p=0.454) or non-dihydropyridine CCBs (p=0.112); voltage criteria for LVH (p=0.696); or history of atrial fibrillation (p=0.098).

There was also no difference between the groups in blood pressure response to exercise testing (p=0.348).

Patients with LGE more often presented systolic dysfunction on echocardiography, characterized by LVEF <50% (25.0% vs. 3.4%; p=0.038; OR 9.33) and diastolic dysfunction with pseudonormal (68.2% vs. 29.2%) or restrictive pattern (9.1% vs. 4.2%; p=0.011).

Table 5 shows the continuous echocardiographic variables that predicted LGE.

No association was seen between the presence of LGE and type of HCM: asymmetrical (p=0.441), apical (p=0.475) and concentric (p=0.844). Similarly, neither the presence of obstruction (p=0.242) nor the severity of mitral regurgitation (p=0.637) was associated with LGE.

Table 6 shows the CMR variables that predicted LGE.

Patients were followed for a mean of 53.6±53.4 months (4-271).

There were no differences between the groups in detection of non-sustained ventricular tachycardia (20.8% vs. 20.7%; p=0.990), or in the number of ventricular extrasystoles (p=0.503) documented on 24-hour Holter monitoring.

During follow-up 11 patients (20.7%) received an ICD for primary prevention due to the presence of one or more classical risk factors. More patients with LGE received ICDs (37.5% vs. 6.9%; p=0.015). An appropriate therapy with overdrive pacing was recorded in only one patient.

Two patients died during follow-up, one in each group, both from heart failure.

The mean age of our population (56.4±17.0 years) was older than in most studies in the literature5,11,12 and included few patients in the age-group most associated with sudden death (<35 years).

Most were asymptomatic or mildly symptomatic, as in other published series.9,13–15 This highlights the need for new ways to stratify risk of sudden death, since this may be the first clinical manifestation of HCM, years after initial diagnosis.16,17

Although asymmetric HCM was the most common pattern in our population (67.9%), there was a high prevalence of apical HCM (24.5%).

The mean maximum LV wall thickness on CMR of 19.4±3.8 mm demonstrates that significant LVH can be present even in only mildly symptomatic patients, as reported in the literature.13–15

The prevalence of LV outflow tract obstruction in our population (50.9%) was lower than in the literature,18 but some patients without a gradient at rest did not undergo exercise echocardiography.

The percentage of patients with a hypotensive response on exercise testing (13.3%) was also lower than previously reported (25%).19,20

Our study confirms that the presence of LGE is a common phenotypic characteristic in this population, although its prevalence (45.3%) was lower than that described in the literature.21–23

The pattern of distribution of LGE does not correspond to the perfusion territories of the epicardial coronary arteries, but is related to areas of LVH and is mid-myocardial in location.9

Predictors of LGE were younger age, a family history of sudden death, LVEF <50%, more severe diastolic dysfunction and LA dilatation, and greater maximum LV wall thickness.

It is known that the presence and extent of LGE is inversely related to LVEF,24 since LGE is associated with ventricular remodeling that eventually leads to heart failure.13 An association between LGE and maximum LV wall thickness has also been reported.25 LA dilatation, a surrogate marker of diastolic dysfunction, is also associated with LGE.26

Mortality in our population, although low, was in all cases of cardiovascular cause (heart failure).

As in previous studies,11,15 it remains to be proved whether LGE is an independent prognostic marker. Maron et al.12 reported a high prevalence, although not reaching statistical significance, of cardiovascular events during follow-up of 202 patients with HCM and LGE. By contrast, in a study of 220 asymptomatic or only mildly symptomatic HCM patients with a mean follow-up of three years, Bruder et al.15 showed that LGE was an independent predictor of cardiac death (hazard ratio [HR] 8.6; p=0.038), whereas the presence of one or two clinical risk factors did not reach statistical significance (HR 1.4; p=0.68).

In a recent meta-analysis of four studies with a total of 1063 HCM patients, Green et al.5 confirmed the high prevalence of LGE (60%) and its correlation with adverse cardiovascular events (cardiac death, heart failure death, and all-cause mortality), although it was not associated with sudden death or aborted sudden death and did not add value to traditional clinical risk factors.

In a population in which 60% present LGE and the event rate is 1–5%/year, such an association would be difficult to prove. More sophisticated techniques for quantifying LGE would thus improve its prognostic value.27 Quantification of the extent of LGE by means of T1-weighted sequences has been validated in other diseases of the myocardium, including ischemic heart disease and dilated cardiomyopathy, and could be of value in HCM.28,29

The European Cardiovascular Magnetic Resonance registry, with a clinical follow-up of at least 12 months, observed only a trend towards better outcome in HCM patients without LGE.30

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that they have followed the protocols of their work center on the publication of patient data.

The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.