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138


Thin-filament mutations, hypertrophic cardiomyopathy, and risk [Comment]

Sherrid, Mark V; Arabadjian, Milla; Koulova, Anna
PMID: 25524338
ISSN: 1558-3597
CID: 1570852

Vector flow mapping in obstructive hypertrophic cardiomyopathy to assess the relationship of early systolic left ventricular flow and the mitral valve

Ro, Richard; Halpern, Dan; Sahn, David J; Homel, Peter; Arabadjian, Milla; Lopresto, Charles; Sherrid, Mark V
BACKGROUND: The hydrodynamic cause of systolic anterior motion of the mitral valve (SAM) is unresolved. OBJECTIVES: This study hypothesized that echocardiographic vector flow mapping, a new echocardiographic technique, would provide insights into the cause of early SAM in obstructive hypertrophic cardiomyopathy (HCM). METHODS: We analyzed the spatial relationship of left ventricular (LV) flow and the mitral valve leaflets (MVL) on 3-chamber vector flow mapping frames, and performed mitral valve measurements on 2-dimensional frames in patients with obstructive and nonobstructive HCM and in normal patients. RESULTS: We compared 82 patients (22 obstructive HCM, 23 nonobstructive HCM, and 37 normal) by measuring 164 LV pre- and post-SAM velocity vector flow maps, 82 maximum isovolumic vortices, and 328 2-dimensional frames. We observed color flow and velocity vector flow posterior to the MVL impacting them in the early systolic frames of 95% of obstructive HCM, 22% of nonobstructive HCM, and 11% of normal patients (p < 0.001). In both pre- and post-SAM frames, we measured a high angle of attack >60 degrees of local vector flow onto the posterior surface of the leaflets whether the flow was ejection (59%) or the early systolic isovolumic vortex (41%). Ricochet of vector flow, rebounding off the leaflet into the cul-de-sac, was noted in 82% of the obstructed HCM, 9% of nonobstructive HCM, and none (0%) of the control patients (p < 0.001). Flow velocities in the LV outflow tract on the pre-SAM frame 1 and 2 mm from the tip of the anterior leaflet were low: 39 and 43 cm/s, respectively. CONCLUSIONS: Early systolic flow impacts the posterior surfaces of protruding MVL initiating SAM in obstructive HCM.
PMID: 25440093
ISSN: 1558-3597
CID: 1570762

Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM Cardiac Magnetic Resonance Substudy Analysis [Letter]

Saberi, Sara; Cardim, Nuno; Yamani, Mohamad; Schulz-Menger, Jeanette; Li, Wanying; Florea, Victoria; Sehnert, Amy J; Kwong, Raymond Y; Jerosch-Herold, Michael; Masri, Ahmad; Owens, Anjali; Lakdawala, Neal K; Kramer, Christopher M; Sherrid, Mark; Seidler, Tim; Wang, Andrew; Sedaghat-Hamedani, Farbod; Meder, Benjamin; Havakuk, Ofer; Jacoby, Daniel
PMID: 33190524
ISSN: 1524-4539
CID: 4875082

Three-Dimensional Imaging and Dynamic Modeling of Systolic Anterior Motion of the Mitral Valve

Vainrib, Alan; Massera, Daniele; Sherrid, Mark V; Swistel, Daniel G; Bamira, Daniel; Ibrahim, Homam; Staniloae, Cezar; Williams, Mathew R; Saric, Muhamed
Left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM) is often caused by systolic anterior motion (SAM) of the mitral valve caused by the interplay between increased left ventricular (LV) wall thickness and an abnormal mitral valve anatomy and geometry. Three-dimensional (3D) echocardiographic imaging of the mitral valve has revolutionized the practice of cardiology, paving the way for new methods to see and treat valvular heart disease. Here we present the novel and incremental value of 3D transesophageal echocardiography (TEE) of SAM visualization. This review first provides step-by-step instructions on acquiring and optimizing 3D TEE imaging of SAM. It then describes the unique and novel findings using standard 3D TEE rendering as well as dynamic mitral valve modeling of SAM from 3D data sets, which can provide a more detailed visualization of SAM features. The findings include double-orifice LVOT caused by the residual leaflet, the dolphin smile phenomenon, and delineation of SAM width. Finally, the review discusses the essential role of 3D TEE imaging for preprocedural assessment and intraprocedural guidance of surgical and novel percutaneous treatments of SAM.
PMID: 33059963
ISSN: 1097-6795
CID: 4641632

Indications for Surgery in Obstructive Hypertrophic Cardiomyopathy [Editorial]

Sherrid, Mark V
PMID: 33342223
ISSN: 2047-9980
CID: 4726052

The Mitral Valve in Hypertrophic Cardiomyopathy: Other Side of the Outflow Tract [Editorial]

Sherrid, Mark V; Adams, David H
PMID: 33153585
ISSN: 1558-3597
CID: 4664372

Analysis of three-chamber view conventional and tagged cine MRI in patients with suspected hypertrophic cardiomyopathy

Chitiboi, Teodora; Kanski, Mikael; Tautz, Lennart; Hennemuth, Anja; Halpern, Dan; Sherrid, Mark; Axel, Leon
OBJECTIVES/OBJECTIVE:To investigate the potential value of adding a tagged three-chamber (3Ch) cine to clinical hypertrophic cardiomyopathy (HCM) magnetic resonance imaging (MRI) protocols, including to help distinguish HCM patients with regionally impaired cardiac function. METHODS:Forty-eight HCM patients, five patients with "septal knuckle" (SK), and 20 healthy volunteers underwent MRI at 1.5T; a tagged 3Ch cine was added to the protocol. Regional strain, myocardial wall thickness, and mitral valve leaflet lengths were measured in the 3Ch view. RESULTS:In HCM, we found a reduced tangential strain with decreased diastolic relaxation in both hypertrophied (p = 0.003) and remote segments (p = 0.035). Strain in the basal septum correlated with the length of the coaptation zone + residual leaflet (r = 0.48, p < 0.001). In the basal free wall, patients with SK had faster relaxation compared to HCM patients with septal hypertrophy. DISCUSSION/CONCLUSIONS:The 3Ch tagged MRI sequence provides useful information for the examination of suspected HCM patients, with minimal additional time cost. Local wall function is closely associated with morphological changes of the mitral apparatus measured in the same plane and may provide insights into mechanisms of obstruction. The additional strain information may be helpful when analyzing local myocardial wall motion patterns in the presence of SK.
PMID: 32152793
ISSN: 1352-8661
CID: 4348832

Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy

Ho, Carolyn Y; Mealiffe, Matthew E; Bach, Richard G; Bhattacharya, Mondira; Choudhury, Lubna; Edelberg, Jay M; Hegde, Sheila M; Jacoby, Daniel; Lakdawala, Neal K; Lester, Steven J; Ma, Yanfei; Marian, Ali J; Nagueh, Sherif F; Owens, Anjali; Rader, Florian; Saberi, Sara; Sehnert, Amy J; Sherrid, Mark V; Solomon, Scott D; Wang, Andrew; Wever-Pinzon, Omar; Wong, Timothy C; Heitner, Stephen B
BACKGROUND:Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM. OBJECTIVES/OBJECTIVE:MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM. METHODS:The MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml. Participants were randomized 1:1:1 to mavacamten at a pharmacokinetic-adjusted dose (targeting plasma levels of 200 or 500 ng/ml), or placebo for 16 weeks, followed by an 8-week washout. Initial dose was 5 mg daily with 1 dose titration at week 6. RESULTS:Fifty-nine participants were randomized (19, 21, 19 patients to 200 ng/ml, 500 ng/ml, placebo, respectively). Their mean age was 54 years, and 58% were women. Serious adverse events occurred in 10% of participants on mavacamten and in 21% participants on placebo. Five participants on mavacamten had reversible reduction in LVEF ≤45%. NT-proBNP geometric mean decreased by 53% in the pooled mavacamten group versus 1% in the placebo group, with geometric mean differences of -435 and -6 pg/ml, respectively (p = 0.0005). Cardiac troponin I (cTnI) geometric mean decreased by 34% in the pooled mavacamten group versus a 4% increase in the placebo group, with geometric mean differences of -0.008 and 0.001 ng/ml, respectively (p = 0.009). CONCLUSIONS:Mavacamten, a novel myosin inhibitor, was well tolerated in most subjects with symptomatic nHCM. Furthermore, treatment was associated with a significant reduction in NT-proBNP and cTnI, suggesting improvement in myocardial wall stress. These results set the stage for future studies of mavacamten in this patient population using clinical parameters, including LVEF, to guide dosing. (A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy [MAVERICK-HCM]; NCT03442764).
PMID: 32466879
ISSN: 1558-3597
CID: 4451912

Distinctive Hypertrophic Cardiomyopathy Anatomy and Obstructive Physiology in Patients Admitted With Takotsubo Syndrome

Sherrid, Mark V; Riedy, Katherine; Rosenzweig, Barry; Massera, Daniele; Saric, Muhamed; Swistel, Daniel G; Ahluwalia, Monica; Arabadjian, Milla; DeFonte, Maria; Stepanovic, Alexandra; Serrato, Stephanie; Xia, Yuhe; Zhong, Hua; Maron, Martin S; Maron, Barry J; Reynolds, Harmony R
Clinical spectrum of hypertrophic cardiomyopathy (HC) has been expanded to include patients with mild or no thickening of the left ventricle (LV), who nevertheless have outflow tract obstruction at rest or after exercise, due to systolic anterior motion (SAM) and ventricular septal contact, with mitral valve elongation and papillary muscles anomalies. Apical ballooning mimicking a takotsubo syndrome (TS) wall motion pattern can occur in HC with mild septal thickening when latent obstruction becomes unrelenting. To define the prevalence of anatomic abnormalities characteristic of HC in patients diagnosed with TS, we analyzed echocardiograms of 44 unselected TS patients, age 67±12 years, 95% women including studies performed before the event (n = 11, median 515 days) and after recovery of left ventricular function (n = 33, median 92 days, interquartile range = 29 to 327) and compared the findings to 60 age and sexed matched controls. Analysis of echocardiograms was blinded to event timing, and patient vs. control status. During the ballooning event, 13 patients (30%) had SAM including 9 with LV outflow obstruction, peak gradients 71±40 mmHg, as well as: ventricular septal thickening (16 ± 4 mm), elongated anterior leaflets (30 ± 3mm), and increased mitral coaptation to posterior wall distance (17 ± 5 mm), consistent with diagnosis of the HC phenotype. Compared to 31 TS patients without SAM, study patients with SAM had longer anterior leaflets (30 ± 3 vs 26 ± 4 mm, p = 0.006), thicker septum (16 ± 4 vs 12 ± 3 mm), increased coaptation to posterior wall distance (17 ± 5 vs 14 ± 4 mm, p < 0.04) and reduced distance from coaptation to septum (19 ± 5 vs 27 ± 5, p < 0.001). In the 13 patients with SAM, morphologic characteristics of HC persisted after normalization of LV function. In conclusion, a subset of patients experiencing TS events demonstrates a constellation of morphologic abnormalities characteristic of HC that persist after recovery of LV wall motion. These findings suggest that dynamic outflow obstruction may cause apical ballooning in susceptible patients.
PMID: 32278461
ISSN: 1879-1913
CID: 4383042

On-pump intracardiac echocardiography during septal myectomy for hypertrophic cardiomyopathy

Williams, David M; Nampi, Robert G; Saric, Muhamed; Grossi, Eugene A; Sherrid, Mark V; Swistel, Daniel G
PMCID:8298854
PMID: 34317753
ISSN: 2666-2507
CID: 4949552