HCM Research Foundation Abstracts

Reflections of Inflection in Hypertrophic Cardiomyopathy.

Sherrid MV, Wever-Pinzon O, Shah A, Chaudhry FA

Journal of the American College of Cardiology 2009;54:212-219.

The shape of Doppler velocity tracings in obstructive hypertrophic cardiomyopathy offers insights into its pathophysiology. Inflection points are the points on a curve where its shape changes from concave to convex, or vice versa. These dynamic systolic abnormalities are caused: 1) by the amplifying nature of the obstruction; and 2) by the adverse effect of the sudden imposition of afterload in midsystole. The midsystolic drop in left ventricular ejection velocities and the premature termination of longitudinal shortening are compelling evidence of the deleterious mechanical effect of obstruction on the ventricle. This dynamic systolic dysfunction, demonstrated on the Doppler curves, may contribute to heart failure symptoms and adverse outcome. In outflow obstruction, these abnormalities normalize after abolition of gradient. Therefore, their detection in an individual patient confirms obstruction as a therapeutic target.

Synergistic effect of dual chamber pacing and disopyramide in obstructive hypertrophic cardiomyopathy.

Minami Y, Kajimoto K, Kawana M, Hagiwara N, Sherrid MV.
Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan.

Int J Cardiol. 2008 Dec 19.
This study examines acute effect of dual-chamber (DDD) pacing combined with disopyramide for left ventricular outflow tract (LVOT) gradient reduction in obstructive hypertrophic cardiomyopathy (HCM) patients. Among 24 patients refractory to maximal drug therapy, 7 had a significant improvement of LVOT gradient by DDD pacing alone. In the remaining 17 patients, the LVOT gradient reduction was 26+/-19% after DDD pacing alone and 35+/-16% after intravenous disopyramide alone. In contrast, after the combined therapy of DDD pacing and disopyramide, pressure gradient decreased from 102+/-35 to 28+/-23 mm Hg, a reduction of 72+/-21%. We have demonstrated synergy between DDD pacing and disopyramide for LVOT gradient reduction in obstructive HCM. Study of the long-term effects of this combined therapy would be the next step to ascertain clinical utility.

Hypertrophic cardiomyopathy: individualized therapy for a heterogeneous disease.

Sherrid MV, Sirak T.

Minerva Cardioangiol. 2008 Dec;56(6):671-92.

Hypertrophic Cardiomyopathy Program and the Echocardiography Laboratory Division of Cardiology, Department of Medicine St. Luke's, Roosevelt Hospital Center Columbia University College of Physicians and Surgeons New York City, NY, USA. msherrid@chpnet.org
It is now 50 years since the modern description of hypertrophic cardiomyopathy (HCM). The initial descriptions foretold the current efforts towards sudden death prevention, alleviation of heart failure symptoms and angina, relief of left ventricular outflow tract obstruction, preparticipation athletic screening, family screening and genetic testing. The authors review the salient features of HCM, focusing on therapeutic strategies to manage its symptoms and attempts to prevent sudden death.

Resection-plication-release for hypertrophic cardiomyopathy: clinical and echocardiographic follow-up

Balaram SK, Tyrie L, Sherrid MV, Afthinos J, Hillel Z, Winson G, Swistel DG.

Ann Thorac Surg. 2008 Nov;86(5):1539-44; discussion 1544-5.

Division of Cardiothoracic Surgery, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York 10025, USA. sbalaram@chpnet.org

BACKGROUND: Abnormal positioning and size of the mitral valve contribute to the systolic anterior motion and mitral-septal contact that are important components of obstructive hypertrophic cardiomyopathy (HCM). The RPR repair (resection of the septum, plication of the anterior leaflet, and release of papillary muscle attachments) addresses all aspects of this complex pathology. This study reports outcomes regarding effectiveness of the RPR repair. METHODS: Fifty consecutive unselected patients (average age, 55.8 years) undergoing RPR repair for obstructive HCM from 1997 to 2007 were studied. Each patient underwent preoperative and postoperative transthoracic echocardiograms to document gradient, ejection fraction, degree of mitral regurgitation, and systolic anterior motion. Intraoperative transesophageal echocardiogram was used to guide all surgical repairs. Clinical follow-up included patient interviews to determine New York Heart Association (NYHA) status. RESULTS: Concomitant operations were performed in 25 patients (50%). Postoperative mortality was 0%. Average mean left ventricular outflow tract gradients decreased from 134 +/- 40 to 2.8 +/- 8.0. Mitral regurgitation improved from a mean of 2.5 to 0.1 (p < 0.001). Average length of stay was 6.9 +/- 2.7 days. NYHA class improved from 3.0 +/- 0.6 to 1.2 +/- 0.5. Follow-up was 100%, with a mean of 2.5 +/- 1.8 years. Average mitral regurgitation at follow-up was 0.9, with no residual systolic anterior motion. CONCLUSIONS: The RPR repair is safe and effective for symptomatic obstructive HCM. Our data support repair of the mitral valve that results in good intermediate outcomes with respect to gradient, mitral regurgitation, and clinical status.

Risks and challenges of implantable cardioverter-defibrillators in young adults.

Sherrid MV, Daubert JP.

Prog Cardiovasc Dis. 2008 Nov-Dec;51(3):237-63.

Cardiology Division, Department of Medicine, St. Luke's-Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, New York City, NY 10019, USA. msherrid@chpnet.org

The clinical use of the implantable cardioverter-defibrillator (ICD) is well established to prevent sudden death in patients with left ventricular dysfunction due to coronary artery disease and dilated cardiomyopathy, and its use has saved thousands of lives. More recently, its use has been extended to other patients at risk for sudden cardiac arrest due to ventricular fibrillation: patients with structural heart diseases such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia and patients with normal cardiac anatomy and function except for electrophysiologic abnormalities that predispose to cardiac arrest: Brugada syndrome and long QT syndrome. A distinguishing feature of these patients may be the young age when they present for either primary or secondary prevention. This contrasts with the "first wave" of adult ICD implantations that were usually performed in elderly or middle aged patients. An important consideration in favor of ICD implantation in young patients with sudden death risk is the long and cumulative period of their risk. Similarly, after implantation, these patients will experience the long-term risks of ICD implantation. This review focuses on the unique challenges presented by device implantation in young patients 16 to 45 years of age who may have 4 to 7 decades of life with their devices. Although devices may prolong life, they come with problems that will pose unique challenges for both patients and their physicians. Moreover, because of the long durations, these problems may accelerate as patients age.

Oral disopyramide for the acute treatment of severe outflow obstruction in hypertrophic cardiomyopathy in the ICU setting.

Sirak TE, Sherrid MV.

Chest. 2008 May;133(5):1243-6.

Division of Cardiology, Department of Medicine, St. Luke's-Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, New York, NY 10019, USA.

When severe COPD and obstructive hypertrophic cardiomyopathy (HCM) coexist, management is challenging and complex. Drug contraindications limit pharmacologic options. Patients may not be candidates for surgical septal myectomy due to severe pulmonary disease. We describe a case of an elderly woman with severe reactive COPD who presented with an infectious exacerbation and dyspnea that progressed to near intubation due to heart failure from coexistent obstructive HCM. Transthoracic echocardiography revealed massive asymmetric septal hypertrophy and a diffusely hyperkinetic left ventricle with a left ventricular outflow tract (LVOT) gradient of 92 mm Hg. Two and a half hours after oral administration of disopyramide, LVOT gradient had decreased to 25 mm Hg with a corresponding immediate improvement in symptoms.

Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy

Barac I, Upadya S, Pilchik R, Winson G, Passick M, Chaudhry FA, Sherrid MV.

J Am Coll Cardiol. 2007 Mar 20;49(11):1203-11. Comment in: J Am Coll Cardiol. 2007 Sep 4;50(10):1006; author reply 1006-7.

Division of Cardiology, St. Luke's-Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, New York, New York 10019, USA.

OBJECTIVES: We investigated the cause of the midsystolic drop (MSD) in left ventricular (LV) ejection velocities that are observed with hypertrophic cardiomyopathy (HCM) and severe obstruction. BACKGROUND: Dynamic obstruction is an important determinant of symptoms and adverse outcome. The MSD in velocity and flow occurs in patients with gradients >60 mm Hg. The nadir velocity in the LV occurs simultaneously with peak gradient. METHODS: We studied 36 patients with obstructive HCM and an MSD and compared them with 15 patients with HCM and no obstruction and with 25 age-matched normal control subjects. We measured LV ejection velocity proximal and distal to LV obstruction as well as tissue Doppler velocities and time intervals. RESULTS: The duration of contraction of both the septum and lateral wall is shorter in obstructed patients with the MSD than in nonobstructed HCM patients: septal contraction 203 +/- 68 ms vs. 271 +/- 41 ms (p < 0.001). Parallel reduction in the length of shortening was noted: 1.2 +/- 0.6 cm vs. 1.9 +/- 0.4 cm (p < 0.001). The ejection velocity nadir follows the septal and lateral peak velocities by 100 ms and 60 ms, respectively. The velocity nadir occurs as both walls rapidly decelerate to their premature termination: septal deceleration 79 +/- 35 cm/s2 vs. 48 +/- 21 cm/s2 (p < 0.001). With medical abolition of obstruction the MSD disappears and the duration and length of contraction normalizes. CONCLUSIONS: These data indicate that the MSD is caused by premature termination of LV segmental shortening and is a manifestation of systolic dysfunction.

Oral disopyramide for the acute treatment of severe outflow obstruction in hypertrophic cardiomyopathy in the ICU setting.

Sirak TE, Sherrid MV.

Chest. 2008 May;133(5):1243-6.

Division of Cardiology, Department of Medicine, St. Luke's-Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, New York, NY 10019, USA.

Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy

Maron BJ, Spirito P, Shen WK, Haas TS, Formisano F, Link MS, Epstein AE, Almquist AK, Daubert JP, Lawrenz T, Boriani G, Estes NA 3rd, Favale S, Piccininno M, Winters SL, Santini M, Betocchi S, Arribas F, Sherrid MV, Buja G, Semsarian C, Bruzzi P.

JAMA. 2007 Jul 25;298(4):405-12.

Hypertrophic Cardiomyopathy Center of the Minneapolis Heart Institute Foundation, Minneapolis, Minnesota 55407, USA. hcm.maron@mhif.org

CONTEXT: Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. OBJECTIVE: To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. DESIGN, SETTING, AND PATIENTS: Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. MAIN OUTCOME MEASURE: Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. RESULTS: The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). CONCLUSIONS: In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

Pathophysiology and treatment of hypertrophic cardiomyopathy.

Sherrid, Mark V.

Progress in Cardiovascular Diseases. 49(2):123-51, 2006 Sep-Oct.

All patients with hypertrophic cardiomyopathy (HCM) should have five aspects of care addressed. An attempt should be made to detect the presence or absence of risk factors for sudden arrhythmic death. If the patient appears to be at high risk, discussion of the benefits and risks of ICD are indicated, and many such patients will be implanted. Symptoms are appraised and treated. Bacterial endocarditis prophylaxis is recommended. Patients are advised to avoid athletic competition and extremes of physical exertion. First degree family members should be screened with echocardiography and ECG.

Comparison of diastolic septal perforator flow velocities in hypertrophic cardiomyopathy versus hypertensive left ventricular hypertrophy.

Sherrid MV. Mahenthiran J. Casteneda V. Fincke R. Gasser M. Barac I. Thayaparan R. Chaudhry FA.

American Journal of Cardiology. 97(1):106-12, 2006 Jan 1.

In this study, we measured diastolic septal perforator flow velocities by Doppler transthoracic echocardiography (TTE) in patients with hypertrophic cardiomyopathy (HCM). Using color-guided pulsed Doppler TTE, septal perforator flow velocity recordings were attempted in 69 patients and successfully recorded in 47 (68%). First, we compared 14 patients with HCM to 12 controls and to 11 patients with hypertension with left ventricular hypertrophy. Next, in 10 additiona patients with HCM, we compared the septal velocities with the epicardial left anterior descending artery (LAD) velocities recorded during the same TTE study. In the patients with HCM, the peak septal diastolic velocities were twice that of the normal controls (88 +/- 40 vs 41 +/- 13 cm/s) and also higher than in hypertensive left ventricular hypertrophy (51 +/- 18 cm/s, p < 0.0001). All 10 patients with HCM showed a step-up of peak diastolic velocity from the LAD to the septal perforator from 41 +/- 9 to 72 +/- 17 cm/s (p < 0.0001). Three patients with HCM had surgical septal myectomy. These patients had luminal narrowings of the small intramural arteries at histopathologic examination. In conclusion, pulsed Doppler measurement of septal perforator flow velocities is feasible. In HCM, the epicardial coronary arteries enlarge to accommodate increased flow, and diastolic velocity is normalized. In contrast, the increased velocities in the septal branches of patients with HCM are similar to those previously observed in tunnel-like obstructions. These findings suggest that in HCM, notwithstanding an increase in coronary flow, hemodynamically significant narrowings are present in the septal branches. Doppler TTE may become useful for evaluation of abnormal intramural coronary flow in HCM.

A Multicenter Study of the Efficacy and Safety of Disopyramide in Obstructive HCM.

Sherrid MV, Barac I, McKenna WJ, Elliott PM, Dickie S, Chojnowska L, Casey S, Maron B.

J American College Cardiology 45; 2005:1251-8.

OBJECTIVES: In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardio myopathy (HCM). BACKGROUND: It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort. METHODES: Clinical and echocardiographic data was evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide. RESULTS: Patients were followed with disopyramide for 3.1 + 2.6 years; dose 432 + 181 mg/ day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 + 33 to 40 + 32 mmHg (p<0.0001) and mean New York Heart Association functional class from 2.3 + 0.7 to 1.7 + 0.6 (p<0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non- disopyramide- treated patients did not differ significantly, 1.4 % versus 2.6 %/year (p=0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p=0.08). CONCLUSION: Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over > 3years. Disopyramide therapy does not appear to be proarrhyhmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.

Beyond Extended Myectomy for HCM: The RPR Operation: Resect-Plicate-Release

Balaram SK , Sherrid MV, DeRose JJ, Hillel Z, Winson G, Swistel DG.

Annals of Thoracic Surgery 80; 2005: 217-23. OBJECTIVES: Extended Myectomy for left ventricular outflow tract obstruction (LVOTO) due to hypertrophic cardiomyopathy (HCM) has good long-tern results. In addition to the mid-septal resection for HCM, our group has introduced a novel variation in anterior leaflet plication (P) to be included with release (R) of papillary muscle attachments. We sought to investigate the medium and long-term success of this three-step repair that addresses all aspects of this complex condition. METHODS: Sixteen patients underwent RPR repair for complex HCM pathology. Transesophageal echocardiography (TEE) was performed on all patients pre-and post-operatively to assess adequacy of resection, left ventricular outflow tract gradients, and mitral valve function. All patients underwent transthoracic outpatient echocardiogram at mean follow-up of 2.4 + 2.1 years ( range 0.5 to 6 years). RESULTS: The average age of the patient was 57 + 14 years. Preoperative LVOTO was 137 + 45 mm Hg. Degree of mitral regurgitation (MR) was 3.1 + 0.8 with all patients exhibiting systolic anterior motion (SAM). Additional concomitant procedures included coronary bypass grafting (n=7), aortic valve replacement (n=2), and radiofrequency atrial fibrillation (n=1). Average length of stay was 7.5 + 3.3 days. No patient was re-hospitalized for heart failure, no patient required reoperation and no patient had died at follow-up. Initial post-operative TEE demonstrated marked reduction in LVOTO to 10 + 17 mm Hg (p<0.0001). At follow-up LVOT gradient remained low at 6 + 14 (p<0.0001) and mitral regurgitation remained mild (0.4 + 0.5) (p<0.0001). CONCLUSIONS: Anterior leaflet plication and papillary muscle release are logical adjuncts to septal resection in the treatment of the complicated pathophysiology of obstructive HCM. Durable long-term results can be achieved with an aggressive approach to mitral valve pathology in conjunction with extended myectomy. Click for Abstract