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Logo of thijTexas Heart Institute JournalSee also Cardiovascular Diseases Journal in PMCSubscribeSubmissionsTHI Journal Website
 
Tex Heart Inst J. 2007; 34(3): 336–346.
PMCID: PMC1995043

The “1st Septal Unit” in Hypertrophic Obstructive Cardiomyopathy

A Newly Recognized Anatomo-Functional Entity, Identified during Recent Alcohol Septal Ablation Experience

Abstract

In hypertrophic obstructive cardiomyopathy, selective and asymmetric hypertrophy results in a stenotic subaortic channel, which is further narrowed by a Venturi effect (suctioning of the anterior leaflet, manifested by systolic anterior motion of the mitral valve). Better understanding of these essential pathophysiologic mechanisms has led to the definition of a new anatomo-functional entity, the 1st septal unit, which consists of the basal interventricular septal hypertrophy and its related septal arterial branches. As an alternative to surgical myomectomy, alcohol septal ablation is an effective method of reducing subaortic stenosis and improving mitral valve function. After alcohol ablation, global negative remodeling of the hypertrophied left ventricle eventually ensues.

This review presents specific anatomic and functional features of a newly identified pathophysiologic entity (the 1st septal unit) in relation to the clinical manifestations and natural history of hypertrophic obstructive cardiomyopathy. This relationship is also relevant during the performance of alcohol septal ablation interventions: related operative suggestions are provided for optimizing subaortic stenosis relief during septal ablation and for preventing complications.

Key words: Alcohol septal ablation, asymmetric septal hypertrophy, cardiomyopathy, hypertrophic obstructive/physiopathology/therapy, coronary vessels/anatomy, ethanol/therapeutic use, first septal unit, heart septum

Since 1994, when Ulrich Sigwart1 introduced alcohol septal ablation (ASA) into clinical practice, this method has become an important option for treating symptomatic hypertrophic obstructive cardiomyopathy (HOCM).2–14 Alcohol injection into a septal branch had previously been used by Brugada and coworkers15 for ablating ventricular tachycardia. In accordance with the natural history of HOCM,16,17 the main indications for ASA are substantial functional impairment, as characterized by New York Heart Association functional class III or IV status (dyspnea, angina, or syncopal equivalents), and a subaortic gradient of more than 50 mmHg.2–14 In selected patients with these criteria, ASA results in a level of clinical improvement similar to that seen after a surgical septal myomectomy18–27; moreover, ASA effectively relieves subaortic stenosis and mitral insufficiency.

The medical literature commonly states that the largest proximal, upper (also called “the 1st”) septal branch should be the target of ASA,1–14 that 5% to 40% of candidates present technical difficulties (a “nonsuitable” 1st septal branch),1–14,28,29 and that 5% to 10% of patients require a 2nd ASA procedure to obtain adequate relief.1–14 On the basis of our recent experience with ASA, we present some observations that posit the existence of a newly recognized (as defined here) anatomo-functional entity that seems to determine the severity and prognosis of HOCM: the 1st septal unit (FSU), which consists of the 1st septal coronary branch and its dependent (asymmetric) septal hypertrophy, at the level of mitral-septal contact (Fig. 1). We also discuss procedural considerations that may further the understanding of HOCM and improve the results of ASA.

figure 13FF1
Fig. 1 Cardiac magnetic resonance image of a left ventricular longitudinal cross-section shows the treatment site 3 days after alcohol septal ablation. In this patient, at this stage, the anterior leaflet of the mitral valve still touches the ventricular ...

The Nature of Subaortic Stenosis in Hypertrophic Cardiomyopathy

It has long been debated whether asymmetric septal hypertrophy is a critical component or an irrelevant epiphenomenon of HOCM.30–38 In this complex condition, asymmetric septal hypertrophy has been observed on echocardiography to be accompanied by systolic anterior displacement of the mitral valve apparatus (systolic anterior motion or SAM), which constitutes the posterior portion of the obstructed left ventricular outflow tract.30–38 The high systolic flow velocity created at the subaortic level by SAM further worsens the stenosis, because the anterior leaflet of the mitral valve is suctioned into the outflow tract by a Venturi effect.38,39 For many years, the induction of negative remodeling of the upper (basal) septum was surgically pursued as a way to relieve subaortic obstruction. Diffuse left ventricular negative remodeling (reabsorption of hypertrophic myocardium) and even improvement of secondary mitral insufficiency were noted as consequences of the intervention.1–14,18–27,40 Using alcohol septal ablation, we aim at producing similar results by the subselective administration of pure or absolute alcohol into the FSU-related septal branch(es) via a catheter procedure. Pure alcohol causes immediate coagulative necrosis of the targeted territory, as discussed below. The results of both surgical septal myomectomy and ASA suggest that the FSU is indeed a critical factor that establishes both the severity and the prognosis of HOCM in individual patients16,17,36; moreover, substantial removal (negative remodeling) of the FSU, by any means, leads to dramatic limitations in the clinical repercussions and the progression of HOCM, which confirms the central role of the FSU (Fig. 2).

figure 13FF2
Fig. 2 Drawing shows the basic pathophysiologic mechanisms of hypertrophic obstructive cardiomyopathy (HOCM) and the feedback actions involved. An initial congenital genetic disorder causes primary hypertrophy, or hypertrophic cardiomyopathy (HCM), which ...

Arterial Supply to the 1st Septal Unit and Alcohol Septal Ablation

In human beings, the ventricular septum is normally sup-plied with blood by anterior and posterior septal pene-trating coronary branches. The left anterior descending artery (LAD) supplies approximately two thirds of the septum (the anterior portion), and the posterior descend-ing artery (which arises from the right coronary or circumflex artery, depending on the dominance pattern) provides branches that supply the posterior portion of the septum.41–45 Neighboring anterior and posterior septal branches are richly interconnected by a network of (usually small) collateral vessels, as shown in detailed classic anatomic studies41 (Fig. 3). After occlusion of the LAD or posterior descending branch, collateral vessels rapidly become dilated. Typically, only in this context are they angiographically visible in human beings.

figure 13FF3
Fig. 3 Radiograph of a human necropsy specimen injected with contrast medium shows the arterial vascularization of the ventricular septum. The ventricular free walls have been removed, and only the anterior (right-sided) and posterior descending (left-sided) ...

Selective obliteration of one or more septal branches by means of temporary balloon inflation, coils, or covered stents46–48 has occasionally been performed to induce septal ischemia, hibernation, or necrosis. These approaches produce much smaller infarctions and less negative remodeling than does ASA.46–48 For example, in 1 case reported by Fifer and coworkers,47 implantation of a covered stent led to initial resolution of a large subaortic gradient associated with a modestly elevated creatine kinase level (peak, 363 U/L). After 10 months, however, the gradient and the patient's symptoms recurred, when collateral circulation developed from the right coronary artery to the 1st septal branch. The authors hypothesized that the initial hibernation state was reversed with the onset of collateral blood flow.47

During ASA, the operator not only can observe the detailed anatomy of the septal branches but also can perform both subselective septal contrast angiography (with the same balloon catheter) and contrast echocardiography.14,40,49 Nevertheless, precision is suboptimal with both of these techniques, because they indicate only the core of the eventual alcohol accumulation (alcohol diffuses through the tissues much more extensively and rapidly than do high-viscosity contrast agents). In addition, the targeted septal branch becomes occluded by clot shortly after alcohol administration begins, which changes the pattern of fluid progression. In the presence of visible collateral vessels, especially in the case of critical obstruction or occlusion of the proximal right coronary artery, alcohol injected at high pressures or in large volumes into an anterior septal vessel inevitably spills over into the posterior circulation and causes remote damage, which has occasionally been reported in the literature.1–14,40

Until advanced experience was gained with ASA, the concept of the 1st septal branch in the FSU was poorly defined in clinical practice and in the literature. Over time, it has become evident that, in treating HOCM, the operator must identify the septal branch(es) that supply the basal third of the interventricular septum, at the site of mitral-septal contact (kissing) or SAM of the mitral valve. Indeed, frequently, the anatomic 1st penetrating branch of the LAD (which technically can be negotiated by a balloon catheter) is not related to the FSU or is not the only or most favorable vessel related to it.11,14,40 The anatomic 1st septal branch of the LAD can be a small one (<1 mm in diameter) that supplies only a trivial upper portion of the septum (and possibly the bundle of His or the proximal left bundle branch) (Fig. 4) but not the portion related to SAM in the FSU. In other instances, the 1st septal branch originates from the diagonal or circumflex arteries or even from the left main trunk, right anterior sinus, or right coronary artery (Fig. 5).45 Sometimes, the 1st septal branch is a large vessel that continues subepicardially, like a duplicate LAD, and provides most of the septal branches. Frequently, close to its origin, the 1st septal branch splits into 2 vessels: 1 that typically extends to the right side of the septum (and the moderator band) and another that supplies the left side of the upper septum at the level of SAM (Fig. 6). Incidentally, the moderator band (the only structure to connect the upper ventricular septum with the free wall of the right ventricle) usually carries the right bundle branch.50 The consistent origination of the moderator-band coronary branch from the 1st septal branch is a likely reason for the almost inevitable appearance of some degree of right bundle-branch block after successful ASA.51–53 Occasionally, right ventricular branches (not septal branches) originate from the mid portion of the LAD (Fig. 7), and they should be avoided during ASA.

figure 13FF7
Fig. 7 A) Preoperative left coronary angiogram in the right anterior oblique projection. Four branches (1–4) arising from the proximal left anterior descending coronary artery are potential candidates for alcohol infusion. On echocardiography, ...
figure 13FF4
Fig. 4 Echocardiographic images obtained by injecting the 1st (A) and 2nd (B) septal branches. Note that the injection of albumex at the 1st septal branch reveals the uppermost portion of the septum (arrow), above the level of systolic anterior motion ...
figure 13FF5
Fig. 5 Preoperative coronary angiograms from a patient with a complex coronary anomaly involving right-sided origination of all 3 major coronary vessels. A) The right coronary artery originates normally. B) An anterior artery (with a prepulmonary course) ...
figure 13FF6
Fig. 6 A) Right anterior oblique angiogram of the left coronary artery (LCA) shows 2 parallel septal branches (right-sided branch, R; left-sided branch, L). B) Left anterior oblique cranial angiogram of the LCA shows the sidedness of the 2 septal branches. ...

In a minority of cases (10% to 30%), successful ASA necessitates selective administration of alcohol into more than 1 septal branch, because the anatomic 1st septal branch is relatively small; to achieve adequate septal remodeling, a 2nd branch must be treated during the initial procedure or a later one.1–14

Like any other septal branch, the 1st septal has a rich anastomotic network41 that extends distally along the septum, toward the apex (as shown in Fig. 3). A relatively high pressure, speed, or volume of injection of alcohol during ASA can result in distal leakage into the neighboring septal branches and even into the epicardial LAD (as demonstrated by the occurrence of infarcts in areas remote from the target, in the lateral wall of the left ventricle).11,14,40

In cases of HOCM, the 1st septal branch frequently shows angiographic systolic blanching or a milking effect, which is also an angiographic expression of myocardial disarray and high (suprasystemic) intramural pressures. Because of proximal balloon inflation during ASA, the infused alcohol must be subjected to a high systolic pressure in the presence of distal vessel occlusion by blood clot. This situation may encourage the progression of the injected, low-density fluid toward anastomotic connections. At the same time, this peculiar hemodynamic regimen can promote the favorable effect of alcohol filtration through the neighboring tissues, if the injection is at a slow rate. Alternatively, if the balloon does not properly seal the instrumented septal branch, backward flow into the epicardial LAD can occur, posing an inherent risk of remote-site myocardial alcoholization. This potential is confirmed by Doppler flow-velocity studies, which have shown that retrograde systolic flow frequently occurs in epicardial vessels in cases of HOCM.54 Soon after alcoholization starts, however, local akinesia may mitigate intramural systolic suprasystemic hypertension.

In the literature and in practice, there has been much discussion concerning the ideal volume and flow rate of alcohol infusion.1–14,40 The initial use of a 2- to 5-cc infusion over a period of about 30 seconds1,3 has recently been challenged.11,14,40 The total quantity and the speed of alcohol injection appear to be fundamental determinants of adequate results.11,40 The operator tries to prevent atrioventricular (AV) block and overspills from the target territory—the 2 major complications of excessive alcoholization. The dependent, targeted territory of the functional 1st septal unit is actually predetermined by subselective angiography and contrast echocardiography. The infusion rate should be fairly slow (about 1 cc over 30 to 60 seconds) and continuous; intermittent, rapid bolus administration would likely increase the risk of overspilling, because the low-viscosity fluid could tend to progress into more distal collateral coronary branches and might not diffuse into the neighboring tissues as intended. Although some operators recommend that the alcohol infusion be followed by a saline bolus to flush the alcohol away from the catheter,40 this practice may promote unwanted alcoholi-zation of remote, critical tissues such as the AV node. The balloon is commonly kept inflated for at least 5 minutes after the end of the alcohol infusion,14,40 mainly to allow clot organization and prevent vascular runoff of alcohol, while encouraging the highly diffusible alcohol to seep through the tissues, preventing dilution.

Potentially, any variation in the coronary artery anatomy is treatable by means of ASA, although the technique must be tailored to the specific anatomy of each patient and may require special operative skills. In some cases, the balloon catheter should be advanced subselectively to include only part of a large septal branch; in other cases, the quantity of alcohol injected into 1 septal branch should be limited to prevent overspilling in 1 direction (a visible collateral), or more than 1 septal branch may need to be treated (creative sculpting is frequently required).

Avoiding the onset of complete AV block (while keeping a temporary pacemaker in place during and for 2–3 days after ASA) is of paramount importance, not only because it makes ASA easier and less expensive, but also because it reduces the risk of AV block after hospital discharge—a potential cause of death.55–57 In fact, after ASA, the onset of AV block can be quite insidious, and sometimes arises after the 48-hour period during which a temporary pacing catheter is routinely kept in place and the patient is closely monitored. In addition, after ASA, complete AV block tends to present suddenly, and frequently leads to a poor escape fascicular or ventricular rhythm (even ventricular asystole), likely because these alternative pacemakers also may be abolished by ASA.55–57 Delayed AV block (observed after 10%–25% of procedures11,14,40,51–53) is more likely due to edema or to hemorrhage-related impairment55–57 than to alcohol-related direct necrotic injury, and often disappears spontaneously within a month. To decrease the risk of AV block, we recently tested the hypothesis that contralateral infusion of lactated Ringer's solution (subselectively infused at the AV-node artery, a branch of the distal right coronary artery) simultaneously with normal anteroseptal administration of alcohol may protect the AV node (Fig. 8). Our initial results with this investigative technique have been favorable yet inconclusive.

figure 13FF8
Fig. 8 A) Angiogram in the right anterior oblique projection shows the 1st septal branch (asterisk), which is the target of alcohol septal ablation. B) Angiogram of the right coronary artery in the left anterior oblique view reveals the subselective location ...

Mechanism of Action of Alcohol Septal Ablation

The basic mechanism of ASA is usually assumed to be shrinkage (in fact, ablation) of the infarcted area of myocardium. This assumption, however, fails to acknowledge that the favorable effects of ASA progress over time,58,59 typically in 3 phases:

  1. Perioperative: The “Flaccid Akinesia” Phase. By the same definition as that of successful ASA, the subaortic gradient is either totally or substantially obliterated after induction of coagulation necrosis (in the absence of any real ablation or tissue removal).
  2. Early Postoperative: The “Edematous Halo” Phase. The subaortic gradient frequently recurs 1 to 3 days after ASA.58,59 It recedes in 5 to 10 days.
  3. Late Postoperative: The “Dense Scar” Phase. The subaortic gradient gradually decreases substantially and permanently. This stage is complete 3 to 12 months after ASA7,8,12,13,40 (Fig. 7).

During the initial, perioperative phase of flaccid aki-nesia, the behavior of subaortic stenosis is surprising and hard to explain in the absence of real ablation of the FSU. Akinesia, resulting from myonecrosis and secondary flaccidity of the treated upper portion of the septum, is the most likely reason for the immediate abolition of, or substantial decrease in, the outflow gradient at a stage in which there is no physical loss of tissue. During this early phase, left ventricular systolic pressure seems to cause temporary reshaping and widening of the outflow tract: the consequent diminution of the outflow blood velocity disrupts the Venturi effect, reducing the tendency of the anterior mitral valve leaflet to undergo SAM.39 Only by chance does early diminution of the subaortic gradient correspond so closely to that expected in the late phase, when true absorption of the scarred myocardium is complete (Fig. 9).

figure 13FF9
Fig. 9 Postoperative cardiac magnetic resonance images, all from the same patient, in the longitudinal (4-chamber) (A, B) and cross-sectional (C, D) views. Comparisons of the early images, obtained on day 2 (A, C) and the late images, obtained on day ...

In reality, the determination and interpretation of both the preoperative baseline gradient and the postoperative final result is the topic of an evolving discussion in HOCM treatment. To determine a “true” baseline gradient, it has become standard practice to 1) withhold negative inotropic medications that would decrease the obstruction (especially disopyramide and β-blockers) for at least 2 days before ASA and 2) avoid diuretics, vasodilators, and other agents that might increase the gradient. As hemodynamicists and echocardiographers know, the HOCM gradient varies widely during any given observation period, even with minor changes in levels of respiratory effort, hydration, sedation, or anxiety. To “normalize the gradient” and improve the reliability of this marker of HOCM severity, one could try to induce the worst possible scenario for a given patient, for example by the administration of nitroglycerin (which is inexpensive and immediately available in the catheterization laboratory), dobutamine, or isoproterenol, or by inducing a premature ventricular contraction by programmed pacing.11,14,40

The early postoperative (“edematous halo”) phase is not a universal feature: it occurs in 50% to 60% of patients undergoing ASA.58,59 When present, this phase involves recurrence of the gradient, the systolic murmur, the mitral regurgitation, and the SAM, as shown by echo-cardiography.59

The cause of this phenomenon is obscure. To observers who are unprepared for it, the recurrence of the gradient is disappointing and confusing; in the early practice of the procedure, several patients even underwent an early, secondary surgical myomectomy due to the apparent failure of ASA.

Our preliminary cardiac magnetic resonance imaging studies have suggested that the onset of a variable degree of edema, hemorrhage, or both, at the site of alcoholization causes the recurrence of aortic stenosis by inducing increased turgor of the damaged myocardium (Fig. 9). The few available pathologic studies of necropsy specimens obtained a few days after ASA indicate that the infarcted territory bulges at this stage and that retractive scarring ensues only during the late period.55,56 Of note, at this stage (in the presence of a recurrent gradi-ent), patients typically continue to report substantial resolution of most symptoms (especially of chest pain or pressure), likely because of the alcoholization of sensory nerve endings and infarction of the culprit territory (where pain is apparently generated), rather than actual resolution of the subaortic stenosis.

During the late postoperative (“dense scar”) phase, mature scarring is accompanied by substantial thinning of the treated area1–14 (Fig. 9) and by definitive reduction of the subaortic gradient. Usually, SAM and mitral insufficiency are also substantially reduced at this stage.11,14,40 According to initial serial observations, over the 1st few years either after surgical myomectomy or after ASA, diffuse hypertrophy of the free left ventricular wall does not progress, as would otherwise be expected; rather, the ventricular wall undergoes substantial negative remodeling, losing 10% to 30% of its mass.1–14,40,60–64

Current experience indicates that an initial infarction involving some 15 to 20 g of myocardium results in the final ablation of about 129 g of left ventricular mass.63 Interestingly, during a myomectomy, surgeons remove only 3 g of myocardium on average,65 yet eventually achieve an even greater regression of hypertrophy at 1 year (reportedly, some 150 g).63 Most likely, the myotomy (longitudinal incision) that surgeons perform simultaneously with the myectomy (removal of myocardium) is an important contributor to their final result.

All of these findings support the belief that subaortic stenosis is a major factor in the progressive nature of HOCM—a genetic condition that affects initially and primarily the individual myofibers. Moreover, ASA consistently leads to stabilization and even regression of hypertrophy in HOCM, just as a surgical myomectomy does in the same condition, or as aortic valve replacement does in severe cases of aortic valve stenosis.

Arrhythmias

In any given case of HOCM, the risk of ventricular arrhythmias or sudden death occurring is not quite clear, nor is the effect of ASA on these risks. The frequent appearance of right bundle-branch block and other conduction defects after ASA51–53 and the formation of new scar tissue might be assumed to increase the risk of arrhythmias.26,66 On the contrary, the fact that most ventricular arrhythmias in HOCM seem to originate from the subaortic septum (which, after ASA, becomes predominantly a dense, electrically silent scar15,55,56) suggests that the risk of arrhythmias might be reduced (similarly to when alcohol is used for electrical ablation15). At our institution and at others, some patients have been treated with prophylactic automatic implantable cardiac defibrillators after ASA, as recommended by Maron and colleagues,66 but follow-up observations have indicated that the rates of arrhythmias and shock are quite low.11,14,40 Larger ASA series with long-term follow-up studies are necessary to establish definitive conclusions and recommendations in this regard.

Conclusion

For the treatment of symptomatic HOCM, ASA is a simple, expeditious option that offers important benefits affecting multiple aspects of this complex pathologic state. Cardiologists who perform ASA should become familiar with the newly recognized anatomo-functional entity, the FSU. The extent of septal hypertrophy and the number, size, intrinsic anatomy, and collateral connections of the relevant septal branches vary in individual cases, which contributes to the complexity of ASA interventions. Nuclear magnetic resonance imaging is an ideal complement to echocardiography for establishing the mechanisms of ASA and evaluating the changes in HOCM after this procedure.

A crucial, often difficult issue that deserves further investigation is how to determine the extent of the FSU in a given case. Defining the exact FSU borders seems to elude interventional cardiologists as it does cardiovascular surgeons, who have long struggled to establish clear guidelines concerning the length of myectomies.18–26 Because variations in specific features of the FSU are the main reason for this uncertainty (unlike, for instance, the consistency in aortic valve stenosis and its treatment), a better understanding of the anatomic, functional, and technical concepts discussed above is essential for optimizing the results of ASA.

For any given case, the objectives of ASA should be as follows: 1) substantial reduction of the subaortic gradient (achieved through immediate necrosis of the treated area that leads to delayed anatomic ablation); 2) elimination of the Venturi effect at the subaortic level, which should abolish or decrease SAM and secondary mitral regurgitation; 3) progressive, delayed negative remodel-ing of ventricular hypertrophy (and possibly prevention of the evolution of HOCM into dilated cardiomyopathy38,39); and 4) avoidance of AV blockade, ventricular tachycardia, and sudden death.

Footnotes

Address for reprints: Paolo Angelini, MD, P.O. Box 20206, Houston, TX 77225–0206. E-mail: moc.rr.notsuoh@dminilegnap

References

1. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995;346:211–4. [PubMed]
2. Shamim W, Yousufuddin M, Wang D, Henein M, Seggewiss H, Flather M, et al. Nonsurgical reduction of the interventricular septum in patients with hypertrophic cardiomyopathy. N Engl J Med 2002;347:1326–33. [Retraction in: Coats AJ, Henein M, Flather M, Sigwart U, Seggewiss H, Wang D, et al. N Engl J Med 2003;348:951.] [PubMed]
3. Knight C, Kurbaan AS, Seggewiss H, Henein M, Gunning M, Harrington D, et al. Nonsurgical septal reduction for hypertrophic obstructive cardiomyopathy: outcome in the first series of patients. Circulation 1997;95:2075–81. [PubMed]
4. Seggewiss H, Gleichmann U, Faber L, Fassbender D, Schmidt HK, Strick S. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and 3-month follow-up in 25 patients. J Am Coll Cardiol 1998;31:252–8. [PubMed]
5. Seggewiss H, Faber L, Gleichmann U. Percutaneous transluminal septal ablation in hypertrophic obstructive cardiomyopathy. Thorac Cardiovasc Surg 1999;47:94–100. [PubMed]
6. Ruzyllo W, Chojnowska L, Demkow M, Witkowski A, Kus-mierczyk-Droszcz B, Piotrowski W, et al. Left ventricular out-flow tract gradient decrease with non-surgical myocardial reduction improves exercise capacity in patients with hypertrophic obstructive cardiomyopathy. Eur Heart J 2000; 21:770–7. [PubMed]
7. Lakkis NM, Nagueh SF, Dunn JK, Killip D, Spencer WH 3rd. Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up. J Am Coll Cardiol 2000;36:852–5. [PubMed]
8. Airoldi F, Di Mario C, Catanoso A, Dharmadhikari A, Tzifos V, Anzuini A, et al. Progressive decrease of outflow gradient and septum thickness after percutaneous alcoholization of the interventricular septum in hypertrophic obstructive cardiomyopathy. Ital Heart J 2000;1:200–6. [PubMed]
9. Mazur W, Nagueh SF, Lakkis NM, Middleton KJ, Killip D, Roberts R, Spencer WH 3rd. Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 2001;103:1492–6. [PubMed]
10. Bhagwandeen R, Woo A, Ross J, Wigle ED, Rakowski H, Kwinter J, et al. Septal ethanol ablation for hypertrophic obstructive cardiomyopathy: early and intermediate results of a Canadian referral centre. Can J Cardiol 2003;19:912–7. [PubMed]
11. Chang SM, Lakkis NM, Franklin J, Spencer WH 3rd, Nagueh SF. Predictors of outcome after alcohol septal ablation therapy in patients with hypertrophic obstructive cardiomyopathy. Circulation 2004;109:824–7. [PubMed]
12. Nagueh SF, Ommen SR, Lakkis NM, Killip D, Zoghbi WA, Schaff HV, et al. Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2001; 38:1701–6. [PubMed]
13. Nagueh SF, Lakkis NM, Middleton KJ, Killip D, Zoghbi WA, Quinones MA, Spencer WH 3rd. Changes in left ventricular diastolic function 6 months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 1999;99:344–7. [PubMed]
14. Seggewiss H, Rigopoulos A, Faber L, Ziemssen P. Alcohol septal ablation. In: Maron BJ, editor. Diagnosis and management of hypertrophic cardiomyopathy: sudden death prevention. Malden (MA): Blackwell Futura; 2004. p. 259–78.
15. Brugada P, de Swart H, Smeets JL, Wellens HJ. Transcoronary chemical ablation of ventricular tachycardia. Circulation 1989;79:475–82. [PubMed]
16. Autore C, Bernabo P, Barilla CS, Bruzzi P, Spirito P. The prognostic importance of left ventricular outflow obstruction in hypertrophic cardiomyopathy varies in relation to the severity of symptoms. J Am Coll Cardiol 2005;45:1076–80. [PubMed]
17. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778–85. [PubMed]
18. Firoozi S, Elliott PM, Sharma S, Murday A, Brecker SJ, Ha-mid MS, et al. Septal myotomy-myectomy and transcoronary septal alcohol ablation in hypertrophic obstructive cardiomyopathy. A comparison of clinical, haemodynamic and exercise outcomes. Eur Heart J 2002;23:1617–24. [PubMed]
19. Beahrs MM, Tajik AJ, Seward JB, Giuliani ER, McGoon DC. Hypertrophic obstructive cardiomyopathy: ten- to 21-year follow-up after partial septal myectomy. Am J Cardiol 1983;51:1160–6. [PubMed]
20. Cohn LH, Trehan H, Collins JJ Jr. Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy. Am J Cardiol 1992;70:657–60. [PubMed]
21. Mohr R, Schaff HV, Danielson GK, Puga FJ, Pluth JR, Tajik AJ. The outcome of surgical treatment of hypertrophic obstructive cardiomyopathy. Experience over 15 years. J Thorac Cardiovasc Surg 1989;97:666–74. [PubMed]
22. Schoendube FA, Klues HG, Reith S, Messmer BJ. Surgical correction of hypertrophic obstructive cardiomyopathy with combined myectomy, mobilisation and partial excision of the papillary muscles. Eur J Cardiothorac Surg 1994;8:603–8. [PubMed]
23. Heric B, Lytle BW, Miller DP, Rosenkranz ER, Lever HM, Cosgrove DM. Surgical management of hypertrophic obstructive cardiomyopathy. Early and late results. J Thorac Car-diovasc Surg 1995;110:195–208.
24. Robbins RC, Stinson EB. Long-term results of left ventricular myotomy and myectomy for obstructive hypertrophic cardiomyopathy. J Thorac Cardiovasc Surg 1996;111:586–94. [PubMed]
25. Schulte HD, Borisov K, Gams E, Gramsch-Zabel H, Losse B, Schwartzkopff B. Management of symptomatic hypertrophic obstructive cardiomyopathy–long-term results after surgical therapy. Thorac Cardiovasc Surg 1999;47:213–8. [PubMed]
26. Maron BJ, Dearani JA, Ommen SR, Maron MS, Schaff HV, Gersh BJ, Nishimura RA. The case for surgery in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 44:2044–53. [PubMed]
27. Woo A, Williams WG, Choi R, Wigle ED, Rozenblyum E, Fedwick K, et al. Clinical and echocardiographic determinants of long-term survival after surgical myectomy in obstructive hypertrophic cardiomyopathy. Circulation 2005;111:2033–41. [PubMed]
28. Elliott PM, Brecker SJ, McKenna WJ. Left ventricular opacification during selective intracoronary injection of echo-car-diographic contrast in patients with hypertrophic cardiomy-opathy. Heart 2000;83:E7. [PMC free article] [PubMed]
29. Monakier D, Horlick E, Ross J, Woo A, Rakowski H, Schwartz L, et al. Intracoronary myocardial contrast echocardiography in a patient with drug refractory hypertrophic obstructive cardiomyopathy revealing extensive myocardium at risk for in-farction with alcohol septal ablation. J Invasive Cardiol 2004; 16:482–4. [PubMed]
30. Morrow AG, Braunwald E. Functional aortic stenosis; a mal-formation characterized by resistance to left ventricular outflow without anatomic obstruction. Circulation 1959;20: 181–9. [PubMed]
31. 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. [PubMed]
32. Murgo JP, Alter BR, Dorethy JF, Altobelli SA, McGranahan GM Jr. Dynamics of left ventricular ejection in obstructive and nonobstructive hypertrophic cardiomyopathy. J Clin Invest 1980;66:1369–82. [PMC free article] [PubMed]
33. Ross J Jr, Braunwald E, Gault JH, Mason DT, Morrow AG. The mechanism of the intraventricular pressure gradient in idiopathic hypertrophic subaortic stenosis. Circulation 1966; 34:558–78. [PubMed]
34. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy (ASH): the unifying link in the IHSS disease spectrum. Observations regarding its pathogenesis, pathophysiology, and course. Circulation 1973;47:827–32. [PubMed]
35. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardiol 1995;26:1699–708. [PubMed]
36. Maron BJ, Harding AM, Spirito P, Roberts WC, Waller BF. Systolic anterior motion of the posterior mitral leaflet: a previously unrecognized cause of dynamic subaortic obstruction in patients with hypertrophic cardiomyopathy. Circulation 1983;68:282–93. [PubMed]
37. Klues HG, Roberts WC, Maron BJ. Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy. Circulation 1993;87:1570–9. [PubMed]
38. Roberts R, Sigwart U. New concepts in hypertrophic cardiomyopathies, part I. Circulation 2001;104:2113–6. [PubMed]
39. Levine RA. Echocardiographic assessment of the cardiomyopathies. In: Weyman AE, editor. Principles and practice of echocardiography. Philadelphia: Lea & Febiger; 1994. p. 798–803.
40. Burri H, Sigwart U. Alcohol septal ablation for hypertrophic obstructive cardiomyopathy. In: Hermann HC, editor. Contemporary cardiology; percutaneous noncoronary interventions. Totowa (NJ): Humana Press; 2005. p. 259–69.
41. Fulton WFM. The coronary arteries; arteriography, microanatomy, and pathogenesis of obliterative coronary artery disease. Springfield (IL): Charles C. Thomas; 1965. p. 83–8.
42. Sahni D, Jit I. Blood supply of the human interventricular septum in north-west Indians [published erratum appears in Indian Heart J 1990;42:334]. Indian Heart J 1990;42:161–9. [PubMed]
43. Angelini P, Villason S, Chan AV Jr, Diez JG. Normal and anomalous coronary arteries in humans. In: Angelini P, editor. Coronary artery anomalies: a comprehensive approach. Baltimore: Lippincott Williams & Wilkins; 1999. p. 27–150.
44. Hosseinpour AR, Anderson RH, Ho SY. The anatomy of the septal perforating arteries in normal and congenitally malformed hearts. J Thorac Cardiovasc Surg 2001;121:1046–52. [PubMed]
45. Singh M, Edwards WD, Holmes DR Jr, Tajil AJ, Nishimura RA. Anatomy of the first septal perforating artery: a study with implications for ablation therapy for hypertrophic cardiomyopathy. Mayo Clin Proc 2001;76:799–802. [PubMed]
46. Kuhn H, Gietzen F, Leuner C, Gerenkamp T. Induction of subaortic septal ischaemia to reduce obstruction in hypertrophic obstructive cardiomyopathy. Studies to develop a new catheter-based concept of treatment. Eur Heart J 1997;18:846–51. [PubMed]
47. Fifer MA, Yoerger DM, Picard MH, Vlahakes GJ, Palacios IF. Images in cardiovascular medicine. Covered stent septal ablation for hypertrophic obstructive cardiomyopathy: initial success but ultimate failure resulting from collateral formation. Circulation 2003;107:3248–9. [PubMed]
48. Iacob M, Pinte F, Tintoiu I, Cotuna L, Caroescu M, Popa A, et al. Microcoil embolisation for ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy. Kardiol Pol 2004;61:350–5. [PubMed]
49. Faber L, Seggewiss H, Gleichmann U. Percutaneous trans-luminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: results with respect to intraprocedural myocardial contrast echocardiography. Circulation 1998;98:2415–21. [PubMed]
50. Said M, Muhlberger VA. The descending septal branch (Bonapace's branch). A case report and literature review of this often forgotten branch. First description in vivo. Eur Heart J 1995;16:1443–7. [PubMed]
51. Qin JX, Shiota T, Lever HM, Asher CR, Popovic ZB, Greenberg NL, et al. Conduction system abnormalities in patients with obstructive hypertrophic cardiomyopathy following septal reduction interventions. Am J Cardiol 2004;93:171–5. [PubMed]
52. Chang SM, Nagueh SF, Spencer WH 3rd, Lakkis NM. Complete heart block: determinants and clinical impact in patients with hypertrophic obstructive cardiomyopathy undergoing nonsurgical septal reduction therapy. J Am Coll Cardiol 2003;42:296–300. [PubMed]
53. Chen AA, Palacios IF, Mela T, Yoerger DM, Picard MH, Vlahakes G, et al. Acute predictors of subacute complete heart block after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Am J Cardiol 2006;97:264–9. [PubMed]
54. Schwarz ER, Klues HG, vom Dahl J, Klein I, Krebs W, Hanrath P. Functional, angiographic and intracoronary Doppler flow characteristics in symptomatic patients with myocardial bridging: effect of short-term intravenous beta-blocker medication. J Am Coll Cardiol 1996;27:1637–45. [PubMed]
55. Raute-Kreinsen U. Morphology of necrosis and repair after transcoronary ethanol ablation of septal hypertrophy. Pathol Res Pract 2003;199:121–7. [PubMed]
56. Batalis NI, Harley RA, Collins KA. Iatrogenic deaths following treatment for hypertrophic obstructive cardiomyopathy: case reports and an approach to the autopsy and death certification. Am J Forensic Med Pathol 2005;26:343–8. [PubMed]
57. Wykrzykowska JJ, Kwaku K, Wylie J, Manning WJ, Josephson ME, Zimetbaum P, Laham RJ. Delayed occurrence of unheralded phase IV complete heart block after ethanol septal ablation for symmetric hypertrophic obstructive cardiomyopathy. Pacing Clin Electrophysiol 2006;29:674–8. [PubMed]
58. Veselka J, Duchonova R, Prochazkova S, Homolova I, Palenickova J, Zemanek D, et al. The biphasic course of changes of left ventricular outflow gradient after alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Kardiol Pol 2004;60:133–7. [PubMed]
59. Yoerger DM, Picard MH, Palacios IF, Vlahakes GJ, Lowry PA, Fifer MA. Time course of pressure gradient response after first alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Am J Cardiol 2006;97:1511–4. [PubMed]
60. Schulz-Menger J, Strohm O, Waigand J, Uhlich F, Dietz R, Friedrich MG. The value of magnetic resonance imaging of the left ventricular outflow tract in patients with hypertrophic obstructive cardiomyopathy after septal artery embolization. Circulation 2000;101:1764–6. [PubMed]
61. Franke A, Kuhl HP, Schoendube FA. MRI versus 3D echo-cardiography in postinterventional patients with hypertrophic obstructive cardiomyopathy. Circulation 2001;104:E32–3. [PubMed]
62. Amano Y, Takayama M, Amano M, Kumazaki T. MRI of cardiac morphology and function after percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy. AJR Am J Roentgenol 2004;182:523–7. [PubMed]
63. Sitges M, Qin JX, Lever HM, Bauer F, Drinko JK, Agler DA, et al. Evaluation of left ventricular outflow tract area after septal reduction in obstructive hypertrophic cardiomyopathy: a real-time 3-dimensional echocardiographic study. Am Heart J 2005;150:852–8. [PubMed]
64. Mazur W, Nagueh SF, Lakkis NM, Middleton KJ, Killip D, Roberts R, Spencer WH 3rd. Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 2001; 103:1492–6. [PubMed]
65. Lamke GT, Allen RD, Edwards WD, Tazelaar HD, Danielson GK. Surgical pathology of subaortic septal myectomy associated with hypertrophic cardiomyopathy. A study of 204 cases (1996–2000). Cardiovasc Pathol 2003;12:149–58. [PubMed]
66. Maron BJ, Shen WK, Link MS, Epstein AE, Almquist AK, Daubert JP, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000;342:365–73. [PubMed]

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