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Medical, Surgical, and Interventional Management of Hypertrophic Cardiomyopathy
Massera, Daniele; Sherrid, Mark V; Scheinerman, Joshua A; Swistel, Daniel G; Razzouk, Louai
Hypertrophic cardiomyopathy is a common but underrecognized cardiac disorder characterized by a heterogenous phenotype that includes increased left ventricular thickness, outflow obstruction, diastolic dysfunction, and arrhythmia. Hypertrophic cardiomyopathy is often heritable and associated with pathogenic variants in sarcomeric genes. While not curable, an integrated approach involving medical, interventional, and surgical care can have a considerable impact on disease burden, quality of life, and mortality. This review provides a practical overview of important topics in hypertrophic cardiomyopathy, including evaluation of differential diagnosis, imaging, provocation of left ventricular outflow obstruction, treatment of obstructive and nonobstructive hypertrophic cardiomyopathy with negative inotropic therapy and myosin inhibition, as well as surgical and interventional approaches to septal reduction and mitral valve intervention.
PMID: 39925290
ISSN: 1941-7632
CID: 5793102
Integrating Quality Metrics with Enhanced Recovery Pathways in Coronary Artery Bypass Grafting
Phillips, Katherine G; Galloway, Aubrey; Grossi, Eugene A; Swistel, Daniel; Smith, Deane E; Mosca, Ralph; Zias, Elias
Perspective Statement: Beyond the Society of Thoracic Surgery's (STS) quality metrics, many other operative measures, such as completeness of revascularization, and patient care measures add quality and value for patients undergoing coronary artery bypass surgery; and Enhanced Recovery after Surgery (ERAS) protocols have improved patient experience and recovery, leading to better outcomes and significant healthcare savings.
PMID: 39892624
ISSN: 1532-9488
CID: 5781422
Midterm survival, clinical, and hemodynamic outcomes of a novel mechanical mitral valve prosthesis
Ruel, Marc; Chu, Michael W A; Graeve, Allen; Gerdisch, Marc W; Damiano, Ralph J; Smith, Robert L; Keeling, William Brent; Wait, Michael A; Hagberg, Robert C; Quinn, Reed D; Sethi, Gulshan K; Floridia, Rosario; Barreiro, Christopher J; Pruitt, Andrew L; Accola, Kevin D; Dagenais, Francois; Markowitz, Alan H; Ye, Jian; Sekela, Michael E; Tsuda, Ryan Y; Duncan, David A; Swistel, Daniel G; Harville, Lacy E; DeRose, Joseph J; Lehr, Eric J; Alexander, John H; Puskas, John D; ,
OBJECTIVE:To evaluate the midterm survival, clinical, and hemodynamic outcomes of the On-X mechanical mitral valve, based on the 5-year results of the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT). METHOD/METHODS:PROACT Mitral was a multicenter study evaluating 401 patients who underwent mitral valve replacement (MVR) with either Standard or Conform-X On-X mitral valves, comparing low-dose and standard-dose warfarin. Here we report prespecified secondary outcomes of survival, New York Heart Association (NYHA) functional classification, and valve hemodynamics as assessed by core lab-adjudicated echocardiography at 1, 3, and 5 years in the pooled population. RESULTS:Actuarial survival was 99.7% at 1 year, 95.1% at 3 years, and 92.4% at 5 years, with no significant difference between the Standard and Conform-X cuffs. Hemodynamic analysis revealed a mean transvalvular pressure gradient (MG) of 4.6 ± 2.0 mm Hg at 1 year, with no interaction between valve size and patient body surface area. MG values were consistent over time. Quality of life improved with 96.6% of patients in NYHA class I or II at the latest available follow-up of 3 or 5 years. There were no significant differences in survival, clinical, or hemodynamic outcomes between valve sizes. CONCLUSIONS:The On-X mechanical mitral valve demonstrated favorable survival, stable hemodynamics, and enhanced quality of life up to 5 years postimplantation. Derived from high-quality, rigorous randomized trial data, these findings can guide decision making in young patients requiring MVR.
PMID: 39617318
ISSN: 1097-685x
CID: 5781722
Comprehensive Proteomic Profiling of Human Myocardium Reveals Signaling Pathways Dysregulated in Hypertrophic Cardiomyopathy
Lumish, Heidi S; Sherrid, Mark V; Janssen, Paul M L; Ferrari, Giovanni; Hasegawa, Kohei; Castillero, Estibaliz; Adlestein, Elizabeth; Swistel, Daniel G; Topkara, Veli K; Maurer, Mathew S; Reilly, Muredach P; Shimada, Yuichi J
BACKGROUND:Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Signaling pathways that link genetic sequence variants to clinically overt HCM and progression to severe forms of HCM remain unknown. OBJECTIVES/OBJECTIVE:The purpose of this study was to identify signaling pathways that are differentially regulated in HCM, using proteomic profiling of human myocardium, confirmed with transcriptomic profiling. METHODS:In this multicenter case-control study, myocardial samples were obtained from cases with HCM and control subjects with nonfailing hearts. Proteomic profiling of 7,289 proteins from myocardial samples was performed using the SomaScan assay (SomaLogic). Pathway analysis of differentially expressed proteins was performed, using a false discovery rate <0.05. Pathway analysis of proteins whose concentrations correlated with clinical indicators of severe HCM (eg, reduced left ventricular ejection fraction, atrial fibrillation, and ventricular tachyarrhythmias) was also executed. Confirmatory analysis of differentially expressed genes was performed using myocardial transcriptomic profiling. RESULTS:The study included 99 HCM cases and 15 control subjects. Pathway analysis of differentially expressed proteins revealed dysregulation of the Ras-mitogen-activated protein kinase, ubiquitin-mediated proteolysis, angiogenesis-related (eg, hypoxia-inducible factor-1, vascular endothelial growth factor), and Hippo pathways. Pathways known to be dysregulated in HCM, including metabolic, inflammatory, and extracellular matrix pathways, were also dysregulated. Pathway analysis of proteins associated with clinical indicators of severe HCM and of differentially expressed genes supported these findings. CONCLUSIONS:The present study represents the most comprehensive (>7,000 proteins) and largest-scale (n = 99 HCM cases) proteomic profiling of human HCM myocardium to date. Proteomic profiling and confirmatory transcriptomic profiling elucidate dysregulation of both newly recognized (eg, Ras-mitogen-activated protein kinase) and known pathways associated with pathogenesis and progression to severe forms of HCM.
PMID: 39365226
ISSN: 1558-3597
CID: 5763842
Clinical Course and Treatment of Patients With Apical Aneurysms Due to Hypertrophic Cardiomyopathy
Sherrid, Mark V; Massera, Daniele; Bernard, Samuel; Tripathi, Nidhi; Patel, Yash; Modi, Vivek; Axel, Leon; Talebi, Soheila; Saric, Muhamed; Adlestein, Elizabeth; Alvarez, Isabel Castro; Reuter, Maria C; Wu, Woon Y; Xia, Yuhe; Ghoshhajra, Brian B; Sanborn, Danita Y; Fifer, Michael A; Swistel, Daniel G; Kim, Bette
BACKGROUND/UNASSIGNED:There is controversy about risk of malignant arrhythmias and stroke in patients with apical aneurysms in hypertrophic cardiomyopathy (HCM). OBJECTIVES/UNASSIGNED:The aim of this study was to estimate the associations of aneurysm size and major HCM risk factors with the incidence of lethal and potentially lethal arrhythmias and to estimate incidence of unexplained stroke. METHODS/UNASSIGNED:In 108 patients (age 57.4 ± 13.5 years, 37% female) from 3 HCM centers, we assessed American Heart Association/American College of Cardiology guidelines risk factors and initial aneurysm size by echocardiography and cardiac magnetic resonance imaging and assessed outcomes after median 5.9 (IQR: 3.7-10.0) years. RESULTS/UNASSIGNED:and also without risk factors VT, VF, or SCD occurred in only 2.5%. Clinical atrial fibrillation (AF) was prevalent, occurring in 49 (45%). Stroke was commonly associated with AF. Stroke without conventional cause had an incidence of 0.5%/year. Surgery in 19% was effective in reducing symptoms. VT ablation and surgery were moderately effective in preventing recurrent VT. CONCLUSIONS/UNASSIGNED:Risk factors and aneurysm size were associated with subsequent VT, VF, or SCD. Patients with aneurysms in the lowest tercile of size have a low cumulative 5-year risk. Clinical AF occurred frequently. Stroke prevalence in absence of known stroke etiologies is uncommon and comparable to risk of severe bleeding.
PMCID:11400613
PMID: 39280799
ISSN: 2772-963x
CID: 5719702
Mitral Leaflet Shortening as an Ancillary Procedure in Obstructive Hypertrophic Cardiomyopathy
Swistel, Daniel G; Massera, Daniele; Stepanovic, Alexandra; Adlestein, Elizabeth; Reuter, Maria; Wu, Woon; Scheinerman, Joshua A; Nampi, Robert; Paone, Darien; Kim, Bette; Sherrid, Mark V
BACKGROUND:Mitral leaflet elongation is common in hypertrophic cardiomyopathy (HCM), contributes to obstructive physiology, and presents a challenge to dual surgical goals of abolition of outflow gradients and mitral regurgitation. Anterior leaflet shortening, performed as an ancillary surgical procedure during myectomy, is controversial. METHODS:This was a retrospective study of all patients undergoing myectomy from 1/2010 to 3/2020 analyzing survival and echocardiographic results. We compared outcomes of patients treated with myectomy and concomitant mitral leaflet shortening with patients treated with myectomy alone. Over this time technique for mitral shortening evolved from anterior leaflet plication to residual leaflet excision (ReLex). RESULTS:Myectomy was performed on 416 patients age 57.5±13.6 years, 204 (49%) female. Average follow up was 5.4±2.8 years. Survival follow-up was complete in 415. Myectomy without valve replacement was performed in 332 patients, of whom 192 had mitral valve shortening (58%). Mitral leaflet plication was performed in 73, ReLex in 151 and both in 32. Hospital mortality for patients undergoing myectomy was 0.7%. At 8 years, cumulative survival was 95% for both myectomy plus leaflet shortening and myectomy alone groups, with no difference in survival between the two. There was no difference in survival between anterior leaflet plication and ReLex groups. Echocardiography 2.5 years after surgery showed a decrease in resting and provoked gradients, mitral regurgitation and left atrial volume and no difference in key variables between ancillary leaflet shortening and myectomy alone patients. CONCLUSIONS:These results affirm that mitral shortening may be an appropriate surgical judgment for selected patients.
PMID: 38518836
ISSN: 1552-6259
CID: 5640912
Routine Extubation in the Operating Room After Isolated Coronary Artery Bypass
James, Les; Smith, Deane E; Galloway, Aubrey C; Paone, Darien; Allison, Michael; Shrivastava, Shashwat; Vaynblat, Mikhail; Swistel, Daniel G; Loulmet, Didier F; Grossi, Eugene A; Williams, Mathew R; Zias, Elias
BACKGROUND:The benefits of fast-track extubation in the intensive care unit (ICU) after cardiac surgery are well established. Although extubation in the operating room (OR) is safe in carefully selected patients, widespread use of this strategy in cardiac surgery remains unproven. This study was designed to evaluate perioperative outcomes with OR vs ICU extubation in patients undergoing nonemergency, isolated coronary artery bypass grafting (CABG). METHODS:The Society of Thoracic Surgeons (STS) data for all single-center patients who underwent nonemergency isolated CABG over a 6-year interval were analyzed. Perioperative morbidity and mortality with ICU vs OR extubation were compared. RESULTS:Between January 1, 2017 and December 31, 2022, 1397 patients underwent nonemergency, isolated CABG; 891 (63.8%) of these patients were extubated in the ICU, and 506 (36.2%) were extubated in the OR. Propensity matching resulted in 414 pairs. In the propensity-matched cohort, there were no differences between the 2 groups in incidence of reintubation, reoperation for bleeding, total operative time, stroke or transient ischemic attack, renal failure, or 30-day mortality. OR-extubated patients had shorter ICU hours (14 hours vs 20 hours; P < .0001), shorter postoperative hospital length of stay (3 days vs 5 days; P < .0001), a greater likelihood of being discharged directly to home (97.3% vs 89.9%; P < .0001), and a lower 30-day readmission rate (1.7% vs 4.1%; P = .04). CONCLUSIONS:Routine extubation in the OR is a feasible and safe strategy for a broad spectrum of patients after nonemergency CABG, with no increase in perioperative morbidity or mortality. Wider adoption of routine OR extubation for nonemergency CABG is indicated.
PMID: 37806334
ISSN: 1552-6259
CID: 5605312
Apical Aneurysms and Mid-Left Ventricular Obstruction in Hypertrophic Cardiomyopathy
Sherrid, Mark V; Bernard, Samuel; Tripathi, Nidhi; Patel, Yash; Modi, Vivek; Axel, Leon; Talebi, Soheila; Ghoshhajra, Brian B; Sanborn, Danita Y; Saric, Muhamed; Adlestein, Elizabeth; Alvarez, Isabel Castro; Xia, Yuhe; Swistel, Daniel G; Massera, Daniele; Fifer, Michael A; Kim, Bette
BACKGROUND:Apical left ventricular (LV) aneurysms in hypertrophic cardiomyopathy (HCM) are associated with adverse outcomes. The reported frequency of mid-LV obstruction has varied from 36% to 90%. OBJECTIVES/OBJECTIVE:The authors sought to ascertain the frequency of mid-LV obstruction in HCM apical aneurysms. METHODS:The authors analyzed echocardiographic and cardiac magnetic resonance examinations of patients with aneurysms from 3 dedicated programs and compared them with 63 normal controls and 47 controls with apical-mid HCM who did not have aneurysms (22 with increased LV systolic velocities). RESULTS:]; P = 0.004). Complete emptying occurs circumferentially around central PMs that contribute to obstruction. Late gadolinium enhancement was always brightest and the most transmural apical of, or at the level of, complete emptying. CONCLUSIONS:The great majority (95%) of patients in the continuum of apical aneurysms have associated mid-LV obstruction. Further research to investigate obstruction as a contributing cause to apical aneurysms is warranted.
PMID: 36681586
ISSN: 1876-7591
CID: 5419392
Histopathology of the Mitral Valve Residual Leaflet in Obstructive Hypertrophic Cardiomyopathy
Troy, Aaron L; Narula, Navneet; Massera, Daniele; Adlestein, Elizabeth; Alvarez, Isabel Castro; Janssen, Paul M L; Moreira, Andre L; Olivotto, Iacopo; Stepanovic, Alexandra; Thomas, Kristen; Zeck, Briana; Chiriboga, Luis; Swistel, Daniel G; Sherrid, Mark V
BACKGROUND:Mitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown. OBJECTIVES/OBJECTIVE:The purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the valve. METHODS:Structural and immunohistochemical staining were performed on 22 residual leaflets excised as ancillary procedures during myectomy, and compared with 11 control leaflets from deceased patients with normal hearts. Structural components were assessed with hematoxylin and eosin, trichrome, and elastic stains. We stained for EPDCs, EPDC paracrine signaling, valvular interstitial cells, endocardial-to-mesenchymal transition, and cardiomyocytes. RESULTS:= 0.08). No markers of primary cellular processes were identified. CONCLUSIONS:MV residual leaflets in HCM were characterized by histologic findings that were likely secondary to chronic hemodynamic stress and may further increase susceptibility to systolic anterior motion.
PMCID:10306242
PMID: 37383048
ISSN: 2772-963x
CID: 5540432
Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial
Chu, Michael W A; Ruel, Marc; Graeve, Allen; Gerdisch, Marc W; Damiano, Ralph J; Smith, Robert L; Keeling, William Brent; Wait, Michael A; Hagberg, Robert C; Quinn, Reed D; Sethi, Gulshan K; Floridia, Rosario; Barreiro, Christopher J; Pruitt, Andrew L; Accola, Kevin D; Dagenais, Francois; Markowitz, Alan H; Ye, Jian; Sekela, Michael E; Tsuda, Ryan Y; Duncan, David A; Swistel, Daniel G; Harville, Lacy E; DeRose, Joseph J; Lehr, Eric J; Alexander, John H; Puskas, John D
BACKGROUND:Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS:After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS:Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, -0.07%; 95% CI, -3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS:Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).
PMID: 36610532
ISSN: 1552-6259
CID: 5426292