Catheterization and Cardiovascular Interventions 00:00–00 (2015)
Hemodynamic Rounds The Role of Hemodynamic Catheterization in the Evaluation of Hypertrophic Obstructive Cardiomyopathy: A Case Series Kalkidan Bishu,1* MD, MS, Megan Coylewright,2 MD, MPH, and Rick Nishimura,3 MD Confirmation of the presence and magnitude of left ventricular outflow tract (LVOT) obstruction is a critical component of the evaluation of symptoms in patients with hypertrophic cardiomyopathy (HCM). The presence of LVOT obstruction in patients with severe symptoms refractory to pharmacologic therapy identifies a subgroup of HCM patients who may benefit from septal reduction therapy. Two-dimensional echocardiography with continuous wave Doppler is the main tool for confirming the presence and severity of LVOT obstruction in HCM. However, when uncertainty remains following non-invasive evaluation, invasive hemodynamics studies are required to confirm and quantify LVOT obstruction. In this manuscript we describe a series of 6 cases in which hemodynamic catheterization is instrumental in supplementing non-invasive imaging in the assessment of LVOT obstruction in HCM. VC 2015 Wiley Periodicals, Inc. Key words: cardiomyopathy; hypertrophic; catheterization; diagnostic; catheterization; transeptal; hemodynamics
INTRODUCTION
Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease characterized by thickening of the left ventricular wall in the absence of other cardiac or systemic diseases, affecting up to 0.2% of the general population [1]. Two-thirds of patients with HCM have a dynamic left ventricular outflow tract (LVOT) obstruction due to a mechanical impediment to blood flow caused by systolic anterior motion (SAM) of the mitral valve [2]. Confirmation of the presence, magnitude and location of obstruction in HCM is critical in the evaluation of patients with HCM because obstruction mediates the development of severe heart failure symptoms [3,4], impacts long term outcomes [5], and is the primary target for therapy [6]. Transthoracic echocardiography (TTE) with continuous wave Doppler is the principal diagnostic modality for determining the presence and magnitude of LVOT obstruction in HCM [7]. Direct visualization of SAM of the mitral valve contacting an area of septal hypertrophy in combination with a late peaking systolic velocity obtained by continuous wave Doppler across the outflow tract is necessary for the diagnosis of C 2015 Wiley Periodicals, Inc. V
subvalvular obstruction. The severity of obstruction can be obtained by applying the modified Bernoulli equation to the peak systolic Doppler outflow velocity [8]. Severe resting obstruction is present if the LVOT Additional Supporting Information may be found in the online version of this article. 1
Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado 2 Section of Cardiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 3 Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota Conflict of interest: Nothing to report. *Correspondence to: Kalkidan Bishu, M.D., M.S., Fellow in Interventional Cardiology, Department of Medicine, University of Colorado School of Medicine 12401 E. 17th Ave., #524, Aurora, CO 80045. E-mail: [email protected] Received 26 July 2014; Revision accepted 18 January 2015 DOI: 10.1002/ccd.25856 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com)
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Fig. 1. Catheter entrapment when LV outflow tract gradient is assessed using a retrograde approach. A. Pressure tracings from the LV inflow tract (LV) measured via a transseptal approach and the ascending aorta (Asc Ao) with no significant gradient B. Pressure tracings from the LV measured via a retrograde approach and the ascending aorta (Asc Ao) inaccurately demonstrating a gradient of 120 mm Hg in the absence of a spike and dome configuration of the aortic waveform confirming catheter entrapment.
gradient is >50 mm Hg. If no obstruction is detected at rest, provocative tests such as the Valsalva maneuver, exercise, or the use of inhaled amyl nitrite may bring out a latent obstruction [2,6,9]. One-third of patients with HCM have resting LVOT obstruction and an additional one-third may have LVOT obstruction with provocation [2]. Septal reduction therapy is indicated only for severely symptomatic patients who are intractable to optimal medical therapy and who are demonstrated to have severe obstruction [7]. Although determining the presence and magnitude of LVOT obstruction by noninvasive TTE is possible in the majority of patients, invasive hemodynamic catheterization may be required in a subset due to several reasons. First, in patients with no resting gradient, provocative maneuvers are required to elicit a latent obstruction, which may be difficult to capture with Doppler echocardiography, including during exercise [10]. The dynamic nature of obstruction in HCM can further confound the difficulty of capturing a transient gradient using Doppler echocardiography [11]. Second, contamination of the LVOT velocity Doppler signals may arise from a higher velocity mitral regurgitation (MR) signal, thus limiting accurate assessment of the gradient. Third, dynamic LVOT obstruction may
coexist with a fixed valvular aortic stenosis or subvalvular stenosis. Delineation of the contribution from dynamic LVOT obstruction is difficult given that assumptions for the modified Bernoulli equation traditionally used to estimate pressure gradients are invalid with obstruction in series [8,12–14]. Finally, latepeaking systolic signals upon Doppler interrogation can be generated by complete cavity obliteration from a hypercontractile LV, simulating LVOT obstruction [15]. The location of obstruction (outflow versus midventricle) may be difficult to determine by continuous wave Doppler echocardiography, which samples all velocities across the Doppler beam. In this case series, we illustrate the utility of hemodynamic catheterization as a complementary tool to echocardiography in helping establish the presence, magnitude and location of obstruction in patients with HCM. We wish to emphasize that the hemodynamic evaluation of patients with HCM takes a systematic approach as well as meticulous attention to detail. For identification of LVOT obstruction, we used a transseptal approach to measure the LV pressure from the LV inflow as described by Wigle et al. [16,17]. with simultaneous central aortic pressures. This avoids the potential problem of catheter entrapment, which can occur in the small hypertrophied ventricles and hyperdynamic contractility resulting in cavity obliteration, when using catheters from a retrograde aortic approach (Fig. 1). The placement of the catheter from a retrograde approach is usually in the lateral aspect of the mid-ventricle where catheter entrapment can occur. The transseptal approach may not be necessary in many patients in whom a retrograde approach would be adequate but is a reliable method to avoid entrapment when there is an important clinical question to be answered regarding the presence, severity, and location of the gradient. If a retrograde approach is taken, either an end-hole catheter or a catheter with an end hole and limited distal side holes should be used. In some institutions a properly calibrated and equalized pressure wire is used for measurement of LV pressure. Transseptal catheterizations should only be performed by operators who are highly experienced in this technique. CASE SERIES Case 1: Absence of Severe Resting Gradient
A 70-year-old woman presented with exertional shortness of breath for the past 2 years, already treated with low dose beta blocker for presumed HCM. On physical examination she had a soft grade 2/6 systolic ejection murmur at the left sternal border with a minimal increase with the squat-to-stand maneuver. TTE showed asymmetric hypertrophy of the basal
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Fig. 2. Use of isoproterenol to demonstrate latent left ventricular outflow tract (LVOT) obstruction. A. Pressure tracings from the ascending aorta (Asc Ao), LV inflow tract and left atrium (LA) demonstrating no LVOT gradient at rest. B. Pressure tracings from the Asc Ao, LV inflow tract and LA after intravenous administration of isoproterenol at 2 mcg min21 showing the development of a 90 mm Hg gradient in the LVOT.
interventricular septum with a resting LVOT gradient of 27 mm Hg. Doppler interrogation of the LVOT with Valsalva did not produce a clear signal to help identify a latent obstruction. It was unclear as to whether the etiology of her symptoms was due to more dynamic outflow obstruction, diastolic dysfunction or a noncardiac etiology. Thus further evaluation was pursued with a hemodynamic catheterization. On catheterization, there was no LVOT gradient at rest (Fig. 2A). However, following the administration of intravenous isoproterenol at 2 mcg min1 (Fig. 2B), a 90 mm Hg LVOT gradient was demonstrated. Her medical therapy was optimized with uptitration of beta blockers and her symptoms improved. The mean left atrial pressure was normal at less than 12 mmHg at rest and during provocation, ruling out diastolic dysfunction as an etiology of her symptoms. Discussion When there is no resting gradient, interventions such as the Valsalva maneuver, inhaled amyl nitrite or exercise may provoke a gradient that can be documented by TTE. Valsalva and amyl nitrite inhalation work similarly by reducing preload, which leads to an increase in the LVOT gradient [18]. Exercise testing, in which the gradient is measured during or immediately after bicycle or treadmill exercise, can also be
combined with Doppler echocardiography to determine the presence of a physiologically provocable LVOT gradient [7]. Elevated gradients are seen in response to increases in contractility and reduction in afterload. However, rapid respiratory movements during exercise may potentially interfere with Doppler interrogation of the LVOT [10]. Dobutamine infusion is not a recommended method to look for a provocable gradient [7]. Dobutamine increases myocardial contractility and heart rate via b1 receptors in the heart, but also increases total peripheral resistance and thus afterload via activation of a1 receptors [19]; this combination of effects counter one another in HCM. In addition, dobutamine may lead to cavity obliteration in patients with small, hypertrophied ventricles and cause an increased velocity not related to LVOT obstruction. Isoproterenol decreases total peripheral vascular resistance through its binding of b2 skeletal muscle smooth muscle receptors, decreases preload by binding venous b receptors and increases myocardial contractility and heart rate via b1 receptors leading to increased dynamic LVOT obstruction and a measurable gradient [19–21]. In an elegant early study, Braunwald et al. demonstrated a decrease in cardiac output, fall in systemic arterial pressure and an increase in left ventricular systolic pressure with intravenous administration of isoproterenol [22]. These hemodynamic changes were
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Fig. 3. LVOT Doppler contamination by a mitral regurgitation jet. A. Doppler echocardiographic interrogation of the left ventricular outflow tract (LVOT) after amyl nitrite inhalation shows a high-velocity, late-peaking signal with a contour that is atypical for LVOT obstruction and concerning for contamination from mitral regurgitation. B. Pressure tracings from ascending aorta (Asc Ao) and LV inflow tract demonstrating a 50 mm Hg gradient across the LVOT. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
also noted in patients with no LVOT gradient at baseline, illustrating the potential role of isoproterenol in subjects with latent obstruction [22–24]. Isoproterenol is typically used in the catheterization laboratory where invasive monitoring and rapid resuscitation is available. Intravenous infusion of isoproterenol or other inotropes such as norepinephrine may produce a gradient between the LV and aorta in dogs with LVH, normal human patients, or human patients with LVH without true LVOT obstruction [24–26]. The mechanism is multifactorial but may be (1) related to catheter entrapment or (2) early rapid and complete early ejection with cavity obliteration during late systole [27,28]. Outflow gradients can also be induced in normal ventricles during isoproterenol infusion due to an increase
in the inertial dynamics of LV ejection [26]. Transseptal catheterization will avoid entrapment in this scenario and integration of all clinical data including TTE evaluation for SAM of mitral leaflets that is easily performed during pharmacologic intervention in the catheterization lab will help distinguish other causes of a gradient from true LVOT obstruction. Thus, in selected patients in whom there is a high degree of suspicion that LVOT obstruction is responsible for drug refractory symptoms, pharmacologic provocation during hemodynamic catheterization may establish the presence of an inducible gradient. The simultaneous measurement of LV filling pressures may also be helpful to rule out diastolic dysfunction as an etiology of symptoms.
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Fig. 4. Secondary mitral regurgitation due to dynamic LVOT obstruction. A. Pressure tracings from ascending aorta (Asc Ao), LV inflow tract and left atrium (LA) at rest showing severe left ventricular outflow tract (LVOT) obstruction characterized by a spike and dome pattern in the Asc Ao and a 100 mm Hg gradient across the LVOT. LA pressure tracings showed a
large V wave consistent with severe mitral regurgitation shown in Supporting Information Movie 1. B. Pressure tracings from Asc Ao and LV inflow tract and LA after the administration of phenylephrine at 2 mcg kg21 min21 showing that the LVOT gradient and large V wave in the LA are gone, and the Asc Ao pressure contour has normalized.
Case 2: Contamination of LVOT Doppler Signal by MR Jet
regurgitation velocity was 5 m sec1 indicating the gradient between the left atrium and the LV was 100 mm Hg (estimated from the modified Bernoulli formula, gradient ¼ 4 V2, where V is the peak systolic velocity of Doppler flow signal). Of note, with an elevated LV systolic pressure of 160 mm Hg, the patient also had markedly elevated left atrial filling pressures. The patient underwent alcohol septal ablation and reported improvement in exertional symptoms on follow-up.
A 77-year-old man presented with symptoms of exertional chest pain and shortness of breath after walking less than 20 feet or when climbing a single flight of stairs. He was on maximally tolerated beta blocker and calcium channel blocker therapy. Physical examination revealed a soft systolic murmur that increased with the squat-to-stand maneuver. Coronary angiography showed no obstructive lesions. His TTE showed LV hypertrophy with prominent basal septum involvement. There was SAM of the mitral valve leaflet with mild, posteriorly directed regurgitation at rest, as well as with Valsalva and amyl nitrite administration. However, it was difficult to obtain the true LVOT signal on Doppler interrogation due to contamination of the signal by the MR jet. Given a lack of clarity regarding a benefit from septal reduction therapy, the patient proceeded to hemodynamic catheterization. This demonstrated a 50 mm Hg gradient between the LVOT and the ascending aorta, while the Doppler signal of nearly 5 m sec1 suggested a gradient of 100 mm Hg (modified Bernoulli equation ¼ 4 V2) [8]. Thus, the Doppler signal was shown to be representative of the mitral regurgitant jet during systole, approximating the gradient between LV systolic pressure and LA (Fig. 3A and B). Peak mitral
Discussion
LVOT obstruction is identified as a high-velocity, late-peaking concave signal on continuous wave Doppler associated with SAM of the mitral valve leaflet on 2D echocardiography. The modified Bernoulli equation is applied to the peak instantaneous velocity across the LVOT to calculate the maximum gradient [8]. However, as shown in this patient, high-velocity MR jets may contaminate the late-peaking signal or be misidentified as an LVOT signal [15]. This scenario requires invasive hemodynamic catheterization. We were able to accurately measure the gradient between the LV inflow tract and ascending aorta using a catheter placed in the LV inflow tract via a transseptal puncture and a second side-hole catheter placed in the aortic root in a retrograde fashion [16,17].
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Fig. 5. Serial stenoses. A. Pressure tracings from ascending aorta (Asc Ao) and left ventricular (LV) inflow tract demonstrating a 120 mm Hg gradient in the left ventricular outflow tract (LVOT). B. When the catheter in the LV inflow tract is advanced to the LVOT just under the aortic valve leaflets, a smaller pressure gradient across the aortic valve of 20 mm Hg remains. C. A 100 mm Hg gradient between the LV inflow
tract and catheter placed in LVOT just under the aortic valve. D. Following administration of phenylephrine at 1 mcg kg21 min21, there is higher pressure in the Asc Ao. The gradient between the LV inflow and the Asc Ao decreased to 30 mm Hg indicating a significant dynamic LVOT obstruction with only moderate aortic valve stenosis.
Case 3: Increasing Afterload to Distinguish Dynamic, Secondary MR From Primary MR A 69-year-old woman presented with a history of persistent dyspnea climbing stairs for the past 5 years. Despite talc pleurodesis for a transudative left pleural effusion and an atrial fibrillation ablation, she had no improvement in symptoms. On physical examination, she had a harsh grade 2/6 mid-peaking systolic ejection murmur at the left sternal border that ended before the second heart sound. This murmur increased with the squat-to-stand and Valsalva maneuvers. She had a separate, grade 2/6 holosystolic murmur at the cardiac apex. TTE showed LV hypertrophy with asymmetric septal involvement and a heavily calcified mitral annulus with significant MR which was inadequately graded. The patient was referred for evaluation for septal reduction therapy. However, it was not clear if she needed septal myectomy with mitral valve surgery or solely septal reduction therapy (via either septal myectomy or alcohol septal ablation). During cardiac catheterization, there was a resting LVOT gradient of 100 mm Hg (Fig. 4A) and severe MR (Supporting Information Movie 1). Following the administration of phenylephrine at 2 mcg kg1 min1, the LVOT gradient was abolished (Fig. 4B) and MR was only mild (Supporting Information Movie 2) indicating the MR was secondary to SAM and associated with dynamic LVOT obstruction. The patient underwent
septal myectomy and was able to exercise daily without limitations.
Discussion Mitral regurgitation in HCM is predominantly functional and related to SAM. The dynamic nature of MR in HCM can be demonstrated by changes in the severity of the MR on physical examination as its severity increases with maneuvers that worsen LVOT obstruction (Valsalva and squat-to-stand maneuvers). Pharmacologic interventions that increase afterload reduce dynamic MR due to SAM and in turn, lower the LVOT gradient, while interventions that worsen MR by reducing afterload (inotropic agents or vasodilators) increase the degree of obstruction [29,30]. A progressive increase in afterload can be induced pharmacologically by using peripheral a1 receptor agonists such as methoxamine or phenylephrine to suppress dynamic LVOT obstruction [20,22]. Both methoxamine and phenylephrine are direct-acting a1 receptor agonists that increase total peripheral resistance by causing vasoconstriction in cutaneous, splanchnic, renal and skeletal circulation, and decrease heart rate in a vagally mediated reflex [19] leading to a reduction in SAM of the mitral leaflets and a demonstrably lower LVOT obstruction [29,30]. Braunwald et al. demonstrated that intravenous methoxamine abolishes the resting LVOT
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obstruction of aortic valve stenosis versus dynamic left ventricular outflow obstruction. If the former, surgical intervention with aortic valve replacement would be pursued prior to noncardiac surgery. On hemodynamic catheterization, a gradient between the LV inflow tract and ascending aorta of 120 mmHg was measured (Fig. 5A). A gradient of 20 mm Hg was measured between the ascending aorta and a catheter placed immediately below the aortic valve in the LV outflow tract (Fig. 5B) indicating the LVOT gradient was 100 mm Hg (seen in Fig. 5C). Following the administration of phenylephrine at 1 mcg kg1 min1, the gradient between the LV inflow tract and ascending aorta decreased to 30 mmHg (Fig. 5D). These findings were consistent with a prominent contribution of dynamic subvalvular LVOT obstruction rather than severe aortic stenosis. She was placed on maximal beta blocker therapy and underwent successful left hip replacement surgery.
Fig. 6. Obstruction at apical pouch. A gradient exists between the apical pouch and LV inflow tract, but not between the LV inflow and ascending aorta (Asc Ao) indicating a lack of LVOT gradient.
gradient and normalizes aortic pressure waveform contours in HCM [22]. Wigle et al. showed that pharmacologic abolition of LVOT obstruction with angiotensin or surgical myectomy caused amelioration of MR while intensification of obstruction with isoproterenol or amyl nitrite increased MR [29]. However, in patients with primary mitral valve abnormalities coexisting with HCM, pharmacologic interventions may abolish the LVOT gradient without eliminating all MR, necessitating primary mitral valve repair or replacement surgery at the time of septal myectomy [31–34].
Discussion Hemodynamic catheterization is also required in complex scenarios such as the last patient where the modified Bernoulli equation [8] is not reliable in determining the relative hemodynamic contribution of obstruction in series [12–14]. This exists in HCM patients with aortic stenosis or other causes of subvalvular and supravalvular fixed stenosis. The contribution of obstruction at the level of the aortic valve can be derived by withdrawing a retrogradely placed catheter from just under the aortic valve into the aorta with another catheter in the LV inflow tract [12]. Alternatively, a progressive increase in afterload can be induced pharmacologically as described in case 3 using phenylephrine or other afterload increasing agents. Case 5: Pitfalls in Catheter Placement for Determining Level of Obstruction
Case 4: Serial Obstruction A 75-year-old woman presented for preoperative evaluation before orthopedic surgery. She had a history of HCM and had limited activity due to left hip osteonecrosis and femoral head collapse. On examination she was wheel-chair bound with a grade 3/6 ejection systolic murmur heard in the right upper sternal border with no change with the Valsalva maneuver. TTE showed serial stenosis in the LVOT and at the aortic valve with instantaneous maximal systolic gradients of up to 104 mm Hg. It was not possible to accurately determine the relative contribution of the different levels of obstruction and thus she was referred to the cardiac catheterization laboratory. It was felt important to document how much of the gradient was due to fixed
A 50-year-old man with a history of HCM presented with shortness of breath climbing a single flight of stairs, and described exertional and postprandial lightheadedness. On examination he had a sustained point of maximum impulse, an audible fourth heart sound, but no murmur. TTE suggested a thickened septum consistent with HCM but also noted an apical pouch. There was neither SAM of the mitral leaflets nor a resting LVOT gradient. He was referred to catheterization for further hemodynamic assessment given the severity of his symptoms. On retrograde cannulation, there was a 100 mm Hg gradient between the LV and the aorta. However, when the catheter was advanced to the apex via a transseptal route, there was no gradient between the LV inflow tract and the ascending aorta
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Fig. 7. Mid-cavitary obliteration. A. Late peaking Doppler signal was noted on surface transthoracic echocardiogram. B. Simultaneous pressure tracings from ascending aorta (Asc Ao) and left ventricular (LV) inflow tract demonstrating no left ventricular outflow tract (LVOT) obstruction. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
(Fig. 6). The gradient was revealed to exist only between the apical pouch and both the LV inflow tract and ascending aorta, without evidence of LVOT obstruction (Fig. 6, Supporting Information Movie 3). He underwent apical and mid ventricular debulking myectomy to enlarge the LV cavity. He reported no restriction with physical activity on follow up. Discussion
This case illustrates the importance of catheter placement for accurate assessment of the location of obstruction. We recommend recording the LV pressure from the LV inflow, immediately below the mitral valve using the transseptal technique described by Wigle et al. [16,17] whenever there is a clinically important question regarding the exact location of an increased gradient. The LV inflow pressure is invariably increased compared to the ascending aorta in cases of LVOT obstruction. The transseptal approach results in a direct line to the ventricular apex, and thus the catheter can then be advanced to the mid-ventricle and then to the apex. Placing an endhole catheter in a retrograde fashion in the LVOT proximal to the point of leaflet-septal contact can lead to an underestimate of an LVOT gradient via placement that is too proximal. In addition, with a retrograde approach the catheter is directed to lateral wall of the mid-ventricle and
may not be able to be positioned in the true apex of the LV. Case 6: Mid-Cavity Obliteration
A 79-year-old woman with a history of severe symptomatic hypertrophic cardiomyopathy presented 4 years after septal myectomy with 1 year of dyspnea on exertion. On physical examination, she had normal venous pressure and no audible murmur at rest, with Valsalva or squat-to-stand maneuvers. TTE showed a small hyperdynamic LV with concentric hypertrophy and no SAM; there was, however, a variable late peaking systolic Doppler signal measuring 2.3 m sec1 that raised concern of LVOT obstruction. She proceeded to undergo hemodynamic catheterization with simultaneous TTE demonstrating the same late peaking signal with no associated gradient between the LV inflow tract and ascending aorta (Fig. 7A and B). This confirmed an absence of LVOT obstruction, and led to a diagnosis of intermittent mid-cavitary obliteration. Discussion
Late-peaking systolic signals can be generated by complete cavity obliteration from a hypercontractile left ventricle in the absence of true obstruction as illustrated by our final case. The absence of a dynamic
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Hemodynamic Catheterization in Hypertrophic Cardiomyopathy
murmur and of lack of SAM of the mitral leaflets would suggest the absence of true LVOT obstruction [35,36]; however, in the setting of severe symptoms, invasive hemodynamic catheterization can be confirmatory [15].
CONCLUSION
TTE with continuous wave Doppler is the principal method to determine the presence and magnitude of LVOT obstruction in HCM. However, in severely symptomatic HCM patients where a significant LVOT gradient cannot be documented on TTE, invasive hemodynamic catheterization with pharmacologic provocation is useful in guiding therapy. In addition, in patients with serial stenosis, invasive hemodynamic catheterization is necessary to determine the relative hemodynamic contribution at different levels of obstruction. REFERENCES 1. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA study. Coronary artery risk development in (young) adults. Circulation 1995;92:785–789. 2. Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, Nistri S, Cecchi F, Udelson JE, Maron BJ. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 2006;114:2232– 2239. 3. Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 1995;92:1680–1692. 4. Wigle ED, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 1985;28:1–83. 5. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003;348:295–303. 6. Nishimura RA, Holmes DR. Clinical practice. Hypertrophic obstructive cardiomyopathy. N Engl J Med 2004;350:1320– 1327. 7. Writing Committee Members, Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: Executive summary: A report of the American college of cardiology foundation/American heart association task force on practice guidelines. Circulation 2011;124:2761–2796. 8. Hatle L. Noninvasive assessment of valve lesions with Doppler ultrasound. Herz 1984;9:213–221. 9. Nishimura RA, Tajik AJ. The valsalva maneuver-3 centuries later. Mayo Clin Proc 2004;79:577–578. 10. Nishimura RA, Ommen SR. Hypertrophic cardiomyopathy: The search for obstruction. Circulation 2006;114:2200–2202.
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34. Wan CKN, Dearani JA, Sundt TM, Ommen SR, Schaff HV. What is the best surgical treatment for obstructive hypertrophic cardiomyopathy and degenerative mitral regurgitation? Ann Thorac Surg 2009;88:727731; discussion 731–732. 35. Pollick C, Rakowski H, Wigle ED. Muscular subaortic stenosis: The quantitative relationship between systolic anterior motion and the pressure gradient. Circulation 1984;69:43–49. 36. Pollick C, Morgan CD, Gilbert BW, Rakowski H, Wigle ED. Muscular subaortic stenosis: The temporal relationship between systolic anterior motion of the anterior mitral leaflet and the pressure gradient. Circulation 1982;66:1087–1094.
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Hemodynamic Rounds The Role of Hemodynamic Catheterization in the Evaluation of Hypertrophic Obstructive Cardiomyopathy: A Case Series Kalkidan Bishu,1* MD, MS, Megan Coylewright,2 MD, MPH, and Rick Nishimura,3 MD Confirmation of the presence and magnitude of left ventricular outflow tract (LVOT) obstruction is a critical component of the evaluation of symptoms in patients with hypertrophic cardiomyopathy (HCM). The presence of LVOT obstruction in patients with severe symptoms refractory to pharmacologic therapy identifies a subgroup of HCM patients who may benefit from septal reduction therapy. Two-dimensional echocardiography with continuous wave Doppler is the main tool for confirming the presence and severity of LVOT obstruction in HCM. However, when uncertainty remains following non-invasive evaluation, invasive hemodynamics studies are required to confirm and quantify LVOT obstruction. In this manuscript we describe a series of 6 cases in which hemodynamic catheterization is instrumental in supplementing non-invasive imaging in the assessment of LVOT obstruction in HCM. VC 2015 Wiley Periodicals, Inc. Key words: cardiomyopathy; hypertrophic; catheterization; diagnostic; catheterization; transeptal; hemodynamics
INTRODUCTION
Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease characterized by thickening of the left ventricular wall in the absence of other cardiac or systemic diseases, affecting up to 0.2% of the general population [1]. Two-thirds of patients with HCM have a dynamic left ventricular outflow tract (LVOT) obstruction due to a mechanical impediment to blood flow caused by systolic anterior motion (SAM) of the mitral valve [2]. Confirmation of the presence, magnitude and location of obstruction in HCM is critical in the evaluation of patients with HCM because obstruction mediates the development of severe heart failure symptoms [3,4], impacts long term outcomes [5], and is the primary target for therapy [6]. Transthoracic echocardiography (TTE) with continuous wave Doppler is the principal diagnostic modality for determining the presence and magnitude of LVOT obstruction in HCM [7]. Direct visualization of SAM of the mitral valve contacting an area of septal hypertrophy in combination with a late peaking systolic velocity obtained by continuous wave Doppler across the outflow tract is necessary for the diagnosis of C 2015 Wiley Periodicals, Inc. V
subvalvular obstruction. The severity of obstruction can be obtained by applying the modified Bernoulli equation to the peak systolic Doppler outflow velocity [8]. Severe resting obstruction is present if the LVOT Additional Supporting Information may be found in the online version of this article. 1
Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado 2 Section of Cardiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 3 Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota Conflict of interest: Nothing to report. *Correspondence to: Kalkidan Bishu, M.D., M.S., Fellow in Interventional Cardiology, Department of Medicine, University of Colorado School of Medicine 12401 E. 17th Ave., #524, Aurora, CO 80045. E-mail: [email protected] Received 26 July 2014; Revision accepted 18 January 2015 DOI: 10.1002/ccd.25856 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com)
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Fig. 1. Catheter entrapment when LV outflow tract gradient is assessed using a retrograde approach. A. Pressure tracings from the LV inflow tract (LV) measured via a transseptal approach and the ascending aorta (Asc Ao) with no significant gradient B. Pressure tracings from the LV measured via a retrograde approach and the ascending aorta (Asc Ao) inaccurately demonstrating a gradient of 120 mm Hg in the absence of a spike and dome configuration of the aortic waveform confirming catheter entrapment.
gradient is >50 mm Hg. If no obstruction is detected at rest, provocative tests such as the Valsalva maneuver, exercise, or the use of inhaled amyl nitrite may bring out a latent obstruction [2,6,9]. One-third of patients with HCM have resting LVOT obstruction and an additional one-third may have LVOT obstruction with provocation [2]. Septal reduction therapy is indicated only for severely symptomatic patients who are intractable to optimal medical therapy and who are demonstrated to have severe obstruction [7]. Although determining the presence and magnitude of LVOT obstruction by noninvasive TTE is possible in the majority of patients, invasive hemodynamic catheterization may be required in a subset due to several reasons. First, in patients with no resting gradient, provocative maneuvers are required to elicit a latent obstruction, which may be difficult to capture with Doppler echocardiography, including during exercise [10]. The dynamic nature of obstruction in HCM can further confound the difficulty of capturing a transient gradient using Doppler echocardiography [11]. Second, contamination of the LVOT velocity Doppler signals may arise from a higher velocity mitral regurgitation (MR) signal, thus limiting accurate assessment of the gradient. Third, dynamic LVOT obstruction may
coexist with a fixed valvular aortic stenosis or subvalvular stenosis. Delineation of the contribution from dynamic LVOT obstruction is difficult given that assumptions for the modified Bernoulli equation traditionally used to estimate pressure gradients are invalid with obstruction in series [8,12–14]. Finally, latepeaking systolic signals upon Doppler interrogation can be generated by complete cavity obliteration from a hypercontractile LV, simulating LVOT obstruction [15]. The location of obstruction (outflow versus midventricle) may be difficult to determine by continuous wave Doppler echocardiography, which samples all velocities across the Doppler beam. In this case series, we illustrate the utility of hemodynamic catheterization as a complementary tool to echocardiography in helping establish the presence, magnitude and location of obstruction in patients with HCM. We wish to emphasize that the hemodynamic evaluation of patients with HCM takes a systematic approach as well as meticulous attention to detail. For identification of LVOT obstruction, we used a transseptal approach to measure the LV pressure from the LV inflow as described by Wigle et al. [16,17]. with simultaneous central aortic pressures. This avoids the potential problem of catheter entrapment, which can occur in the small hypertrophied ventricles and hyperdynamic contractility resulting in cavity obliteration, when using catheters from a retrograde aortic approach (Fig. 1). The placement of the catheter from a retrograde approach is usually in the lateral aspect of the mid-ventricle where catheter entrapment can occur. The transseptal approach may not be necessary in many patients in whom a retrograde approach would be adequate but is a reliable method to avoid entrapment when there is an important clinical question to be answered regarding the presence, severity, and location of the gradient. If a retrograde approach is taken, either an end-hole catheter or a catheter with an end hole and limited distal side holes should be used. In some institutions a properly calibrated and equalized pressure wire is used for measurement of LV pressure. Transseptal catheterizations should only be performed by operators who are highly experienced in this technique. CASE SERIES Case 1: Absence of Severe Resting Gradient
A 70-year-old woman presented with exertional shortness of breath for the past 2 years, already treated with low dose beta blocker for presumed HCM. On physical examination she had a soft grade 2/6 systolic ejection murmur at the left sternal border with a minimal increase with the squat-to-stand maneuver. TTE showed asymmetric hypertrophy of the basal
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Fig. 2. Use of isoproterenol to demonstrate latent left ventricular outflow tract (LVOT) obstruction. A. Pressure tracings from the ascending aorta (Asc Ao), LV inflow tract and left atrium (LA) demonstrating no LVOT gradient at rest. B. Pressure tracings from the Asc Ao, LV inflow tract and LA after intravenous administration of isoproterenol at 2 mcg min21 showing the development of a 90 mm Hg gradient in the LVOT.
interventricular septum with a resting LVOT gradient of 27 mm Hg. Doppler interrogation of the LVOT with Valsalva did not produce a clear signal to help identify a latent obstruction. It was unclear as to whether the etiology of her symptoms was due to more dynamic outflow obstruction, diastolic dysfunction or a noncardiac etiology. Thus further evaluation was pursued with a hemodynamic catheterization. On catheterization, there was no LVOT gradient at rest (Fig. 2A). However, following the administration of intravenous isoproterenol at 2 mcg min1 (Fig. 2B), a 90 mm Hg LVOT gradient was demonstrated. Her medical therapy was optimized with uptitration of beta blockers and her symptoms improved. The mean left atrial pressure was normal at less than 12 mmHg at rest and during provocation, ruling out diastolic dysfunction as an etiology of her symptoms. Discussion When there is no resting gradient, interventions such as the Valsalva maneuver, inhaled amyl nitrite or exercise may provoke a gradient that can be documented by TTE. Valsalva and amyl nitrite inhalation work similarly by reducing preload, which leads to an increase in the LVOT gradient [18]. Exercise testing, in which the gradient is measured during or immediately after bicycle or treadmill exercise, can also be
combined with Doppler echocardiography to determine the presence of a physiologically provocable LVOT gradient [7]. Elevated gradients are seen in response to increases in contractility and reduction in afterload. However, rapid respiratory movements during exercise may potentially interfere with Doppler interrogation of the LVOT [10]. Dobutamine infusion is not a recommended method to look for a provocable gradient [7]. Dobutamine increases myocardial contractility and heart rate via b1 receptors in the heart, but also increases total peripheral resistance and thus afterload via activation of a1 receptors [19]; this combination of effects counter one another in HCM. In addition, dobutamine may lead to cavity obliteration in patients with small, hypertrophied ventricles and cause an increased velocity not related to LVOT obstruction. Isoproterenol decreases total peripheral vascular resistance through its binding of b2 skeletal muscle smooth muscle receptors, decreases preload by binding venous b receptors and increases myocardial contractility and heart rate via b1 receptors leading to increased dynamic LVOT obstruction and a measurable gradient [19–21]. In an elegant early study, Braunwald et al. demonstrated a decrease in cardiac output, fall in systemic arterial pressure and an increase in left ventricular systolic pressure with intravenous administration of isoproterenol [22]. These hemodynamic changes were
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Fig. 3. LVOT Doppler contamination by a mitral regurgitation jet. A. Doppler echocardiographic interrogation of the left ventricular outflow tract (LVOT) after amyl nitrite inhalation shows a high-velocity, late-peaking signal with a contour that is atypical for LVOT obstruction and concerning for contamination from mitral regurgitation. B. Pressure tracings from ascending aorta (Asc Ao) and LV inflow tract demonstrating a 50 mm Hg gradient across the LVOT. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
also noted in patients with no LVOT gradient at baseline, illustrating the potential role of isoproterenol in subjects with latent obstruction [22–24]. Isoproterenol is typically used in the catheterization laboratory where invasive monitoring and rapid resuscitation is available. Intravenous infusion of isoproterenol or other inotropes such as norepinephrine may produce a gradient between the LV and aorta in dogs with LVH, normal human patients, or human patients with LVH without true LVOT obstruction [24–26]. The mechanism is multifactorial but may be (1) related to catheter entrapment or (2) early rapid and complete early ejection with cavity obliteration during late systole [27,28]. Outflow gradients can also be induced in normal ventricles during isoproterenol infusion due to an increase
in the inertial dynamics of LV ejection [26]. Transseptal catheterization will avoid entrapment in this scenario and integration of all clinical data including TTE evaluation for SAM of mitral leaflets that is easily performed during pharmacologic intervention in the catheterization lab will help distinguish other causes of a gradient from true LVOT obstruction. Thus, in selected patients in whom there is a high degree of suspicion that LVOT obstruction is responsible for drug refractory symptoms, pharmacologic provocation during hemodynamic catheterization may establish the presence of an inducible gradient. The simultaneous measurement of LV filling pressures may also be helpful to rule out diastolic dysfunction as an etiology of symptoms.
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Fig. 4. Secondary mitral regurgitation due to dynamic LVOT obstruction. A. Pressure tracings from ascending aorta (Asc Ao), LV inflow tract and left atrium (LA) at rest showing severe left ventricular outflow tract (LVOT) obstruction characterized by a spike and dome pattern in the Asc Ao and a 100 mm Hg gradient across the LVOT. LA pressure tracings showed a
large V wave consistent with severe mitral regurgitation shown in Supporting Information Movie 1. B. Pressure tracings from Asc Ao and LV inflow tract and LA after the administration of phenylephrine at 2 mcg kg21 min21 showing that the LVOT gradient and large V wave in the LA are gone, and the Asc Ao pressure contour has normalized.
Case 2: Contamination of LVOT Doppler Signal by MR Jet
regurgitation velocity was 5 m sec1 indicating the gradient between the left atrium and the LV was 100 mm Hg (estimated from the modified Bernoulli formula, gradient ¼ 4 V2, where V is the peak systolic velocity of Doppler flow signal). Of note, with an elevated LV systolic pressure of 160 mm Hg, the patient also had markedly elevated left atrial filling pressures. The patient underwent alcohol septal ablation and reported improvement in exertional symptoms on follow-up.
A 77-year-old man presented with symptoms of exertional chest pain and shortness of breath after walking less than 20 feet or when climbing a single flight of stairs. He was on maximally tolerated beta blocker and calcium channel blocker therapy. Physical examination revealed a soft systolic murmur that increased with the squat-to-stand maneuver. Coronary angiography showed no obstructive lesions. His TTE showed LV hypertrophy with prominent basal septum involvement. There was SAM of the mitral valve leaflet with mild, posteriorly directed regurgitation at rest, as well as with Valsalva and amyl nitrite administration. However, it was difficult to obtain the true LVOT signal on Doppler interrogation due to contamination of the signal by the MR jet. Given a lack of clarity regarding a benefit from septal reduction therapy, the patient proceeded to hemodynamic catheterization. This demonstrated a 50 mm Hg gradient between the LVOT and the ascending aorta, while the Doppler signal of nearly 5 m sec1 suggested a gradient of 100 mm Hg (modified Bernoulli equation ¼ 4 V2) [8]. Thus, the Doppler signal was shown to be representative of the mitral regurgitant jet during systole, approximating the gradient between LV systolic pressure and LA (Fig. 3A and B). Peak mitral
Discussion
LVOT obstruction is identified as a high-velocity, late-peaking concave signal on continuous wave Doppler associated with SAM of the mitral valve leaflet on 2D echocardiography. The modified Bernoulli equation is applied to the peak instantaneous velocity across the LVOT to calculate the maximum gradient [8]. However, as shown in this patient, high-velocity MR jets may contaminate the late-peaking signal or be misidentified as an LVOT signal [15]. This scenario requires invasive hemodynamic catheterization. We were able to accurately measure the gradient between the LV inflow tract and ascending aorta using a catheter placed in the LV inflow tract via a transseptal puncture and a second side-hole catheter placed in the aortic root in a retrograde fashion [16,17].
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Fig. 5. Serial stenoses. A. Pressure tracings from ascending aorta (Asc Ao) and left ventricular (LV) inflow tract demonstrating a 120 mm Hg gradient in the left ventricular outflow tract (LVOT). B. When the catheter in the LV inflow tract is advanced to the LVOT just under the aortic valve leaflets, a smaller pressure gradient across the aortic valve of 20 mm Hg remains. C. A 100 mm Hg gradient between the LV inflow
tract and catheter placed in LVOT just under the aortic valve. D. Following administration of phenylephrine at 1 mcg kg21 min21, there is higher pressure in the Asc Ao. The gradient between the LV inflow and the Asc Ao decreased to 30 mm Hg indicating a significant dynamic LVOT obstruction with only moderate aortic valve stenosis.
Case 3: Increasing Afterload to Distinguish Dynamic, Secondary MR From Primary MR A 69-year-old woman presented with a history of persistent dyspnea climbing stairs for the past 5 years. Despite talc pleurodesis for a transudative left pleural effusion and an atrial fibrillation ablation, she had no improvement in symptoms. On physical examination, she had a harsh grade 2/6 mid-peaking systolic ejection murmur at the left sternal border that ended before the second heart sound. This murmur increased with the squat-to-stand and Valsalva maneuvers. She had a separate, grade 2/6 holosystolic murmur at the cardiac apex. TTE showed LV hypertrophy with asymmetric septal involvement and a heavily calcified mitral annulus with significant MR which was inadequately graded. The patient was referred for evaluation for septal reduction therapy. However, it was not clear if she needed septal myectomy with mitral valve surgery or solely septal reduction therapy (via either septal myectomy or alcohol septal ablation). During cardiac catheterization, there was a resting LVOT gradient of 100 mm Hg (Fig. 4A) and severe MR (Supporting Information Movie 1). Following the administration of phenylephrine at 2 mcg kg1 min1, the LVOT gradient was abolished (Fig. 4B) and MR was only mild (Supporting Information Movie 2) indicating the MR was secondary to SAM and associated with dynamic LVOT obstruction. The patient underwent
septal myectomy and was able to exercise daily without limitations.
Discussion Mitral regurgitation in HCM is predominantly functional and related to SAM. The dynamic nature of MR in HCM can be demonstrated by changes in the severity of the MR on physical examination as its severity increases with maneuvers that worsen LVOT obstruction (Valsalva and squat-to-stand maneuvers). Pharmacologic interventions that increase afterload reduce dynamic MR due to SAM and in turn, lower the LVOT gradient, while interventions that worsen MR by reducing afterload (inotropic agents or vasodilators) increase the degree of obstruction [29,30]. A progressive increase in afterload can be induced pharmacologically by using peripheral a1 receptor agonists such as methoxamine or phenylephrine to suppress dynamic LVOT obstruction [20,22]. Both methoxamine and phenylephrine are direct-acting a1 receptor agonists that increase total peripheral resistance by causing vasoconstriction in cutaneous, splanchnic, renal and skeletal circulation, and decrease heart rate in a vagally mediated reflex [19] leading to a reduction in SAM of the mitral leaflets and a demonstrably lower LVOT obstruction [29,30]. Braunwald et al. demonstrated that intravenous methoxamine abolishes the resting LVOT
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obstruction of aortic valve stenosis versus dynamic left ventricular outflow obstruction. If the former, surgical intervention with aortic valve replacement would be pursued prior to noncardiac surgery. On hemodynamic catheterization, a gradient between the LV inflow tract and ascending aorta of 120 mmHg was measured (Fig. 5A). A gradient of 20 mm Hg was measured between the ascending aorta and a catheter placed immediately below the aortic valve in the LV outflow tract (Fig. 5B) indicating the LVOT gradient was 100 mm Hg (seen in Fig. 5C). Following the administration of phenylephrine at 1 mcg kg1 min1, the gradient between the LV inflow tract and ascending aorta decreased to 30 mmHg (Fig. 5D). These findings were consistent with a prominent contribution of dynamic subvalvular LVOT obstruction rather than severe aortic stenosis. She was placed on maximal beta blocker therapy and underwent successful left hip replacement surgery.
Fig. 6. Obstruction at apical pouch. A gradient exists between the apical pouch and LV inflow tract, but not between the LV inflow and ascending aorta (Asc Ao) indicating a lack of LVOT gradient.
gradient and normalizes aortic pressure waveform contours in HCM [22]. Wigle et al. showed that pharmacologic abolition of LVOT obstruction with angiotensin or surgical myectomy caused amelioration of MR while intensification of obstruction with isoproterenol or amyl nitrite increased MR [29]. However, in patients with primary mitral valve abnormalities coexisting with HCM, pharmacologic interventions may abolish the LVOT gradient without eliminating all MR, necessitating primary mitral valve repair or replacement surgery at the time of septal myectomy [31–34].
Discussion Hemodynamic catheterization is also required in complex scenarios such as the last patient where the modified Bernoulli equation [8] is not reliable in determining the relative hemodynamic contribution of obstruction in series [12–14]. This exists in HCM patients with aortic stenosis or other causes of subvalvular and supravalvular fixed stenosis. The contribution of obstruction at the level of the aortic valve can be derived by withdrawing a retrogradely placed catheter from just under the aortic valve into the aorta with another catheter in the LV inflow tract [12]. Alternatively, a progressive increase in afterload can be induced pharmacologically as described in case 3 using phenylephrine or other afterload increasing agents. Case 5: Pitfalls in Catheter Placement for Determining Level of Obstruction
Case 4: Serial Obstruction A 75-year-old woman presented for preoperative evaluation before orthopedic surgery. She had a history of HCM and had limited activity due to left hip osteonecrosis and femoral head collapse. On examination she was wheel-chair bound with a grade 3/6 ejection systolic murmur heard in the right upper sternal border with no change with the Valsalva maneuver. TTE showed serial stenosis in the LVOT and at the aortic valve with instantaneous maximal systolic gradients of up to 104 mm Hg. It was not possible to accurately determine the relative contribution of the different levels of obstruction and thus she was referred to the cardiac catheterization laboratory. It was felt important to document how much of the gradient was due to fixed
A 50-year-old man with a history of HCM presented with shortness of breath climbing a single flight of stairs, and described exertional and postprandial lightheadedness. On examination he had a sustained point of maximum impulse, an audible fourth heart sound, but no murmur. TTE suggested a thickened septum consistent with HCM but also noted an apical pouch. There was neither SAM of the mitral leaflets nor a resting LVOT gradient. He was referred to catheterization for further hemodynamic assessment given the severity of his symptoms. On retrograde cannulation, there was a 100 mm Hg gradient between the LV and the aorta. However, when the catheter was advanced to the apex via a transseptal route, there was no gradient between the LV inflow tract and the ascending aorta
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Fig. 7. Mid-cavitary obliteration. A. Late peaking Doppler signal was noted on surface transthoracic echocardiogram. B. Simultaneous pressure tracings from ascending aorta (Asc Ao) and left ventricular (LV) inflow tract demonstrating no left ventricular outflow tract (LVOT) obstruction. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
(Fig. 6). The gradient was revealed to exist only between the apical pouch and both the LV inflow tract and ascending aorta, without evidence of LVOT obstruction (Fig. 6, Supporting Information Movie 3). He underwent apical and mid ventricular debulking myectomy to enlarge the LV cavity. He reported no restriction with physical activity on follow up. Discussion
This case illustrates the importance of catheter placement for accurate assessment of the location of obstruction. We recommend recording the LV pressure from the LV inflow, immediately below the mitral valve using the transseptal technique described by Wigle et al. [16,17] whenever there is a clinically important question regarding the exact location of an increased gradient. The LV inflow pressure is invariably increased compared to the ascending aorta in cases of LVOT obstruction. The transseptal approach results in a direct line to the ventricular apex, and thus the catheter can then be advanced to the mid-ventricle and then to the apex. Placing an endhole catheter in a retrograde fashion in the LVOT proximal to the point of leaflet-septal contact can lead to an underestimate of an LVOT gradient via placement that is too proximal. In addition, with a retrograde approach the catheter is directed to lateral wall of the mid-ventricle and
may not be able to be positioned in the true apex of the LV. Case 6: Mid-Cavity Obliteration
A 79-year-old woman with a history of severe symptomatic hypertrophic cardiomyopathy presented 4 years after septal myectomy with 1 year of dyspnea on exertion. On physical examination, she had normal venous pressure and no audible murmur at rest, with Valsalva or squat-to-stand maneuvers. TTE showed a small hyperdynamic LV with concentric hypertrophy and no SAM; there was, however, a variable late peaking systolic Doppler signal measuring 2.3 m sec1 that raised concern of LVOT obstruction. She proceeded to undergo hemodynamic catheterization with simultaneous TTE demonstrating the same late peaking signal with no associated gradient between the LV inflow tract and ascending aorta (Fig. 7A and B). This confirmed an absence of LVOT obstruction, and led to a diagnosis of intermittent mid-cavitary obliteration. Discussion
Late-peaking systolic signals can be generated by complete cavity obliteration from a hypercontractile left ventricle in the absence of true obstruction as illustrated by our final case. The absence of a dynamic
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murmur and of lack of SAM of the mitral leaflets would suggest the absence of true LVOT obstruction [35,36]; however, in the setting of severe symptoms, invasive hemodynamic catheterization can be confirmatory [15].
CONCLUSION
TTE with continuous wave Doppler is the principal method to determine the presence and magnitude of LVOT obstruction in HCM. However, in severely symptomatic HCM patients where a significant LVOT gradient cannot be documented on TTE, invasive hemodynamic catheterization with pharmacologic provocation is useful in guiding therapy. In addition, in patients with serial stenosis, invasive hemodynamic catheterization is necessary to determine the relative hemodynamic contribution at different levels of obstruction. REFERENCES 1. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA study. Coronary artery risk development in (young) adults. Circulation 1995;92:785–789. 2. Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, Nistri S, Cecchi F, Udelson JE, Maron BJ. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 2006;114:2232– 2239. 3. Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 1995;92:1680–1692. 4. Wigle ED, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 1985;28:1–83. 5. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003;348:295–303. 6. Nishimura RA, Holmes DR. Clinical practice. Hypertrophic obstructive cardiomyopathy. N Engl J Med 2004;350:1320– 1327. 7. Writing Committee Members, Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: Executive summary: A report of the American college of cardiology foundation/American heart association task force on practice guidelines. Circulation 2011;124:2761–2796. 8. Hatle L. Noninvasive assessment of valve lesions with Doppler ultrasound. Herz 1984;9:213–221. 9. Nishimura RA, Tajik AJ. The valsalva maneuver-3 centuries later. Mayo Clin Proc 2004;79:577–578. 10. Nishimura RA, Ommen SR. Hypertrophic cardiomyopathy: The search for obstruction. Circulation 2006;114:2200–2202.
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