Diastolic murmur in mid-ventricular obstructive hypertrophic cardiomyopathy: A case report

Abstract

A diastolic murmur is informative in the diagnosis of valvular heart disease, such as mitral stenosis and aortic regurgitation. Patients with hypertrophic cardiomyopathy (HCM) could have diastolic murmurs, although this is not widely recognized. We describe an illustrative case of HCM which was found to have a diastolic murmur associated with mid-left ventricular obstruction. An asymptomatic 65-year-old male was referred because of an abnormal electrocardiogram. Cardiac auscultation showed a soft fourth heart sound, a systolic ejection murmur, and a third heart sound followed by a diastolic murmur at the apex. On phonocardiography, the mid-diastolic murmur was predominantly low-pitched with an onset of about 200 ms after the second heart sound and a duration of approximately 150 ms. The timing of the diastolic murmur was consistent with an increased blood inflow during diastole in the mid-ventricular obstruction (2.0 m/s), which was produced by narrowing between the hypertrophied ventricular septum and the protrusion of the anterior papillary muscle.

<Learning objective: A diastolic murmur is common in valvular heart diseases, such as mitral stenosis and aortic regurgitation, and can also be heard in hypertrophic cardiomyopathy although not widely recognized. We report an illustrative case of hypertrophic cardiomyopathy with a diastolic murmur related to mid-left ventricular obstruction, findings that would highlight the importance of auscultation regarding not only the differential diagnosis but also risk stratification, given the possible association of diastolic murmurs with adverse outcomes, even in the era of advanced imaging techniques.>

Introduction

A diastolic murmur is characteristic of valvular heart diseases, such as mitral stenosis and aortic regurgitation, and is valuable in the differential diagnosis [1], [2]. Diastolic murmurs can also be heard in patients with hypertrophic cardiomyopathy (HCM) [3], [4], [5], [6], [7], although this is not widely recognized. Herein, we report an illustrative case with HCM, in whom a diastolic murmur was detected in association with mid-ventricular obstruction.

Case report

An asymptomatic 65-year-old male was referred to Matsushita Memorial Hospital because of an abnormal electrocardiogram. The patient had a history of dyslipidemia, hyperuricemia, and no family history of heart disease or premature sudden death. On examination, the blood pressure was 136/82 mmHg and the pulse was 75 beats per minute. Cardiac auscultation showed a soft fourth heart sound (S4), a systolic ejection murmur, and a third heart sound (S3). Of note, a diastolic murmur was clearly heard at the apex after the S3 (Data Supplement Sound). The reminder of the examination was normal. Medications included bezafibrate, allopurinol, and benzbromarone. An electrocardiogram showed normal sinus rhythm with a rate of 60 beats per minute, left axis deviation, left ventricular hypertrophy, and abnormal Q waves in leads V₃ and V₄. A chest radiograph was unremarkable, as was routine blood examination. The level of brain natriuretic peptide was 235.3 pg/ml.

A phonocardiogram, obtained at the apex in the left lateral decubitus position at a paper speed of 100 mm/s using a commercially available device (MES-1000, Fukuda-Denshi Co., Tokyo, Japan) [8], [9], showed a small S4 before the first heart sound (S1), a high-pitched, mid-to-late systolic crescendo murmur, and an S3 followed by a diastolic murmur (Fig. 1). The mid-diastolic murmur was predominantly low-pitched, accompanied by high-frequency components in the middle part, with an onset of about 200 ms after the second heart sound (S2) and a duration of approximately 150 ms although the precise assessment was not easy because of its overlap with S3.

Fig. 1.

Phonocardiography. A phonocardiogram obtained at the apex shows a fourth heart sound (S4) before the first heart sound (S1). A crescendo, mid-to-late systolic murmur is present (asterisk) predominantly in the high frequency and disappears before the second heart sound (S2). Note a diastolic murmur after the third heart sound (S3) in the low frequency (arrow). The middle part of the diastolic murmur has high-frequency components (arrowhead).

Transthoracic echocardiography revealed asymmetric septal hypertrophy with mid-ventricular systolic obstruction (Fig. 2). The systolic flow velocity in the mid-portion of the left ventricle was increased to 3.4 m/s, with no deterioration under the Valsalva maneuver. The mid-ventricular flow was also as high as 2.0 m/s even during diastole, findings consistent with the timing of the diastolic murmur as assessed by a simple phonocardiograph equipped in the echocardiograph. The mid-ventricular obstruction was likely to be produced by narrowing between the hypertrophied ventricular septum and the protrusion of the anterior papillary muscle. The apical wall motion was preserved without any thrombus, and a diastolic paradoxic jet flow from the apex toward the base of the left ventricle [10] was not detected. The transmitral E and A wave velocities as assessed by pulsed Doppler were 0.62 m/s and 0.47 m/s, respectively. Neither left ventricular outflow tract obstruction nor systolic anterior motion of the anterior mitral valve leaflet was found. Findings suggesting valvular heart disease, e.g. mitral stenosis or aortic regurgitation, and congenital heart disease, e.g. atrial septal defect or ventricular septal defect, were not detected. A diagnosis of mid-ventricular obstructive HCM was made.

Fig. 2.

Echocardiography. An apical four-chamber view at end-systole shows narrowing in the middle of the left ventricle (LV) (A). The mid-ventricular narrowing is also present even at end-diastole, approximately 10 mm in width, because of hypertrophy in the basal and mid-ventricular septum and the protrusion of the anterior papillary muscle (B, arrow), with preserved apical wall motion (B, asterisk). Increased blood flow velocities in the mid-ventricle are seen as aliasing on color M-mode both during systole and diastole (C, asterisk and dagger, respectively); the latter is likely to coincide with a diastolic murmur (arrow). The peak diastolic velocity is estimated to be 2.0 m/s on continuous Doppler (D). A flow toward the apex during early diastole (D, arrowhead) or the absence of a diastolic paradoxic jet flow denies a high pressure apical chamber. The positions of the cursor on color M-mode (C) and continuous Doppler (D) were not the same, as shown in the insets of Panels C and D. LA, left atrium.

Beta blocker, carvedilol, was administered to reduce the mid-ventricle obstruction and to prevent it from worsening in daily activities, although the patient had been asymptomatic and exercise stress echocardiography showed no deterioration in the mid-ventricular flow velocity. The mid-to-late systolic crescendo murmur has decreased, along with disappearance of the mid-diastolic murmur, after initiation of beta blocker therapy. The patient has been doing well without any cardiac events for more than 2 years.

Discussion

A mid-diastolic murmur is characteristic of mitral stenosis and tricuspid stenosis, although the latter is rare [1], [2]. Diastolic murmurs can also be heard in the setting of severe mitral regurgitation (i.e. Carey-Coombs murmur) [11] or severe aortic regurgitation (i.e. Austin Flint murmur) [12]. These conditions, however, appear to be ruled out in our case, since there were no suggestive findings on echocardiography. Other causes associated with mid-diastolic murmurs include atrial myxoma, calcified vegetation, atrial or ventricular septal defect, and mitral valve replacement [1], none of which was seen in the present case. It is intuitive that the diastolic murmur in our case was associated with mid-ventricular obstruction during diastole, given the fact that the diastolic murmur coincided with an accelerated inflow in the mid-left ventricle regarding the timing.

Auscultation in HCM patients with left ventricular outflow obstruction is characterized by the presence of S4 and systolic ejection murmurs, less frequently accompanied by S3 [13], as seen in our case. It is also important to note that a diastolic murmur is not uncommon among HCM patients – the incidence varies from 2% to 15% [3], [4], [5], [7]. The features of mid-diastolic murmurs related to HCM have been reported to be predominantly low-pitched and heard best or exclusively at the apex [5], [6], [7], findings consistent with the current patient. Hemodynamic studies showed that diastolic murmurs were significantly associated with impaired left ventricular compliance as assessed by end-diastolic pressure, peak negative dp/dt, and pressure–volume analysis in patients with non-obstructive HCM by Matsumura et al. [7].

Mid-ventricular obstruction, first reported by Falicov et al. in 1976 [14], is a rare form of obstructive HCM, and few data are available regarding diastolic murmurs in HCM patients with mid-ventricular obstruction. It is reported that an increased inflow velocity in the mid-ventricle was one of the causes of diastolic murmurs in a patient with mid-ventricular obstructive HCM, in which the inflow velocity was three times higher than the peak transmitral velocity (i.e. 1.2 m/s and 0.4 m/s, respectively) [15]. The same acceleration of mid-ventricular inflow was observed in our case (i.e. 2.0 m/s and 0.62 m/s, respectively). In such conditions, it may be reasonable to consider the possibility that the apical pressure during diastole would be lower than those in the base of the left ventricle, because that the mid-ventricle remained narrow even during diastole and that the apical wall motion was good without aneurysm formation. This speculation may be supported by the absence of a diastolic paradoxic jet flow in our case; diastolic high pressure in the apex is a promoter of the unique flow from the apex toward the base of the left ventricle during diastole, especially in the period of isovolumic relaxation [10]. The low-pressure apical chamber or “an apical suction effect” might be associated with the high-frequency components of the diastolic murmur in our case, given that the pitch of a heart murmur increases in accordance with an increase in pressure gradient [1]. Given that a mid-ventricular inflow during isovolumic relaxation finishes early in patients with HCM, compared to other conditions, e.g. normal hearts or aortic stenosis [16], more delayed relaxation in the basal part of the left ventricle than in the apex might be proposed as another cause of an increased inflow velocity in the mid-ventricle. Further research is needed to examine the association of diastolic murmurs with regional relaxation abnormalities in patients with HCM using speckle tracking echocardiography, which was not performed in our case.

In the examination of 10 HCM patients with mid-diastolic murmurs by Tominaga et al. [6], the mean onset of the mid-diastolic murmur was 130 ± 36 ms after the aortic component of S2, and the mean duration was 142 ± 36 ms. The onset timing, as compared with our case, is likely to be short whereas the duration is almost identical. The mechanism remains uncertain, but the delayed onset of the diastolic murmur in the current case may be due in part to differences in phenotype; all patients with mid-diastolic murmurs in their study had asymmetric septal hypertrophy and half of them had left ventricular outflow obstruction, whereas our case had no left ventricular outflow obstruction but mid-ventricular obstruction. Given the possible association of the presence of diastolic murmurs with adverse outcomes among HCM patients [7], we may safely consider that the present case highlights the importance of auscultation regarding not only the differential diagnosis but also risk stratification, even in the era of advanced imaging techniques.

Conflict of interest

None declared.