Article

Alcohol Septal Ablation for the Treatment of Hypertrophic Obstructive Cardiomyopathy

Register or Login to View PDF Permissions
Permissions× For commercial reprint enquiries please contact Springer Healthcare: ReprintsWarehouse@springernature.com.

For permissions and non-commercial reprint enquiries, please visit Copyright.com to start a request.

For author reprints, please email rob.barclay@radcliffe-group.com.

  • Views: 2386

  • Likes: 0

  • Downloads: 20

  • Citations: 2

  • Read time: 15m
Average (ratings)
No ratings
Your rating

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disorder characterised by left ventricular hypertrophy. A subgroup of patients develops limiting symptoms in association with left ventricular outflow tract obstruction (LVOTO). Current international guidelines recommend that symptomatic patients are initially treated by alleviating exacerbating factors and negatively inotropic medication. Drug-refractory symptoms require a comprehensive evaluation of the mechanism of LVOTO and review by a multidisciplinary team to consider the relative merits of myectomy, alcohol septal ablation (ASA) and pacing. This article provides a brief overview of HCM and the pathophysiology of LVOTO, and reviews the use of ASA in patients with drug-refractory symptoms secondary to LVOTO.

Keywords

Hypertrophic cardiomyopathy, outflow tract obstruction, left ventricular outflow tract obstruction, alcohol septal ablation, myectomy,

Disclosure:The authors have no conflicts of interest to declare.

Received:

Accepted:

DOI:https://doi.org/10.15420/icr.2011.9.2.108

Correspondence Details:Charles Knight, The Heart Muscle Disease Clinic, London Chest Hospital, Bonner Road, London E2 9JX, UK. E: Charles.Knight@bartshealth.nhs.uk

Copyright Statement:

The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder of cardiac muscle with a heterogeneous clinical course.1 The disease is clinically characterised by left ventricular hypertrophy (LVH), which is typically asymmetric, and a subgroup of patients have left ventricular outflow tract obstruction (LVOTO) caused by systolic anterior motion (SAM) of the mitral valve leaflet(s).2,3 LVOTO is often associated with limiting cardiovascular symptoms and a worse prognosis.4–8

This article provides a brief overview of HCM and the pathophysiology of LVOTO, and reviews the use of alcohol septal ablation (ASA) for the treatment drug-refractory symptoms secondary to LVOTO.

Hypertrophic Cardiomyopathy Diagnostic Criteria
HCM is defined by the presence of LVH (left ventricular wall thickness ≥15 mm in a single myocardial segment) in the absence of systemic hypertension, congenital heart disease and valve lesions of sufficient severity to explain the observed degree of hypertrophy.1,9 In first-degree relatives who have inherited a disease-causing mutation, lesser degrees of LVH are sufficient to make the diagnosis.10,11 The diagnosis is reached by integrating clinical and imaging data from echocardiography and increasingly cardiac magnetic resonance (CMR) imaging.

Epidemiology
The prevalence of HCM ranges from 0.02 % to 0.23 %, depending on the characteristics of the study population and methodology used.12–20

Aetiology
In adults, HCM is primarily inherited in an autosomal dominant manner and is caused by mutations in cardiac sarcomere protein genes.21–23 Mutations in these genes can be found in ~60 % of patients with HCM,21–23 and the majority involve cardiac myosin binding protein-C (MYBPC3) and cardiac myosin heavy chain (MYH7).24 There is a poor correlation between genotype and phenotype.25,26

Metabolic diseases (e.g. Anderson-Fabry disease), syndromes (e.g. Noonan) and amyloid can mimic sarcomeric HCM.1,27 Phenocopies may be recognised by the presence of specific phenotypic ‘red flags’ (e.g. conduction disease in Anderson-Fabry disease), which help rational selection of diagnostic tests and ultimately disease-specific treatments (e.g. enzyme replacement therapy for Anderson-Fabry disease).27

Left Ventricular Outflow Tract Obstruction
LVOTO at rest is encountered in ~30 % of patients with HCM, and is associated with limiting symptoms (dyspnoea, angina, syncope) and worse prognosis.4–8 Unlike symptom limitation from ischaemic heart disease and left ventricular systolic dysfunction, effort tolerance in obstructive HCM is often variable, and patients often describe both good and bad days; this may make assessments of functional class (for example using the New York Heart Association [NYHA] classification) challenging. Approximately a third of HCM patients report postprandial exacerbation of symptoms.28

LVOTO is caused by the SAM of the mitral valve. In systole, the anterior mitral valve leaflet moves into the left ventricular outflow tract (LVOT), which is already narrowed by the hypertrophied septum creating a physical barrier, which impedes the flow of blood from the ventricle to the aorta during systole (see Figure 1).2,3 Contact of the mitral valve leaflets to the septum is termed ‘complete’ SAM, and lesser forms of SAM where there is no contact are termed ‘incomplete’. SAM of the mitral valve leaflets is often associated with varying degrees of mitral regurgitation since the two mitral valve leaflets are pulled apart during SAM, creating an orifice through which retrograde, posteriorly-directed flow in the left atrium can occur. Consequently, conditions which increase LVOTO also increase the severity of mitral regurgitation.3,29 LVOTO is also promoted by coincident abnormalities of the mitral valve leaflets. The leaflets (particularly the anterior leaflet) are frequently elongated and displaced anteriorly, with abnormal attachments to the papillary muscles and chordae.30,31 Early investigators attributed SAM of the mitral valve to suction forces (Venturi effect) caused by accelerating blood flow in LVOT during systole, drawing the mitral valve leaflets anteriorly into the outflow tract. However, SAM of the mitral valve commences in early systole when the Venturi effect is minimal, and this is therefore unlikely to be the sole explanation for LVOTO.32,33 The mechanism underlying LVOTO is probably multi-factorial, involving the interaction of abnormalities of papillary muscles, chordae, mitral leaflets and LVH, which culminate in abnormal flow forces that push and/or pull the mitral valve towards the outflow septum.33 Although LVOTO gradient is the most evident abnormality, the physiology of obstructive disease includes elevated left ventricular (LV) end-diastolic pressure, mitral regurgitation and a potential for abrupt changes in LVOTO magnitude (for example with postural change or sudden exertion); these abnormalities, as well as the increased LV afterload, may all contribute to symptoms.

A characteristic feature of LVOTO is that the severity of the obstruction is dynamic and subject to prevailing haemodynamic conditions. LVOTO is exacerbated by conditions causing reduced preload (e.g. Valsalva, squat to stand), reduced afterload (e.g. vasodilators) or positive inotropes.3 Notably, although LVOTO is most often seen in HCM, it may also occur in other conditions or physiological states and is not pathognomonic of HCM.34,35 In a smaller subgroup of HCM patients, obstruction can develop at the mid-left ventricular cavity. Mid-cavity obstruction is caused by the systolic apposition of hypertrophied mid-ventricular segments and/or papillary muscles creating a characteristic hour-glass appearance with a distinct apical cavity.36,37 This form of obstruction is often associated with apical aneurysm formation.36,37 Mid-cavity obstruction can exist in isolation (see Figure 2) or in conjunction with LVOTO. Even though ASA has been used in the treatment of mid-cavity obstruction,38,39 this is not routine practice and further discussion is beyond the scope of this review.

Assessment of Left Ventricular Outflow Tract Obstruction
All patients with HCM should undergo a detailed transthoracic echocardiogram to examine:

  • the severity and distribution of hypertrophy and in particular the septal wall thickness at the point of mitral-septal contact;
  • intra-cavity gradients with continuous and pulsed-wave Doppler to determine the severity and level of obstruction (LVOTO, mid-cavity obstruction or both);
  • the mitral valve apparatus for systolic anterior movement of the mitral valve, hypertrophied papillary muscles, abnormal chordal attachments and intrinsic mitral valve disease; and
  • other cardiac pathology that may have an impact on treatment (e.g. aortic valve disease).

If the transthoracic echocardiogram fails to provide the necessary diagnostic information, a transoesophageal echocardiogram, CMR or an invasive haemodynamic study may be required.

Left Ventricular Outflow Tract Obstruction
Download original

An instantaneous Doppler LVOT gradient of ≥30 mmHg is considered significant, and such patients are classified as having the obstructive form of the disease. However, LVOTO is considered to be haemodynamically significant only when the LVOT gradient is ≥50 mmHg.3 There are few data to support these thresholds,3 which are largely empirically defined and reflect an understanding that when LVOTO is mild, therapeutic reduction of LVOTO is less likely to improve symptoms, and alternative causes of severe symptoms should be sought.

Isolated Mid-cavity Obstruction
Download original
Treatment of Algorithm for Symptomatic
Download original

Alcohol Septal Ablation
Download original

Since LVOTO is dynamic, obstruction may not be apparent in the supine patient under resting conditions. Exercise, the Valsalva manoeuvre, postural changes or an isoprenaline infusion help demonstrate latent LVOTO.6,40–42 These additional tests are mandatory in the evaluation of patients with symptoms suggestive of obstruction, which is not demonstrable at rest.

Treatment of Symptomatic Left Ventricular Outflow Tract Obstruction
Currently, there is no evidence that asymptomatic patients with LVOTO benefit from treatment to reduce the severity of obstruction; treatment is reserved for patients with LVOTO and drug-refractory symptoms.43,44 A contemporary treatment algorithm for symptomatic patients with LVOTO is summarised in Figure 3. The first-line treatment for symptoms associated with LVOTO is correction of exacerbating factors (e.g. vasodilating antihypertensives, anaemia) followed by pharmacological therapy with β-blockers, verapamil and disopyramide, which modulate the dynamic physiology of obstruction through their negative inotropic and chronotropic effects.43–46 In patients with drug-refractory symptoms or unacceptable side effects, invasive treatments should be considered by a multidisciplinary team following a comprehensive evaluation of the mechanism of obstruction:

  • Surgical myectomy involves excision of the hypertrophied septum at the point of mitral contact through an aortotomy under cardiopulmonary bypass.47 Surgical myectomy is a technically demanding operation, but with improved peri-operative care and surgical techniques the current peri-operative mortality is low in high volume centres. In addition to the general complications of open heart surgery, specific peri-operative complications of myectomy include ventricular septal defects, aortic regurgitation and complete heart block requiring pacemaker implantation.48,49
  • Mitral valve repair/replacement may be required as an adjunct to myectomy.50–52 Mitral valve replacement in isolation also abolishes SAM and LVOTO, but is considered only when there are other indications for valve replacement such as intrinsic mitral valve disease.53,54
  • Alcohol septal ablation aims to reproduce the effects of myectomy via a minimally invasive percutaneous approach.55,56 Ethanol is injected via the septal perforator branches of the left anterior descending artery to the hypertrophied septum to induce a myocardial infarction and necrosis. Scar formation causes remodelling of the LVOT with relief of obstruction. ASA is discussed in more detail below.
  • Atrioventricular (AV) sequential pacing from the right ventricular apex using dual-chamber pacemakers with short AV delay reduces LVOTO by causing septal dysynchrony and modifying preload.57 Placebo-controlled trials showed an improvement in symptoms but with a less consistent reduction in LVOTO.58–62

ASA is currently the most frequently used invasive therapy, and while it is efficacious, relatively safe and minimally invasive, outcomes from randomised trials comparing different invasive techniques are not yet available. Several experienced opinions still regard surgical treatment as the ‘gold standard’.43,44 Currently, patients must be counselled that choices between ASA, surgery and pacing are made on the basis of considerations other than proven differences in outcome.

In general, ASA may be unsuitable in the presence of co-existing mid-cavity obstruction and/or intrinsic mitral valve disease; in such cases a surgical approach should be considered. Septal reduction either by ASA or myectomy when the septal wall thickness is <15 mm at the site of mitral contact is also challenging, and alternatives such as mitral valve repair/replacement or AV sequential pacing should be considered. AV sequential pacing can also be useful in selected patients where aggressive pharmacological treatment with a β-blocker, verapamil and disopyramide is contemplated, and in patients too frail to tolerate more invasive treatment. In others, pacing may be considered as an initial therapeutic trial before progression to more invasive treatment. This may include individuals with conventional indicators for device therapy (including pacing and defibrillator treatment) and patients at high risk of developing heart block following invasive treatment. Patient preference is also a key factor in decision-making.

Alcohol Septal Ablation – Procedural Aspects
The essential components of this percutaneous procedure include the identification of an appropriate septal perforator artery, its isolation from the rest of the coronary circulation and the selective injection of alcohol into this artery. The first septal artery is usually selected and a short over-the-wire balloon inflated within the artery. The balloon’s lumen allows selective delivery of angiographic contrast, echo contrast and ultimately, alcohol into the septal artery. Angiographic contrast ensures that the septal artery is isolated from the left anterior descending (LAD) by the inflated balloon, and echo contrast confirms that the myocardial volume subtended by the selected septal artery is an appropriate target for ablation.63–65 The proximal septal vessels may also supply the right ventricular free wall, LV apex and papillary muscles, and several echocardiographic views are needed to ensure contrast enhancement is confined to the target area; the appropriate target lies adjacent to the point of mitral-septal contact. If echo contrast does not localise to the target area, other septal arteries should be selectively assessed. A temporary pacing wire is inserted prior to the injection of alcohol in case significant bradyarrhythmias follow conduction system damage. Right bundle branch block is observed in approximately 50 % of cases.66 Adequate analgesia is provided and the alcohol is slowly injected to chemically ablate and infarct the target myocardium.67 Approximately 0.1 ml of ethanol (concentration >95 %) per 1 mm of thickness of the target myocardium is injected slowly (1 ml/minute).64 The balloon remains inflated for 5–10 minutes postethanol injection to prevent reflux in the anterior descending and to enhance delivery at the target myocardium. LVOTO is often reduced or abolished at the end of the procedure; this acute effect reflects septal stunning, and the LVOT gradient may again increase in the days following the procedure, to fall again over a period of weeks as septal remodelling occurs and a small scar develops in place of the ablated myocardium. The femoral or radial approach can be used.68 Important procedural steps are shown in Figure 4.

Acute Complications of Alcohol Septal Ablation
Since its inception in 1995,55 ASA has evolved and the routine use of echo contrast to select the target septal artery has made the procedure safer and more effective.63–65 In addition to complications arising from the injection of alcohol, ASA is also associated with the complications of percutaneous coronary intervention and temporary wire insertion:

  1. Vascular injury and haemorrhage.
  2. Coronary dissection from guide catheter, wire and over-the-wire balloon manipulation.69,70
  3. Myocardial infarction from alcohol escaping from the septal branch into the LAD56 or via septal collaterals.71
  4. Cerebrovascular accidents.
  5. Cardiac tamponade from temporary wire insertion.72Sustained ventricular arrhythmias.73
  6. Complete heart block requiring pacemaker implantation (~11 %).74

Meta-analyses Examining Mortality Following Septal Reduction Therapy
Download original
Meta-analyses Examining Symptoms, Gradients and Need
Download original

Despite these potential complications, ASA remains a relatively safe procedure with in-hospital death rates of around 1 %.69,75

Post-operative Care
Patients should have a temporary pacing wire in situ with cardiac monitoring for 24–48 hours after the procedure, as they are at risk of arrhythmias. High-grade AV block resolves in the majority of cases within three days.76 On discharge, patients should be advised to report arrhythmic symptoms as rarely new onset bradyarrhythmias develop late after the procedure.77 Cardiac biomarkers peak at 12 hours post-ASA and correlate with the size of myocardial injury.78 In the absence of new conduction abnormalities, pharmacotherapy for symptomatic LVOTO should continue until a clinical review in 3–6 months, and can then be tapered if symptoms have improved.

Long and Medium-term Outcomes– Alcohol Septal Ablation Versus Myectomy
Mortality associated with ASA and surgical myectomy has been examined and compared in four meta-analyses.74,79–81 Even though the meta-analyses included individual studies with very different inclusion criteria, they have consistently shown that the two procedures have similar survival outcomes (see Table 1). Both septal reduction therapies achieve similar improvements in symptoms, which is the principal aim of invasive therapy. However, myectomy is associated with a greater reduction in gradients and reduced need for post-procedural anti-bradycardia pacing (see Table 2).74,79–81 Concerns over the long term arrhythmogenic potential of the myocardial scar induced by alcohol septal ablation67 are not supported by observational data of implantable cardioverter defibrillator (ICD) recipients undergoing the procedure82 or mortality data from the meta-analyses.74,79– 81

Procedural Failure
ASA is effective at reducing symptoms in more than 85 % of patients.69 In cases of procedural failure, defined by the persistence of both symptoms and LVOTO (rest or latent), further intervention with any of the modalities may be considered following a repeat assessment of the mechanisms responsible for symptoms. As changes in LV morphology following ASA may be delayed, it is prudent to delay decisions regarding further intervention for 3–6 months.83

Significant symptoms may persist in about 10–20 % of patients despite LVOTO abolition, illustrating the importance of the complexity of the disease and appropriate patient selection. It is therefore important to counsel patients that LVOTO reduction does not cure HCM and ongoing care will be required to monitor and treat their disease.

Alternative Percutaneous Septal Reduction Therapies
Alternative approaches to reduce hypertrophy at the point of mitral-septal contact by means other than alcohol have been investigated:

  • Microcoils, polyvinyl alcohol foam and cyanoacrylate glue delivered in the target septal artery obstruct the vessel with infarction of the subtended myocardium.84–87
  • Direct endocavitary radiofrequency or cryotherapy ventricular ablation.88,89This approach has the advantage of overcoming unfavourable septal anatomy.

Experience with these alternatives is limited and long-term safety data are not available.

Care Beyond Left Ventricular Outflow Tract Obstruction
LVOTO should not overshadow other aspects of management; patients in whom LVOTO is successfully abolished are still subject to other HCM-related risks and outcomes. HCM should be evaluated in units with relevant expertise to address family screening and genetic testing, the risk of sudden cardiac death, atrial arrhythmias and prevention of stroke.

Conclusion
LVOTO is associated with significant morbidity and mortality. In patients with LVOTO and drug-refractory symptoms, invasive treatment should be considered following a multidisciplinary team review. The choice of invasive therapy depends not only on disease-specific characteristics but also patient preference. Contrast echocardiography-guided ASA is a safe and effective modality, which will improve symptoms in the majority of patients.

References

  1. Elliott P, Andersson B, Arbustini E, et al., Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases, Eur Heart J, 2008;29:270–6.
    Crossref | PubMed
  2. 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.
    Crossref | PubMed
  3. Wigle ED, Sasson Z, Henderson MA, et al., Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review, Prog Cardiovasc Dis, 1985;28:1–83.
    Crossref | PubMed
  4. Maron MS, Olivotto I, Betocchi S, et al., Effect of Left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy, N Engl J Med, 2003;348:295–303.
    Crossref | PubMed
  5. Autore C, Bernabò P, Barillà CS, et al., 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.
    Crossref | PubMed
  6. Maron MS, Olivotto I, Zenovich AG, et al., Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction, Circulation, 2006;114:2232–9.
    Crossref | PubMed
  7. Elliott PM, Gimeno JR, Tomé MT, et al., Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy, Eur Heart J, 2006;27:1933–41.
    Crossref | PubMed
  8. O’Mahony C, Jichi F, Pavlou M, et al., A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD), Eur Heart J, 2013 [Epub ahead of print].
    Crossref | PubMed
  9. Henry WL, Gardin JM, Ware JH, Echocardiographic measurements in normal subjects from infancy to old age, Circulation, 1980;62:1054–61.
    Crossref | PubMed
  10. McKenna WJ, Spirito P, Desnos M, et al., Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families, Heart, 1997;77:130–2.
    Crossref | PubMed
  11. Charron P, Forissier JF, Amara ME, et al., Accuracy of European diagnostic criteria for familial hypertrophic cardiomyopathy in a genotyped population, Int J Cardiol, 2003;90:33–8.
    Crossref | PubMed
  12. Hada Y, Sakamoto T, Amano K, et al., Prevalence of hypertrophic cardiomyopathy in a population of adult Japanese workers as detected by echocardiographic screening, Am J Cardiol, 1987;59:183–4.
    Crossref | PubMed
  13. Maron BJ, Gardin JM, Flack JM, et al., 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;92:785–9.
    Crossref | PubMed
  14. Corrado D, Basso C, Schiavon M, Thiene G, Screening for hypertrophic cardiomyopathy in young athletes, N Engl J Med, 1998;339:364–9.
    Crossref | PubMed
  15. Maron BJ, Mathenge R, Casey SA, et al., Clinical profile of hypertrophic cardiomyopathy identified de novo in rural communities, J Am Coll Cardiol, 1999;33:1590–5.
    Crossref | PubMed
  16. Nistri S, Thiene G, Basso C, et al., Screening for hypertrophic cardiomyopathy in a young male military population, Am J Cardiol, 2003;91:1021–3, A8.
    Crossref | PubMed
  17. Zou Y, Song L, Wang Z, et al., Prevalence of idiopathic hypertrophic cardiomyopathy in China: a population-based echocardiographic analysis of 8080 adults, Am J Med, 2004;116:14–8.
    Crossref | PubMed
  18. Maron BJ, Spirito P, Roman MJ, et al., Prevalence of hypertrophic cardiomyopathy in a population-based sample of American Indians aged 51 to 77 years (the Strong Heart Study), Am J Cardiol, 2004;93:1510–4.
    Crossref | PubMed
  19. Maro EE, Janabi M, Kaushik R, Clinical and echocardiographic study of hypertrophic cardiomyopathy in Tanzania, Trop Doct, 2006;36:225–7.
    Crossref | PubMed
  20. Ng CT, Chee TS, Ling LF, et al., Prevalence of hypertrophic cardiomyopathy on an electrocardiogram-based preparticipation screening programme in a young male South- East Asian population: results from the Singapore Armed Forces Electrocardiogram and Echocardiogram screening protocol, Europace, 2011;13:883–8.
    Crossref
  21. Van Driest SL, Ommen SR, Tajik AJ, et al., Yield of genetic testing in hypertrophic cardiomyopathy, Mayo Clin Proc, 2005;80:739–44.
    Crossref | PubMed
  22. Morita H, Rehm HL, Menesses A, et al., Shared genetic causes of cardiac hypertrophy in children and adults, N Engl J Med, 2008;358:1899–908.
    Crossref | PubMed
  23. Brito D, Miltenberger-Miltenyi G, Vale Pereira S, et al., Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population, Rev Port Cardiol, 2012;31:577–87.
    Crossref | PubMed
  24. Richard P, Charron P, Carrier L, et al., Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy, Circulation, 2003;107:2227–32.
    Crossref
  25. Watkins H, McKenna WJ, Thierfelder L, et al., Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy, N Engl J Med, 1995;332:1058–64.
    Crossref | PubMed
  26. Pasquale F, Syrris P, Kaski JP, et al., Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene, Circ Cardiovasc Genet, 2012;5:10–7.
    Crossref | PubMed
  27. Rapezzi C, Arbustini E, Caforio AL, et al., Diagnostic workup in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases, Eur Heart J, 2013;34:1448–58.
    Crossref
  28. Gilligan DM, Nihoyannopoulos P, Fletcher A, et al., Symptoms of hypertrophic cardiomyopathy, with special emphasis on syncope and postprandial exacerbation of symptoms, Clin Cardiol, 1996;19:371–8.
    Crossref | PubMed
  29. Wigle E, The diagnosis of hypertrophic cardiomyopathy, Heart, 2001;86:709–14.
    Crossref | PubMed
  30. Klues HG, Maron BJ, Dollar AL, Roberts WC, Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy, Circulation, 1992;85:1651–60.
    Crossref | PubMed
  31. Levine RA, Vlahakes GJ, Lefebvre X, et al., Papillary muscle displacement causes systolic anterior motion of the mitral valve. Experimental validation and insights into the mechanism of subaortic obstruction, Circulation, 1995;91:1189–95.
    Crossref | PubMed
  32. Sherrid MV, Gunsburg DZ, Moldenhauer S, Pearle G, Systolic anterior motion begins at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy, J Am Coll Cardiol, 2000;36:1344–54.
    Crossref | PubMed
  33. Jiang L, Levine RA, King ME, Weyman AE, An integrated mechanism for systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy based on echocardiographic observations, Am Heart J, 1987;113:633–44.
    Crossref | PubMed
  34. Cabrera-Bueno F, Garcia-Pinilla JM, Gómez-Doblas JJ, et al., Beta-blocker therapy for dynamic left ventricular outflow tract obstruction induced by exercise, Int J Cardiol, 2007;117:222–6.
    Crossref | PubMed
  35. Brown JM, Murtha W, Fraser J, Khoury V, Dynamic left ventricular outflow tract obstruction in critically ill patients, Crit Care Resusc, 2002;4:170–2.
    Crossref | PubMed
  36. Efthimiadis GK, Pagourelias ED, Parcharidou D, et al., Clinical characteristics and natural history of hypertrophic cardiomyopathy with midventricular obstruction, Circ J, 2013;77:2366–74.
    Crossref | PubMed
  37. Minami Y, Kajimoto K, Terajima Y, et al., Clinical implications of midventricular obstruction in patients with hypertrophic cardiomyopathy, J Am Coll Cardiol, 2011;57:2346–55.
    Crossref | PubMed
  38. Seggewiss H, Faber L, Percutaneous septal ablation for hypertrophic cardiomyopathy and mid-ventricular obstruction, Eur J Echocardiogr, 2000;1:277–80.
    Crossref | PubMed
  39. Tengiz I, Ercan E, Alioglu E, et al., Percutaneous septal ablation for left mid-ventricular obstructive hypertrophic cardiomyopathy: a case report, BMC Cardiovasc Disord, 2006;6:15.
    Crossref | PubMed
  40. Dimitrow PP, Bober M, Michalowska J, Sorysz D, Left ventricular outflow tract gradient provoked by upright position or exercise in treated patients with hypertrophic cardiomyopathy without obstruction at rest, Echocardiography, 2009;26:513–20.
    Crossref | PubMed
  41. Shah JS, Esteban MT, Thaman R, et al., Prevalence of exercise-induced left ventricular outflow tract obstruction in symptomatic patients with non-obstructive hypertrophic cardiomyopathy, Heart, 2008;94:1288–94.
    Crossref | PubMed
  42. Vaglio JC Jr, Ommen SR, Nishimura RA, et al., Clinical characteristics and outcomes of patients with hypertrophic cardiomyopathy with latent obstruction, Am Heart J, 2008;156:342–7.
    Crossref | PubMed
  43. Maron BJ, McKenna WJ, Danielson GK, et al., American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines, Eur Heart J, 2003;24:1965–91.
    Crossref
  44. Gersh BJ, Maron BJ, Bonow RO, et al., 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons, J Am Coll Cardiol, 2011;58:e212–60.
    Crossref | PubMed
  45. Sherrid MV, Pearle G, Gunsburg DZ, Mechanism of benefit of negative inotropes in obstructive hypertrophic cardiomyopathy, Circulation, 1998;97:41–7.
    Crossref | PubMed
  46. Sherrid MV, Shetty A, Winson G, et al., Treatment of obstructive hypertrophic cardiomyopathy symptoms and gradient resistant to first-line therapy with beta-blockade or verapamil, Circ Heart Fail, 2013;6:694–702.
    Crossref | PubMed
  47. Morrow AG, Reitz BA, Epstein SE, et al., Operative treatment in hypertrophic subaortic stenosis. Techniques, and the results of pre and postoperative assessments in 83 patients, Circulation, 1975;52:88–102.
    Crossref | PubMed
  48. Dearani JA, Ommen SR, Gersh BJ, et al., Surgery insight: Septal myectomy for obstructive hypertrophic cardiomyopathy--the Mayo Clinic experience, Nat Clin Pract Cardiovasc Med, 2007;4:503–12.
    Crossref | PubMed
  49. Smedira NG, Lytle BW, Lever HM, et al., Current effectiveness and risks of isolated septal myectomy for hypertrophic obstructive cardiomyopathy, Ann Thorac Surg, 2008;85:127–33.
    Crossref | PubMed
  50. Kwon DH, Smedira NG, Thamilarasan M, et al., Characteristics and surgical outcomes of symptomatic patients with hypertrophic cardiomyopathy with abnormal papillary muscle morphology undergoing papillary muscle reorientation, J Thorac Cardiovasc Surg, 2010;140:317–24.
    Crossref | PubMed
  51. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013.
    Crossref | PubMed
  52. De Bruyne B, Sarma J. Fractional flow reserve: A review: Invasive imaging. Heart 2008;94:949–59.
    Crossref | PubMed
  53. Melikian N, De Bondt P, Tonino P, et al. Fractional flow reserve and myocardial perfusion imaging in patients with angiographic multivessel coronary artery disease. JACC Cardiovasc Interv 2010;3:307–14.
    Crossref | PubMed
  54. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213–24.
    Crossref | PubMed
  55. Fearon WF, Bornschein B, Tonino PA, et al. Economic evaluation of fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. Circulation 2010;122:2545–50.
    Crossref | PubMed
  56. Pijls NH, van Schaardenburgh P, Manoharan G, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the defer study. J Am Coll Cardiol 2007;49:2105–11.
    Crossref | PubMed
  57. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided pci versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991–1001.
    Crossref | PubMed
  58. Smits P, Thien T. Effects of adenosine on human coronary arterial circulation. Circulation 1991;84:2208–10.
    Crossref | PubMed
  59. Kern MJ, Deligonul U, Tatineni S, et al. Intravenous adenosine: Continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease. J Am Coll Cardiol 1991;18:718–29.
    Crossref | PubMed
  60. Katritsis DG, Ioannidis JP. Pci for stable coronary disease. N Engl J Med 2007;357:414–5; author reply 417–8. PubMed
  61. Kim HJ, Vignon-Clementel IE, Coogan JS, et al. Patient-specific modeling of blood flow and pressure in human coronary arteries. Ann Biomed Eng 2010;38:3195–209.
    Crossref | PubMed
  62. Taylor CA, Fonte TA, Min JK. Computational fluid dynamics applied to cardiac ct for noninvasive quantification of fractional flow reserve: Scientific basis. J Am Coll Cardiol 2013.
    Crossref | PubMed
  63. Meijs MF, Cramer MJ, El Aidi H, Doevendans PA. Ct fractional flow reserve: The next level in non-invasive cardiac imaging. Neth Heart J 2012;20:410–8.
    Crossref | PubMed
  64. Johnston BM, Johnston PR, Corney S, Kilpatrick D. Non-newtonian blood flow in human right coronary arteries: Steady state simulations. J Biomech 2004;37:709–20.
    Crossref | PubMed
  65. Johnston BM, Johnston PR, Corney S, Kilpatrick D. Nonnewtonian blood flow in human right coronary arteries: Transient simulations. J Biomech 2006;39:1116–28.
    Crossref | PubMed
  66. Morris PD, Ryan D, Morton AC, et al. Virtual fractional flow reserve from coronary angiography: Modeling the significance of coronary lesions: Results from the virtu-1 (virtual fractional flow reserve from coronary angiography) study. JACC Cardiovasc Interv 2013;6:149–57.
    Crossref | PubMed
  67. Bourantas CV, Kourtis IC, Plissiti ME, et al. A method for 3d reconstruction of coronary arteries using biplane angiography and intravascular ultrasound images. Comput Med Imaging Graph 2005;29:597–606.
    Crossref | PubMed
  68. Kousera CA, Nijjer S, Torii R, et al. Patient-specific coronary stenoses can be modeled using a combination of oct and flow velocities to accurately predict hyperemic pressure gradients. IEEE Trans Biomed Eng 2014;61:1902–13.
    Crossref | PubMed
  69. Tu S, Barbato E, Koszegi Z, et al. Fractional flow reserve calculation from 3-dimensional quantitative coronary angiography and timi frame count: A fast computer model to quantify the functional significance of moderately obstructed coronary arteries. JACC Cardiovasc Interv 2014;7:768–77.
    Crossref | PubMed
  70. Koo BK, Erglis A, Doh JH, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter discover-flow (diagnosis of ischemia-causing stenoses obtained via noninvasive fractional flow reserve) study. J Am Coll Cardiol 2011;58:1989–97.
    Crossref | PubMed
  71. Min JK, Leipsic J, Pencina MJ, et al. Diagnostic accuracy of fractional flow reserve from anatomic ct angiography. JAMA 2012;308:1237–45.
    Crossref | PubMed
  72. Katritsis D, Kaiktsis L, Chaniotis A, et al. Wall shear stress: Theoretical considerations and methods of measurement. Prog Cardiovasc Dis 2007;49:307–29.
    Crossref | PubMed
  73. Westerhof N, Lankhaar JW, Westerhof BE. The arterial windkessel. Med Biol Eng Comput 2009;47:131–41.
    Crossref | PubMed
  74. Berne R, Levy M. Cardiovasular physiology St. Louis, USA: Mosby inc. 2001.
     
  75. Matsuo S, Tsuruta M, Hayano M, et al. Phasic coronary artery flow velocity determined by doppler flowmeter catheter in aortic stenosis and aortic regurgitation. Am J Cardiol 1988;62:917–22.
    Crossref | PubMed
  76. Yoon YE, Choi JH, Kim JH, et al. Noninvasive diagnosis of ischemia-causing coronary stenosis using ct angiography: Diagnostic value of transluminal attenuation gradient and fractional flow reserve computed from coronary ct angiography compared to invasively measured fractional flow reserve. JACC Cardiovasc Imaging 2012;5:1088–96.
    Crossref | PubMed
  77. Min JK, Berman DS, Budoff MJ, et al. Rationale and design of the defacto (determination of fractional flow reserve by anatomic computed tomographic angiography) study. J Cardiovasc Comput Tomogr 2011;5:301–9.
    Crossref | PubMed
  78. Norgaard BL, Leipsic J, Gaur S, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: The nxt trial (analysis of coronary blood flow using ct angiography: Next steps). J Am Coll Cardiol 2014;63:1145–55.
    Crossref | PubMed
  79. Kim KH, Doh JH, Koo BK, et al. A novel noninvasive technology for treatment planning using virtual coronary stenting and computed tomography-derived computed fractional flow reserve. JACC Cardiovasc Interv 2014;7:72–8.
    Crossref | PubMed
  80. Min JK, Shaw LJ, Berman DS. The present state of coronary computed tomography angiography a process in evolution. J Am Coll Cardiol 2010;55:957–65.
    Crossref | PubMed
  81. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: Results from the prospective multicenter accuracy (assessment by coronary computed tomographic angiography of individuals undergoing invasive coronary angiography) trial. J Am Coll Cardiol 2008;52:1724–32.
    PubMed
  82. Miller JM, Rochitte CE, Dewey M, et al. Diagnostic performance of coronary angiography by 64-row ct. N Engl J Med 2008;359:2324–36.
    Crossref | PubMed
  83. Meijboom WB, Meijs MF, Schuijf JD, et al. Diagnostic accuracy of 64-slice computed tomography coronary angiography: A prospective, multicenter, multivendor study. J Am Coll Cardiol 2008;52:2135–44.
    PubMed
  84. Meijboom WB, Van Mieghem CA, van Pelt N, et al. Comprehensive assessment of coronary artery stenoses: Computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina. J Am Coll Cardiol 2008;52:636–43.
    Crossref | PubMed
  85. Lauer MS. Ct angiography: First things first. Circ Cardiovasc Imaging 2009;2:1–3.
    PubMed
  86. Redberg RF, Walsh J. Pay now, benefits may follow-the case of cardiac computed tomographic angiography. N Engl J Med 2008;359:2309–11.
    PubMed
  87. Serruys PW, Girasis C, Papadopoulou SL, Onuma Y. Noninvasive fractional flow reserve: Scientific basis, methods and perspectives. EuroIntervention 2012;8:511–9.
    PubMed
  88. Rajani R, Wang Y, Uss A, et al. Virtual fractional flow reserve by coronary computed tomography - hope or hype? EuroIntervention 2013;9:277–84.
    Crossref | PubMed
Previous Volume Article Next Volume Article