Amyl Nitrite During Echocardiography

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Amyl nitrite is a volatile fluid that is administered by crushing open an ampule.

The patient is asked to take repeated deep breaths through the mouth for about 20 seconds.

To prevent lingering odor and further dissemination from the crushed ampule into the room air, there should be proper ventilation with an electric fan, and the used ampule should be quickly discarded into a cup of water.


Echocardiography 2000 Feb;17(2):105-8
Inhalation of amyl nitrite and the measurement of left ventricular outflow velocity: studies in normal, young adults.
Vandenberg BF, Zink MH, Ayres RW, Lindower PD, Rath LS, Lewis J.
Prairie Cardiovascular Consultants, P.O. Box 19420, Springfield, IL 62740, USA.

Amyl nitrite inhalation is useful in the identification of patients with provocable left ventricular (LV) outflow tract obstruction. However, there are no prospective studies that assess the normal change in LV outflow velocity during this intervention. Eighteen normal subjects (mean age, 34+/-5 years; 9 men and 9 women) inhaled amyl nitrite during measurement of LV outflow velocity. Peak velocity increased from 109+/-16 cm/s to 144+/-24 cm/s (P<0.001). There were no significant gender differences in velocity measurements at baseline or at peak. Our study provides prospective data that may be useful when evaluating young adults for LV outflow tract obstruction with Doppler echocardiography during amyl nitrite inhalation.

J Am Soc Echocardiogr 1999 Feb;12(2):129-37
Color M-mode Doppler flow propagation velocity is a relatively preload-independent index of left ventricular filling.
Garcia MJ, Palac RT, Malenka DJ, Terrell P, Plehn JF.
Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Standard Doppler indexes of transmitral filling vary in response to alterations in left ventricular (LV) relaxation or preload. To determine whether color M-mode Doppler flow propagation velocity (vp), a new index of LV relaxation, is affected by preload, we obtained LV volumes, standard Doppler filling indexes, and vp in 20 patients at baseline, during Trendelenburg's position, inverse Trendelenburg's position, and after inhalation of amyl nitrite . LV end-diastolic volume decreased from 111 +/- 41 mL at baseline and 116 +/- 43 mL during Trendelenburg's position, to 104 +/- 40 during inverse Trendelenburg's maneuver and 92 +/- 33 mL after inhalation of amyl nitrite (P <.0001). Peak early filling velocity decreased from 79 +/- 19 cm/s and 90 +/- 20 cm/s to 73 +/- 22 cm/s and 64 +/- 20 cm/s, respectively (P < 0.0001). In contrast, no significant changes were found in vp (48 +/- 24 and 50 +/- 26 cm/s vs 48 +/- 25 and 48 +/- 25 cm/s). We conclude that vp is not affected significantly by preload. Thus vp may provide a more reliable and independent assessment of LV relaxation.

J Pharmacol Exp Ther 1997 Jan;280(1):326-31
Vascular and hemodynamic differences between organic nitrates and nitrites.
Bauer JA, Nolan T, Fung HL.
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, USA.

Because nitroglycerin (NTG, an organic nitrate) and isoamyl nitrite have similar chemical structures and a common mechanism of vascular relaxation (i.e., conversion to nitric oxide in vascular tissues and activation of guanylyl cyclase), it has often been assumed that organic nitrates and nitrites have identical pharmacologic actions. Because recent studies have shown that the vascular enzymes responsible for nitric oxide generation from organic nitrates and nitrites are distinct, we hypothesized that the in vitro vascular actions, in vivo hemodynamic effects and tolerance properties (both in vitro and in vivo) would be different as well. Isolated blood vessel studies showed that NTG provided more stable relaxation effects than ISAN, was more potent and caused greater in vitro vascular tolerance. Because the mechanism(s) of vascular tolerance in vitro may not be the same as those occurring in vivo, we also compared the left ventricular hemodynamic effects and tolerance properties of NTG vs. isoamyl nitrite and in congestive heart failure rats. Constant NTG infusion (10 micrograms/min) caused initial reductions in left ventricular end-diastolic pressure of 45 to 55%, which returned to baseline within 10 hr (tolerance development). In contrast, isobutyl nitrite and isoamyl nitrite (45 micrograms/min) caused initial reductions in left ventricular end-diastolic pressure similar to NTG (42-58%), but these hemodynamic effects of organic nitrites were maintained even when infusions were carried out to 22 hr. These results show that organic nitrites and organic nitrates are not pharmacologically identical (in vitro or in vivo), and may suggest a therapeutic advantage for organic nitrites in the treatment of some cardiovascular diseases.

Am J Cardiol 1996 Sep 15;78(6):662-7
Resting echocardiographic features of latent left ventricular outflow obstruction in hypertrophic cardiomyopathy.
Nakatani S, Marwick TH, Lever HM, Thomas JD.
Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.

We determined resting echocardiographic features predictive of latent left ventricular (LV) outflow obstruction in 50 consecutive patients with nonobstructive hypertrophic cardiomyopathy (26 provocable, 24 nonprovocable with amyl nitrite inhalation) to have a better understanding of the pathophysiology of this condition and to identify such patients without pharmacologic provocation. Measurements included wall thickness, type of hypertrophy, LV outflow tract diameter, degree of mitral systolic anterior motion, outflow pressure gradient, and ventricular volume. The direction of the ejection streamline was measured to assess the magnitude of the drag force acting on the mitral valve. Thirteen of 16 patients (81%) with proximal septal bulge were provocable, whereas only 3 of 8 patients (38%) with asymmetric septal hypertrophy and 10 of 26 (38%) with concentric hypertrophy were provocable (p < 0.05). LV outflow tract was significantly narrower and the angle between the ejection flow and the mitral valve was larger in provocable patients. The sensitivity for predicting provocable patients by a combination of a narrow outflow tract (< or = 2 cm) and a large angle (> or = 35 degrees) was 65%, with a specificity of 80% and a positive predictive value of 79%. When these criteria were combined with the presence of septal bulge, the sensitivity was 35%, but the specificity and the positive predictive value were both 100%. Patients with nonobstructive hypertrophic cardiomyopathy with proximal septal bulge, a narrow LV outflow tract, and an oblique angle between the ejection flow and the mitral valve appeared to be predisposed for latent outflow obstruction. These features are consistent with the presence of the large Venturi and drag forces. Thus, the left ventricle, which is capable of increasing both the Venturi and the drag forces on the basis of the morphologic change, contributes to the development of outflow obstruction with amyl nitrite inhalation.

Clin Cardiol 1996 Feb;19(2):121-7
Clinical significance of the apical late systolic ejection murmur: a new phonocardiographic sign indicating dynamic mid-left ventricular obstruction.
Fukuda N, Oki T, Iuchi A, Tabata T, Manabe K, Kageji Y, Sasaki M, Yamada H, Ito S.
Second Department of Internal Medicine, University of Tokushima, Japan.

Systolic ejection murmurs of the left heart usually have their peak during early to mid-systole. Few reports have addressed ejection murmurs with their peak at late systole. We evaluated the clinical significance of an apical systolic ejection murmur with a peak intensity during late systole using Doppler and two-dimensional (2-D) echocardiography and phonocardiography. The apical late systolic ejection murmur was observed in 9 of 13 consecutive patients with mid-left ventricular obstruction. We investigated the ejection flow velocity and the timing of maximum velocity at the three different sites of the left ventricle, the left ventricular cavity shape, and the timing of the peak murmur intensity in these nine patients (late-murmur group). The same parameters were also examined in 8 consecutive patients with mid-systolic ejection murmurs (mid-murmur group), 10 with early systolic ejection murmurs (early-murmur group), and 7 controls without murmurs. Patients with aortic stenosis were excluded. The mid-ventricular ejection flow velocity was significantly higher in the late-murmur group than in the other three groups; that of the outflow tract was markedly higher in the mid-murmur group. The ejection flow velocity at the aortic orifice of patients in the early-murmur group was significantly high compared with that of the controls. The timing of the peak murmur intensity in each group correlated with that of the peak flow signal at the corresponding site with maximum velocity. In all patients in the late-murmur group, 2-D echocardiography revealed a systolic narrowing of the cavity at the mid-ventricle. Amyl nitrite inhalation induced a marked increase in the intensity of the murmur without evidence of appearing or increasing mitral regurgitation. It was concluded that the apical ejection murmur with a late systolic peak intensity is a new phonocardiographic sign indicative of dynamic, mid-left ventricular obstruction. This murmur should be differentiated from the mitral regurgitant murmur.

Am J Cardiol 1995 Apr 15;75(12):805-9
Provocation of latent left ventricular outflow tract gradients with amyl nitrite and exercise in hypertrophic cardiomyopathy.
Marwick TH, Nakatani S, Haluska B, Thomas JD, Lever HM.
Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.

Amyl nitrite may be used to provoke latent gradients in patients with hypertrophic cardiomyopathy (HC) without significant resting outflow tract gradients, but afterload reduction may not be comparable to a more physiologic stressor such as symptom-limited exercise testing. This study compared the ability of amyl nitrite and exercise testing to provoke outflow tract gradients in 57 patients (40 men and 17 women, mean age +/- SD 49 +/- 16 years) with HC (septal thickness 19 +/- 5 mm, average resting gradient 13 +/- 10 mm Hg) who underwent echocardiography at rest, after amyl nitrite inhalation, and after maximal exercise. No significant gradient (< 50 mm Hg) was induced after either provocation in 26 patients (46%); in 15 patients (26%), inducibility was achieved after both stressors, in 6 (11%) after exercise only, and in 10 (18%) after amyl only. Patients with amyl-induced gradients differed from those in whom gradients were noninducible on the basis of smaller outflow tract dimensions (p < 0.001), larger resting gradients (p < 0.001), and a greater prevalence of "septal bulge" morphology (p = 0.02). Those with exercise-induced gradients were able to attain a greater workload (p = 0.07), have larger resting gradients (p = 0.02), and also tended to have a septal bulge morphology (p < or = 0.01). Although outflow tract obstruction increased to similar levels after amyl nitrite (49 +/- 39 mm Hg) and symptom-limited exercise (47 +/- 39 mm Hg), gradients induced by exercise and amyl correlated poorly (r = 0.54). (ABSTRACT TRUNCATED AT 250 WORDS)

J Cardiol 1994 Jul-Aug;24(4):299-309
Phonocardiographic and Doppler echocardiographic study on the mechanism of the presystolic murmur in mitral stenosis, especially the relationship to mitral inflow dynamics
Tabata T, Fukuda N, Iuchi A, Oki T.
Second Department of Internal Medicine, University of Tokushima School of Medicine.

The cause of the "presystolic murmur" in mitral stenosis was investigated by phonocardiography and continuous wave Doppler echocardiography in 31 patients with mitral stenosis and sinus rhythm classified into two groups: 18 patients with and 13 without "presystolic murmur". 1. The "presystolic murmur" group demonstrated high frequency vibrations preceding the first heart sound coinciding with the initial low frequency component of the first heart sound recorded at the apex in both groups. 2. There were two types of "presystolic murmur": The first type observed in three of the 18 patients occurred during the accelerated phase of the atrial (A) wave of mitral inflow signals and lasted until the first heart sound. The A wave velocity in mitral inflow signals was high at the onset and peak, and rapidly decreased after the peak. The second type observed in 15 patients occurred during the decelerated phase of the A wave and lasted until the first heart sound. The A wave velocity in mitral inflow signals was low at the onset, but high at the peak and rapidly decreased after the peak. 3. The mitral orifice area tended to be smaller in all patients with "presystolic murmur". The peak flow velocity, deceleration rate of the A wave, and maximal pressure gradient across the mitral valve during atrial contraction were significantly increased in all patients with "presystolic murmur". 4. Five patients with newly developed "presystolic murmur" after amyl nitrite inhalation had an increased initial low frequency component of the first heart sound coinciding with the latter half of "presystolic murmur". The rate of increase in the peak flow velocity and the deceleration rate of the A wave were significantly larger and the maximal atrioventricular pressure gradient during atrial contraction tended to be larger in these five patients than those in five who did not develop "presystolic murmur". 5. The peak flow velocity, deceleration rate of the A wave and the maximal atrioventricular pressure gradient during atrial contraction had increased 1 year later compared with those immediately after cardioversion of atrial fibrillation, and newly developed "presystolic murmur" appeared according to the recovery of left atrial mechanical function. These results suggest that the latter half of "presystolic murmur" originates from augmentation and prolongation of the initial low frequency component of the first heart sound up to the audible range caused by the sudden deceleration of mitral inflow velocity due to left ventricular contraction, and that the early half of "presystolic murmur" is the atriosystolic murmur produced by the increase in mitral inflow velocity during atrial contraction.

J Am Soc Echocardiogr 1994 Jul-Aug;7(4):388-93
Comparison of velocity and volumetric indexes of left ventricular filling during increased heart rate with exercise and amyl nitrite.
Percy RF, Conetta DA.
Division of Cardiology, University of Florida College of Medicine, University of Florida Health Science Center-Jacksonville 32209.

Physiologic variables, such as heart rate, affect the noninvasive indexes of left ventricular filling, complicating the interpretation of these indexes for clinical assessment of diastolic function. We compared the effect in normal subjects of increased heart rate provoked by both exercise and amyl nitrite on noninvasive velocity and volumetric indexes of left ventricular filling. Velocity indexes were affected in a different pattern with exercise compared with amyl nitrite because peak E wave velocity and relative atrial contribution to filling increased with exercise. In contrast, the volumetric index of rapid left ventricular filling increased similarly with both mechanisms. These findings demonstrate the importance of recognizing the different effects on indexes of left ventricular filling when heart rate is increased by different methods.

Clin Cardiol 1993 Apr;16(4):331-8
Subtle features of the hemodynamic response to amyl nitrite inhalation: new aspects of an old tool.
Moody JM Jr, Bailey SR, Rubal BJ.
Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234-6200.

Although amyl nitrite inhalation (ANI) antedates all current short acting vasodilators as a clinically useful pharmacologic stressor, few clinicians are aware of the subtle hemodynamic actions of this agent. This study examined transients in left and right heart hemodynamics after ANI in seven men (ages 44 +/- 7 years) undergoing elective cardiac catheterization. High-fidelity central aortic (AoP), left ventricular (LVP), pulmonary artery (PAP), right ventricular (RVP), and right atrial (RAP) pressures were simultaneously recorded from left and right heart multisensor catheters. As expected, ANI caused an acute fall in Ao pressure (27%; p < 0.01) and reflex tachycardia (p < 0.001). Little change was noted in PAP, RVP, RAP, or LV end-diastolic pressures or the time constant of LV isovolumetric relaxation (tau). LV ejection time decreased 23 +/- 10 ms (p < 0.05) and RV ejection time did not change. Baroreflex sensitivity was similar during pressure fall and recovery (6.4 +/- 4.5 vs. 6.1 +/- 3.6 ms/mmHg), however hysteresis (p < 0.05) was noted. Aortic pressure waveforms also changed following ANI. Changes were determined to be in part a consequence of the attenuation and delay in arterial wave reflections. This study extends the understanding of the complex nature of the hemodynamic response associated with ANI.

J Am Soc Echocardiogr 1993 Mar-Apr;6(2):142-8
Pharmacodynamic Doppler determination of mitral valve area in patients with significant aortic regurgitation.
Mego DM, Johns JP, Rubal BJ.
Cardiolgy Service, Brooke Army Medical Center, Fort Sam Houston, TX 78234-6200.

In patients with combined mitral stenosis (MS) and aortic regurgitation (AR), the Doppler-determined mitral valve area (MVA) may be overestimated due to a shorter than expected pressure half-time. We performed Doppler echocardiography at baseline and after inhalation of amyl nitrite in 10 patients with combined MS and AR (Group I) and in five patients with MS alone (Group II). AR severity was reduced by amyl nitrite inhalation in all Group I patients, with a decrease in mean jet height/LVOT ratio from 32% to 21% (p < 0.01). Pressure half-time increased in Group I after amyl nitrite, with a mean reduction in the calculated MVA of 0.15 cm2 (p < 0.01). Group II had no significant changes in pressure half-time or Doppler-determined MVA after amyl nitrite, whereas both groups had comparable increases in heart rate, mean transmitral velocity, and mean transmitral pressure gradient. In patients with combined MS and AR, we conclude that amyl nitrite significantly increases pressure half-time while reducing the severity of AR. These findings support earlier reports of MVA overestimation when pressure half-time is used in the presence of AR.

Chest 1990 Feb;97(2):389-95
Use of Doppler echocardiography and amyl nitrite inhalation to characterize left ventricular outflow obstruction in hypertrophic cardiomyopathy.
Sheikh KH, Pearce FB, Kisslo J.
Department of Medicine/Cardiology, Duke University Medical Center, Durham, NC 27710.

The presence of left ventricular outflow tract obstruction (LVOTO) of either a resting or dynamic nature may have important therapeutic and prognostic implications in patients with hypertrophic cardiomyopathy (HCM). Doppler echocardiograms combined with amyl nitrite (Amyl) inhalation were performed in 333 consecutive patients referred for suspected HCM to diagnose and categorize the nature and severity of LVOTO. Hypertrophic cardiomyopathy was present by 2-D and M-mode criteria in 145/333 (44 percent) patients. Normal limits of resting and post-Amyl continuous wave Doppler peak left ventricular outflow tract velocities were established in 15 subjects with completely normal 2-D and Doppler echocardiograms. Based on these criteria, of the 145 patients with HCM, 63 (43 percent) were classified as having resting LVOTO, peak velocity 4.2 +/- 1.3 m/s. Among 82 patients with HCM without resting LVOTO, 47 (57 percent) received Amyl. Latent LVOTO was provoked in 25/47 (53 percent), peak post-Amyl velocity 4.5 +/- 1.2 m/s. The remaining 22 (47 percent) had nonobstructive HCM, as indicated by no significant increase in post-Amyl velocity. Among a total 62 subjects receiving Amyl, none experienced serious morbidity or mortality. Doppler echocardiography, in conjunction with Amyl inhalation in selected patients, is a useful noninvasive method to diagnose and categorize patients with HCM according to the nature and severity of LVOTO.

Minerva Cardioangiol 1989 Apr;37(4):169-78
Dynamic phonocardiography in the study of mitral valve prolapse. Our experience]
Filice I, Gandolfo A, Buscaglia GB, Gazzarata M, Martinengo E.

The purpose of this paper is to check the usefulness of dynamic phonocardiography for mitral valve prolapse (MVP) diagnosis, especially in apparently silent cases, or with late-systolic click. In fact, possible MVP or mitral valve regurgitation can be shown. 148 patients (58 males, 90 females) have been examined by basal and dynamic phonocardiography and M-echocardiography. Patients were recruited for routine medical examination or during investigations for other causes or to explain evocative MVP troubles. Provocative tests by amyl nitrite, isoproterenol and methoxamine registered a late-systolic click in 17 normal cases and a late-systolic murmur in 22. M-echo demonstrated MVP in 142 cases (96%), with a slight prevalence of late-systolic MVP; tricuspid valve prolapse coexisted in 8 cases and aortic regurgitation in 12. Today echocardiography is the most important examination, but all our data point to the usefulness of dynamic phonocardiography for MVP diagnosis: in our opinion, the integration of both techniques represents the most correct approach.

N Engl J Med 1988 Jun 16;318(24):1572-8
Bedside diagnosis of systolic murmurs.
Lembo NJ, Dell'Italia LJ, Crawford MH, O'Rourke RA.
Department of Medicine, University of Texas Health Science Center at San Antonio.

The diagnostic accuracy of bedside maneuvers in the evaluation of patients with systolic murmurs has not been assessed objectively. Therefore, we evaluated 50 patients with documented systolic murmurs and compared all standard bedside techniques.

Murmurs originating within the right-sided chambers of the heart were best differentiated from all other murmurs by:

The murmur of hypertrophic cardiomyopathy was distinguished from all other murmurs by:

The murmurs of mitral regurgitation and ventricular septal defect had parallel responses to all maneuvers, but could be differentiated from other systolic murmurs by:

No single maneuver identified the murmur of aortic stenosis, but the diagnosis could be made by exclusion. Although no single maneuver is 100 percent accurate in diagnosing the cause of a systolic murmur, its origin can be determined accurately at the bedside by observation of the response to a combination of maneuvers.

J Cardiol 1988 Jun;18(2):415-23
Phonocardiographic and two-dimensional and pulsed Doppler echocardiographic studies of Still's murmurs
Suzuki J, Sakamoto T, Hada Y, Amano K, Takahashi H, Hasegawa I, Sugimoto T.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo.

The prevalence of Still's murmur was examined by phonocardiographic study, and the clinical significance of this murmur was investigated using pharmacodynamic phonocardiography and echocardiography. Still's murmur was present in 224 of 9,478 cases (2.4%) in school children. Its prevalence was 143 in 4,524 (3.2%) in elementary school children and this was significantly greater than that in middle school youngsters who numbered 81 among 4,954 (1.6%) (p less than 0.001). There were neither abnormal findings on two-dimensional echocardiography, nor pathological regurgitant signals on pulsed Doppler examination. After the inhalation of amyl nitrite, Still's murmur was accentuated by 5.3 +/- 3.0 dB, and was louder in the expiratory than in the inspiratory phase by 4.7 +/- 3.5 dB.

J Cardiol 1987 Sep;17(3):475-87
Musical systolic murmur produced by oscillation of the systolic anterior motion of the mitral apparatus: relation to the genesis of Still's murmur
Kagawa T, Fukuda N, Irahara K, Kawano K, Okumoto T, Tominaga T, Uchida T, Kawano T, Oki T, Mori H.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokushima.

The genesis of a musical systolic murmur produced by systolic anterior motion (SAM) of the mitral apparatus was investigated in four patients using phonocardiography and echocardiography. Two patients (Case 1 and 3) had hypertrophic cardiomyopathy (one, the obstructive type; the other, the nonobstructive type) and the remaining two (Case 2 and 4) had redundant chordae tendineae. 1. In every patient, regular oscillation of the SAM was observed, coinciding in time with the musical systolic murmur, which was simultaneously recorded. The fundamental frequency of the musical systolic murmur was recorded as integrally multiplied numbers of the SAM. Such regular oscillation was not observed in the echograms of other cardiac structures. In a patient with hypertrophic obstructive cardiomyopathy (Case 1), both the amplitude and oscillation of the SAM were increased by amyl nitrite inhalation, and were decreased by angiotensin II infusion. Correspondingly, the intensity of the musical murmur showed similar reaction. No findings suggestive of mitral valve prolapse or mitral regurgitation were found in any patients. Therefore, the oscillation of the SAM produced by blood ejected from the left ventricle was considered the source of the musical systolic murmur in these patients. 2. Two patients with redundant chordae tendineae had no clinical abnormalities except for chordal redundancy; therefore, the musical murmur in these cases was considered to be functional. Particularly, one of them was compatible in character with the so-called Still's murmur. In conclusion, the regular oscillation of the SAM may be the source of the musical systolic murmur, and they must be taken into consideration as part of the genesis of Still's murmur.

Arch Inst Cardiol Mex 1987 Mar-Apr;57(2):151-4
Differentiation of ejection systolic and regurgitant murmurs with inhaled isoproterenol
Sanchez S, Meaney E, Enriquez J, Rodriguez T, Lepe V.

A common clinical problem is the differentiation among ejection and regurgitant murmurs. Inhalation of amyl nitrite is useful for this purpose because it increases the intensity of ejection murmurs while decreases that of regurgitant ones. Because amyl nitrite is not easily available, inhaled isoproterenol was tested in seventeen patients with ejection murmurs and eighteen with regurgitant ones. Isoproterenol was administered at doses of 480-640 mcg, according to age and corpulence. The changes in murmur amplitude and heart rate were phonocardiographically registered immediately and then every 15'' up to a minute and a half after the inhalation, and were expressed as percent of change with respect to basal values. Heart rate increased in both groups. The intensity of ejection murmurs increased immediately and maximally 45'' after inhalation; on the contrary, the intensity of regurgitant murmurs decreased immediately and maximally 15'' after inhalation. It is concluded that isoproterenol, whose effects are similar to those of amyl nitrite, can substitute the latter in the clinical and phonocardiographically differentiation of systolic murmurs.

J Cardiogr 1986 Dec;16(4):977-86
Power spectrum of heart murmurs: special reference to mitral regurgitant murmurs
Mori T, Ohnishi N, Sekioka K, Nakano T, Takezawa H.
First Department of Internal Medicine, Mie University School of Medicine.

Heart murmurs, especially the mitral regurgitant murmurs of 40 patients were analyzed using the fast Fourier transformation technique. 1. Three types of frequency spectral pattern of mitral regurgitation (MR) were demonstrated: A) broad, spanning 100 to 500 Hz, B) narrow, characterized by one giant peak, and C) two peaks. The reason for these patterns was not clear, but they may be related to various hemodynamic events. 2. The mean frequency (f) in MR was 295 +/- 38 Hz and it increased in proportion to the regurgitant grade: e.g., Sellers II, 258 +/- 27 Hz; Sellers III, 294 +/- 23 Hz; and Sellers IV, 311 +/- 65 Hz. The accumulated percentage of the 200-400 Hz component decreased, while that of the 400-600 Hz component increased. 3. The f in MR of various etiologies were as follows: It was higher in ruptured chordae tendineae, rheumatic cases and mitral valve prolapse syndrome, but was lower in papillary muscle dysfunction and dilated cardiomyopathy. In the latter two, the percentage of the 0-200 Hz component was greater than in other disorders. The degree of left ventricular dysfunction and of myocardial injury may be responsible for the changes in the propagation properties. In ventricular septal defect and aortic stenosis, the f was 306 +/- 12 Hz and 230 +/- 40 Hz, respectively. The frequency spectrum of the latter was lower than that of MR, which may be derived from the difference between ejection and regurgitant murmurs; whereas, that of ventricular septal defect was similar to that of rheumatic MR. 4. The relation between the frequency spectrum and the phase of systole was studied. In dilated cardiomyopathy and papillary muscle dysfunction, the f of each phase increased in late systole; whereas, the maximum f was in mid-systole in other disorders. 5. Administration of amyl nitrite resulted in a decreased f, an increased percentage of the 0-200 Hz component, and a decreased 400-600 Hz component. The spectral distribution shifted to the lower frequency region. Results of this study suggested that significant information can be obtained from the frequency analysis of heart murmurs.

J Cardiogr 1986 Dec;16(4):1013-25
SAM sound studied by pulsed Doppler echocardiography
Tanigawa N, Ozawa Y, Nagasawa M, Kojima R, Jinno K, Komaki K, Hatano M.
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo.

The occurrence of a systolic sound in hypertrophic obstructive cardiomyopathy (HOCM) has been well known for more than 20 years. This was phonoechocardiographically regarded as the sound coincident with the abrupt halt of the systolic anterior movement (SAM) of the mitral valve echo, and it has been termed the SAM sound. A 58-year-old man with HOCM was admitted with right hemiplegia. He was found to have a SAM sound which waxed and waned in intensity, and at times moved earlier into systole. He was studied by cardiac catheterization, M-mode and two-dimensional Doppler echocardiography (pulsed, continuous wave and color flow Doppler methods). Asymmetric septal hypertrophy (interventricular septal thickness = 25 mm, left ventricular posterior wall thickness = 14 mm), as well as SAM and midsystolic aortic valve closure were demonstrated. The presence and intensity of the sound was not related to rhythm (normal sinus rhythm vs atrial flutter), heart rate, respiration, position, or inhalation of amyl nitrite. Two-dimensional Doppler echocardiography revealed the following: 1. In the left ventricular outflow tract just below the aortic valve, a systolic turbulent flow was always present. 2. In the left ventricular chamber near the apex, a systolic laminar flow was interrupted in those cycles where the SAM sound was present. Otherwise, in cycles lacking the SAM sound, laminar flow in this locality continued throughout systole (even shorter duration than normal). 3. In the left ventricular inflow tract, diastolic flow was unaffected by the presence of the sound. 4. No mitral regurgitation was observed using color flow Doppler echocardiography. In summary, a SAM sound appeared to be associated with sudden deceleration of blood flow from the apex to the mid left ventricle.

Ann Intern Med 1986 Sep;105(3):368-70
Diagnosis of left-sided regurgitant murmurs by transient arterial occlusion: a new maneuver using blood pressure cuffs.
Lembo NJ, Dell'Italia LJ, Crawford MH, O'Rourke RA.

Transient arterial occlusion of both arms with blood pressure cuffs inflated to 20 to 40 mm Hg above systolic pressure for 20 seconds augmented the intensity of left-sided regurgitant murmurs caused by aortic regurgitation, mitral regurgitation, and ventricular septal defect. We compared this new maneuver with handgrip exercise, squatting, and amyl nitrite inhalation in 30 patients with left-sided regurgitant murmurs and in 30 patients with murmurs not caused by left-sided regurgitation. Transient arterial occlusion increased the intensity of left-sided regurgitant murmurs more than squatting (p = 0.02) and did not statistically differ from isometric handgrip exercise and amyl nitrite inhalation in ability to identify the presence of these murmurs. A false-positive diagnosis of left-sided regurgitant murmur was less likely when using transient arterial occlusion than when using handgrip exercise (p = 0.05) and squatting (p less than 0.001). Thus, transient arterial occlusion works as well as or better than other standard bedside maneuvers for diagnosing or excluding left-sided regurgitant murmurs and can be applied to all patients.

J Cardiogr 1985 Dec;15(4):1071-85
Apical mid-diastolic rumble in hypertrophic cardiomyopathy: a pulsed Doppler echocardiographic study
Tominaga T, Oki T, Ohkushi H, Ishimoto T, Taoka M, Fukuda N, Mikawa T, Irahara K, Niki T, Mori H.

To investigate the mechanism of an apical mid-diastolic rumble in hypertrophic cardiomyopathy (HCM), we recorded left ventricular (LV) inflow velocity patterns using pulsed Doppler echocardiography and apexcardiography for 10 HCM patients with rumble and 20 HCM patients without rumble. Controls consist of 17 normal subjects, three patients with complete atrioventricular block and two patients with artificial right ventricular pacemakers. The LV inflow velocity profiles were analyzed in terms of acceleration time (AT) and deceleration time (DT) of the rapid filling wave, and the ratio of peak velocity of the atrial contraction wave to that of the rapid filling wave (A/D ratio). The results were as follows: The apical mid-diastolic murmur in HCM had a crescendo- decrescendo character mainly of medium frequency, and increased in intensity after the inhalation of amyl nitrite. All patients with rumble had asymmetric septal hypertrophy and the five of these had LV outflow obstruction. In six of the 10 patients with rumble, mild mitral regurgitation was detected. In HCM with rumble, the AT tended to be shorter than that of HCM without rumble, but it was significantly longer than the AT of normal subjects. In HCM with rumble, the DT was significantly shorter than that of HCM without rumble, but it was significantly longer than the DT of normal subjects. There was no significant difference in the A/D ratio between the HCM with rumble and the normal subjects, but the A/H ratio of the apexcardiogram was significantly increased in HCM with rumble as compared with those of HCM without rumble and of the normal subjects. The LV dimension was significantly decreased in HCM with rumble as compared with those of HCM without rumble and the normal subjects. Peak negative VCF was significantly decreased in HCM with rumble as compared with that of HCM without rumble. But there was no significant difference in this parameter between HCM with rumble and the normal subjects. In simultaneous recordings of apical mid-diastolic rumble and LV inflow velocity patterns, the rumble appeared to start after the beginning of the diastolic rapid filling wave and to stop before or at the end of the diastolic rapid filling wave. In patients with complete atrioventricular block and with artificial right ventricular pacemakers, the apical mid-diastolic rumble appeared when the P wave was during the rapid filling phase of the left ventricle.

J Cardiogr 1985 Mar;15(1):197-205
An intermittent mid-diastolic musical murmur indicating aortic regurgitation: report of a case
Inanami H, Asaka T, Yoshida K, Takagi Y, Okumachi F, Yanagihara K, Kato H, Yoshikawa J.

An unusual mid-diastolic musical murmur developed soon after cardiac catheterization of a 55-year-old man with mitral stenosis. His physical findings consisted of an accentuated first heart sound, an opening snap and a grade 3/6 mid-diastolic rumbling murmur. No early diastolic murmur was audible. However, soon after cardiac catheterization, a mid-diastolic "cooing" murmur at a frequency of 200 cycles/sec developed. This murmur resolved with the patient in the sitting position, or by leg raising. With Valsalva or Muller maneuvers this murmur was abolished transiently, and it disappeared on administering either amyl nitrite or methoxamine. Echocardiography revealed early diastolic vibrations in the aortic valve. Pulsed Doppler echocardiograms revealed harmonic signals of the aortic cusp at a fundamental frequency of 200 cycles/sec. These harmonic signals could be recorded only in mid-diastole. The frequency patterns of the murmur and the Doppler signals were identical; therefore, the murmur was judged to be produced by aortic valve vibrations. Furthermore, resonance of cardiac structures which accentuate the murmur might be related to the occurrence of this murmur. Pulsed Doppler echocardiography is helpful in identifying the site of origin of this musical murmur.

Am J Cardiol 1984 Jul 1;54(1):79-83
Significant coronary artery disease detected by amyl nitrite and systolic time intervals.
Mitake H, Sawayama T, Nezuo S, Fuseno H, Samukawa M, Hasegawa K, Harada Y.

The relation between changes in left ventricular systolic time intervals with amyl nitrite (AN) inhalation and the severity of coronary artery disease (CAD) was evaluated in 77 patients who underwent catheterization because of chest pain. In 25 subjects with normal coronary angiograms (control group), AN inhalation increased the ejection time (ET), shortened the preejection period (PEP) and increased the ET/PEP markedly. In the 52 patients with CAD (CAD group), the ET/PEP changed insignificantly after AN. The difference between the 2 groups was significant (p less than 0.001). At cardiac catheterization, the increase of left ventricular dP/dt after AN in the control group was significantly larger than that in the CAD group. Although a positive correlation between changes in ET/PEP with AN and ejection fraction at rest was noted in patients with 1-vessel CAD, no such correlation was noted in those with multivessel CAD. This suggests that factors in addition to pump function, such as the degree of CAD, influence the effect of AN inhalation on systolic time intervals. When an increase of less than 30% in ET/PEP occurs with AN inhalation, the presence of significant CAD can be detected with a sensitivity of 92%, a specificity of 84% and the predictive value of 92%. The AN inhalation test is safe and simple, and thus could serve as a stress test for evaluating the presence and severity of significant CAD.

Angiology 1984 Feb;35(2):115-21
Pulsus alternans. Its response to amyl nitrite inhalation.
Cheng TO, Leet CJ.

Marked pulsus alternans was observed in a patient with primary congestive cardiomyopathy. Afterload reduction with amyl nitrite caused the disappearance of the pulsus alternans. Investigation by phonocardiography, echocardiography, systolic time interval measurement and cardiac catheterization disclosed that during pulsus alternans the weak beat originated following a short diastolic filling period and generated much lower contractile force. This report may be relevant to the currently accepted concepts of afterload reduction in the treatment of chronic congestive heart failure.

J Med 1984;15(3):227-32
Mitral systolic honk in a case of congenitally corrected transposition of the great vessels.
Iarussi D, Gualtieri S, Pisacane C, Iacono A.
A woman suffering from TCGV associated with steno-insufficiency with a prolapse of left atrioventricular valve (tricuspid) and an insufficiency with a prolapse of right atrioventricular valve (mitral) presented a systolic honk which was to be registered in all the precordial area. The increase of this noise at the end of inspiration and after amyl nitrite, in the absence of any relevant change as to the prolapse of both atrioventricular valves, demonstrated that the honk originated from the right atrioventricular valve more than from the left one.

J Cardiogr 1982 Dec;12(4):915-28
Amyl nitrite test in the evaluation of left ventricular function: application to ischemic heart disease and Duchenne's progressive muscular dystrophy
Honda M, Fukuda K, Miyazaki A, Nishimoto Y, Shimoura K, Shukuya M, Masuda Y, Inagaki Y, Muraki N, Hirai A.

The effect of amyl nitrite (AN) inhalation on the left ventricular function was evaluated by mechanocardiography and echocardiography. The patient's group consisted of 110 cases with ischemic heart disease (IHD) and 25 cases of dystrophia musculorum progressiva (DMP) of Duchenne type. The former was a representative of impairment of blood supply and myocardial involvement, and the latter was of predominant myocardial disease. The control was age-matched 32 normals for IHD group and 17 cases for DMP group. Left ventricular function was mainly evaluated by systolic time intervals (STI) and the echocardiographic correlates. Fifty-five cases of IHD group were tested by coronary angiography and left ventriculography and these data were compared with the noninvasive measures. The results were as follows: I. IHD group: The ratio of ejection time (ET) to pre-ejection period (PEP), ET/PEP, did not change so much as in controls after AN inhalation, and this percent change was much smaller in cases with lesions of the left anterior descending artery (LAD) than in cases with lesions of the right coronary artery (RCA). On the other hand, mean posterior wall velocity (mPWV) and posterior wall excursion (PWE) changed greater in patients with LAD lesion than in those with RCA lesion. In cases with LAD stenosis, percent change in ET/PEP was smaller in cases with asynergy than in cases without it, disclosing more significant impairment of the left ventricle in the former. II. DMP group: In severe cases, ET/PEP was small even at rest, and percent change by AN inhalation was smaller than control in mild cases and smallest in severe cases. This seems to be useful in evaluating the severity of the diseased process. The mPWV and PWE showed impairment of left ventricular motion even at rest, but it was clearly showed in severe cases after AN inhalation. These results indicate that impairment of left ventricular function induces the poor response to AN inhalation and this, in turn, results in the lack of hyperactivity of the heart produced by this drug.

Chest 1982 Aug;82(2):158-63
Mitral valve prolapse. Cross sectional and provocative M-mode echocardiography.
Noble LM, Dabestani A, Child JS, Krivokapich J.

False-negative supine M-mode echocardiograms occur in some patients with proved mitral valve prolapse. To investigate further, we performed M-mode echocardiography (MME) during standing and after the inhalation of amyl nitrite in 17 patients (group 1) selected for auscultatory evidence of mitral valve prolapse (MVP) but negative supine MME. To validate the standing MME technique, eight patients with classic auscultatory MVP with positive supine MME for MVP (group 2) and 15 control subjects (group 3) were studied. Supine cross-sectional echocardiography (CSE) was compared to MME in all three groups. Standing MME elicited echocardiographic evidence of MVP in 14/17 (82 percent) of group 1--auscultatory evidence of MVP but negative supine MME; CSE demonstrated MVP in 8/13 (62 per cent) of the same patients. There was no clear advantage of the CSE long axis view over the CSE apical four chamber view in the diagnosis of MVP in these selected subjects; however, the two views were complementary. Amyl nitrite was ineffective in eliciting echocardiographic evidence of MVP.

Chest 1982 Apr;81(4):483-7
The effect of amyl nitrite on the mitral valve echocardiogram in presumably healthy young adults.
Morise AP, Gibson TC, Davis SM, Bonazinga BJ, Sbarbaro JA.

We analyzed the use of amyl nitrite as a provocative factor in the diagnosis of mitral valve prolapse in a population of healthy young adults. Sixty-five men and 11 women underwent continuous M-mode echocardiographic and phonocardiographic monitoring before, during and after the administration of inhaled amyl nitrite. All of the 76 subjects had normal baseline echocardiograms, and all had a satisfactory hemodynamic response to amyl nitrite. Mitral valve prolapse, defined by echocardiography and phonocardiography, was not provoked in any of the subjects. Therefore, we concluded that, although this technique may be difficult, significant false-positive results should not occur if adherence to strict diagnostic criteria takes place.

Arch Inst Cardiol Mex 1982 Mar-Apr;52(2):103-11
Phonomechanocardiographic study of innocent murmurs in children
Esquivel Avila J, Veloz Nunez ML, Aldana Herrero A, Hernandez Martinez G.

At the National Institute of Pediatrics DIF (formerly IMAN), a comparative study was performed in 157 healthy children. Ninety four (59.8%), had an innocent cardiac murmur, and 63 children (40.1%) had no heart murmur detectable. The presence of innocent murmurs was more frequent in pre-school and school age; murmurs of basal location were predominant. The murmurs were brief midsystolic and of the ejective type. All of them had the characteristics of a vibratory murmur of sinusoidal type, with diagonal radiation and low frequency. One more dynamic of pharmacological tests were performed in 60 children. In 88.5% of the cases, the murmur showed left behavior during the Valsalva monouver. Only in 15.7% during the Azoulay maneuver suggested right origin of the murmur. In 70% the murmur decreased with orthostatism and in the children who inhaled amyl nitrite, the murmur showed a behavior suggestive of aortic ejective origin. The comparison between the groups with and without murmurs showed that the heart rate was lower for those children with murmurs (P less than 0.05), the left ventricle ejection time was shorter in children with murmurs (P less than 0.01), but instead the preejection period was longer in children with murmurs (P less than 0.05). These differences let us point out that in children with murmurs the blood flow during the early systole is higher than in those without murmurs. This conditions probably a determinant in the origin of the innocent murmur.

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