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1.
Circulation ; 144(6): 426-437, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34039025

RESUMO

BACKGROUND: In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone. METHODS: Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days. RESULTS: TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [P<0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [P<0.0001]). This relationship was consistent in the TMVr and GDMT arms (Pinteraction=0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (-0.3±1.7 versus -9.4±4.6 [P=0.0008]) consistently in both groups (Pinteraction=0.95). CONCLUSIONS: In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência da Valva Mitral/epidemiologia , Qualidade de Vida , Cateterismo Cardíaco , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Próteses Valvulares Cardíacas , Humanos , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/terapia , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Vigilância em Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fatores de Tempo
2.
J Immunol ; 205(10): 2806-2820, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33055281

RESUMO

Intermediate monocytes (iMo; CD14+CD16+) increase in number in the circulation of patients with unstable coronary artery disease (CAD), and their recruitment to inflamed arteries is implicated in events leading to mortality following MI. Monocyte recruitment to inflamed coronary arteries is initiated by high affinity ß2-integrin (CD11c/CD18) that activates ß1-integrin (VLA-4) to bind endothelial VCAM-1. How integrin binding under shear stress mechanosignals a functional shift in iMo toward an inflammatory phenotype associated with CAD progression is unknown. Whole blood samples from patients treated for symptomatic CAD including non-ST elevation MI, along with healthy age-matched subjects, were collected to assess chemokine and integrin receptor levels on monocytes. Recruitment on inflamed human aortic endothelium or rVCAM-1 under fluid shear stress was assessed using a microfluidic-based artery on a chip (A-Chip). Membrane upregulation of high affinity CD11c correlated with concomitant activation of VLA-4 within focal adhesive contacts was required for arrest and diapedesis across inflamed arterial endothelium to a greater extent in non-ST elevation MI compared with stable CAD patients. The subsequent conversion of CD11c from a high to low affinity state under fluid shear activated phospho-Syk- and ADAM17-mediated proteolytic cleavage of CD16. This marked the conversion of iMo to an inflammatory phenotype associated with nuclear translocation of NF-κB and production of IL-1ß+ We conclude that CD11c functions as a mechanoregulator that activates an inflammatory state preferentially in a majority of iMo from cardiac patients but not healthy patients.


Assuntos
Antígeno CD11c/metabolismo , Doença da Artéria Coronariana/imunologia , Endotélio Vascular/imunologia , Monócitos/imunologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/imunologia , Adulto , Idoso , Regulação Alostérica/imunologia , Aorta/citologia , Estudos de Casos e Controles , Técnicas de Cultura de Células , Linhagem Celular , Membrana Celular/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/citologia , Vasos Coronários/imunologia , Células Endoteliais/citologia , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Feminino , Humanos , Integrina alfa4beta1/metabolismo , Dispositivos Lab-On-A-Chip , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Migração Transendotelial e Transepitelial/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
3.
Catheter Cardiovasc Interv ; 98(5): 1000-1005, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002282

RESUMO

Endomyocardial biopsy (EMB) is a common procedure used to aid in the diagnosis of diffuse myocardial diseases and, less commonly, in the diagnosis of cardiac tumors. As cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount, and additional imaging, like transesophageal echocardiography is often required for guidance. The use of intracardiac echocardiography (ICE) to guide biopsy has been described, but there is no consensus on a standardized approach. We report our institutional approach with three cases of ICE-directed EMB performed with the 2.4 mm Jawz bioptome directed with an 8.5-Fr Agilis NxT steerable introducer. All cases were performed under guidance with the AcuNav ICE probe. There were no procedural complications and a definitive diagnosis was obtained in all three cases. We also review the available published cases of ICE-guided EMB in the literature-noting the different procedural approaches, complication rate, and diagnostic yield. There were only two negative biopsies reported among the published cases and no reported complications. Our review of all these cases suggests that ICE-guidance for EMB is superior to other forms of imaging in its ease of use and high definition of right-sided cardiac structures. We also feel that the use of the Agilis steerable sheath allows for more precise directing of the bioptome and is a critical component in performing a successful targeted biopsy.


Assuntos
Cardiomiopatias , Ventrículos do Coração , Biópsia , Cateterismo Cardíaco , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Resultado do Tratamento
4.
Catheter Cardiovasc Interv ; 97(4): 745-754, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33045138

RESUMO

BACKGROUND: During MitraClip implantation sub-valvular correction of trajectory and/or alignment may increase adverse clip or leaflet events. With systematic adjunctive use of fluoroscopy ("Parallax technique"), we aimed to assess parameters that minimize the need for corrective measures and help increase procedural efficiency. METHODS: We retrospectively analyzed 30 patients without (Fl-) and 39 patients utilizing adjunctive fluoroscopy (Fl+) during MitraClip implantation. After establishing trajectory and supra-valvular alignment, the Parallax technique was utilized. Trajectory and alignment are maintained during advancement. RESULTS: All patients had 3 or 4+ MR. There were no differences in baseline demographics. The average number of clips (Fl- vs Fl+) was 1.72 ± 0.8 vs 1.59 ± 0.5, p = .57. For the first clip, the need for sub-valvular alignment (80% vs. 36%, p = .0001), eversion with retraction back to left atrium (23% vs. 10%, p = .001) and the number of grasps (2.3 ± 1.2 vs 1.4 ± 0.9) was reduced. The time from transseptal puncture to first clip deployment (71 ± 21 vs 44 ± 16 min, p = .01) was reduced. Procedural success was achieved in all but one patient in the Fl- group (p = ns). There were no differences noted for in-hospital or 30-day outcomes. CONCLUSIONS: Systematic use of a simple and easy to implement "Parallax technique" was associated with reduced need for sub-valvular manipulation and was associated with improved procedural times. Further larger scale studies are needed to assess the applicability of the technique.


Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Fluoroscopia , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Catheter Cardiovasc Interv ; 96(1): 210-214, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31617308

RESUMO

MitraClip is used for reduction of mitral insufficiency in patients who are not good surgical candidates, but with expanding indications, the use of MitraClip and the number of complications will increase. Here is presented a case of a single leaflet device attachment that worsened the patient's mitral insufficiency, as well as the technique for stabilizing the valve followed by retrieval of the device. A special focus is placed on removing the using a two-snare technique to avoid the need for a surgical cutdown and repair.


Assuntos
Cateterismo Cardíaco , Remoção de Dispositivo , Migração de Corpo Estranho/terapia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Idoso , Feminino , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/etiologia , Átrios do Coração/diagnóstico por imagem , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Resultado do Tratamento
6.
Catheter Cardiovasc Interv ; 96(3): 699-705, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259371

RESUMO

The MitraClip procedure is carried out almost exclusively via the transfemoral approach. However, in some patients transfemoral delivery of MitraClip is not technically feasible (e.g., occluded inferior vena cava or tortuous/obstructive iliofemoral venous anatomy). The technical considerations and challenges of the MitraClip procedure are amplified when an alternate route is considered. We describe a successful case of MitraClip performed via the right internal jugular (IJ) approach in a patient with a flail A3 scallop and previous mitral valve repair. We reviewed prior cases in the literature and discuss step-by-step the pertinent clinical and technical considerations for performing this procedure via the transjugular route. In summary, the right IJ access site provides a reasonable alternative to perform the MitraClip procedure in cases where femoral access is contraindicated or prohibitive. A thorough understanding of the technical considerations is crucial in improving procedural success rates.


Assuntos
Cateterismo Cardíaco/instrumentação , Cateterismo Venoso Central , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Veias Jugulares , Anuloplastia da Valva Mitral/instrumentação , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Humanos , Veias Jugulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Recuperação de Função Fisiológica , Reoperação , Resultado do Tratamento
7.
Catheter Cardiovasc Interv ; 96(3): E387-E392, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32077578

RESUMO

OBJECTIVES: To propose a novel method for mapping leak location and frequency to a clock-face representation of the left atrial appendage (LAA) ostium. BACKGROUND: LAA occlusion with the Watchman device (WD) is an established therapy to reduce thromboembolic events in patients with atrial fibrillation (AF) and intolerance to long-term oral anticoagulation. Postimplantation leaks are known sequelae, but leak locations and characteristics are poorly described. METHODS: We retrospectively reviewed 101 consecutive WD implants from April 2015 to February 2018. Leak locations from 6-week post-implant transesophageal echocardiograms were mapped to a clock-face representation of the LAA ostium: 12:00 as cranial near the limbus, 3:00 as anterior toward the pulmonary artery, 6:00 as caudal near the mitral annulus, and 9:00 as posterior. Patient demographics, LAA dimensions, and procedural characteristics were also collected. RESULTS: Thirty-four patients had ≥1 leak totaling 45 leaks at 6-week follow-up. Baseline patient demographics showed a mean age 77, CHA2 DS2 VASc 4.69, and 64% of patients with permanent AF. No patient had a detectable leak at the time of implant. At 6 weeks, mean leak size was 2.67 ± 0.89 mm with no leak over 5 mm (largest 4.60 mm). Most leaks occurred along the posterior 6:00-12:00 segment (39/45) and the 6:00-9:00 quadrant (16/45). CONCLUSION: Six-week post-WD implant leaks localize to the posterior LAA ostium. This could result from the elliptical LAA orifice, differential LAA tissue composition, or implantation technique. This study provides a novel method for describing the location of post-implant leaks and serves as the basis for further investigations.


Assuntos
Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Ecocardiografia Transesofagiana , Falha de Prótese , Dispositivo para Oclusão Septal , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Catheter Cardiovasc Interv ; 95(3): 414-419, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31638326

RESUMO

A transseptal puncture is critical for "left-sided" structural heart interventions. Procedures such as transcatheter edge-to-edge repair (MitraClip) and left atrial appendage (LAA) closure (Watchman) require precise puncture of the interatrial septum (IAS), and the presence of a prior atrial septal defect (ASD) closure device poses a challenge. We aim to present a successfully completed case of MitraClip and Watchman in the presence of ASD closure device in two different patients. A review of the literature will be reported, and pertinent clinical and technical considerations will be discussed in depth to achieve procedural success. In summary, transseptal puncture for left heart structural interventions is feasible in the presence of a prior ASD/patent foramen ovale closure device. A detailed understanding of the anatomical considerations as well as the use of multimodality imaging to evaluate the IAS will aid in improving procedural success rates.


Assuntos
Fibrilação Atrial/terapia , Cateterismo Cardíaco , Comunicação Interatrial/terapia , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Cateterismo Cardíaco/instrumentação , Feminino , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/fisiopatologia , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Hemodinâmica , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Punções , Recuperação de Função Fisiológica , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Catheter Cardiovasc Interv ; 94(6): 829-836, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31001927

RESUMO

OBJECTIVES: Review indications and outcomes for transcatheter iatrogenic atrial septal defect (iASD) closure in patients undergoing MitraClip or transseptal (TS) mitral valve-in-valve/ring (ViV/ViR) procedures. BACKGROUND: Mitral valve transcatheter interventions require large-diameter TS sheaths that can result in iASDs that necessitate post-procedure transcatheter closure. Although the presence of iASD has been well-described, indications for closure and outcomes after TS mitral valve interventions have not been reported. METHODS: Patients undergoing MitraClip repair and ViV or ViR transcatheter mitral valve replacement (TMVR) from February 14, 2014, to January 16, 2018, were studied retrospectively in this single center study. RESULTS: Seventeen patients had iASD closure: 11 MitraClip and 6 TMVR (5 ViV, 1 ViR). Indications for iASD closure included large iASD (n = 7), large left-to-right shunt (n = 9), pulmonary hypertension (n = 8), large right-to-left shunt (n = 1), severe RV dysfunction (n = 2), thin/aneurysmal septum (n = 2), and mobile material on pacemaker leads (n = 2). Closures were performed without complications using Amplatzer septal occluders. At 30 days, 94% of subjects (n = 16) were alive with one patient deceased from unknown causes. There were no myocardial infarctions or strokes. At 12 months, follow-up was available for 14 of 17 patients, and 71% of patients (10/14) were alive. One patient died due to cardiac causes, two from noncardiac causes and one for unknown reasons. There was one myocardial infarction, one intraparenchymal hemorrhage, and no ischemic strokes. CONCLUSIONS: The most common reasons for iASD closure after TS MV procedures are: large ASD unlikely to spontaneously close, large left-to-right shunt, and pulmonary hypertension. Patients who required iASD closure had low 30-day mortality but higher one-year mortality potentially reflecting a population with substantial comorbidities.


Assuntos
Septo Interatrial/lesões , Cateterismo Cardíaco/efeitos adversos , Traumatismos Cardíacos/terapia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valva Mitral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Septo Interatrial/diagnóstico por imagem , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/mortalidade , Cateteres Cardíacos , Feminino , Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/mortalidade , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Doença Iatrogênica , Masculino , Valva Mitral/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Dispositivo para Oclusão Septal , Fatores de Tempo , Resultado do Tratamento
10.
Catheter Cardiovasc Interv ; 93(5): E311-E317, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30311343

RESUMO

OBJECTIVES: To compare left atrial appendage (LAA) angiography to transesophageal echocardiography (TEE) for assessing usable LAA depth. BACKGROUND: TEE is typically employed for procedural measurement of LAA ostial diameter and depth. Since angiography enhances distal LAA anatomy, we sought to compare angiography to TEE for determining usable LAA depth. METHODS: Seventy five Watchman device cases were retrospectively evaluated. Two independent cardiologists measured intraoperative LAA ostial diameter and depth at standard 0°, 45°, 90°, and 135° TEE omniplane views and in the right anterior oblique (RAO) 30°, caudal (CAUD) 30° angiographic view. RESULTS: The average age and CHA2 DS2 VASc score were 74 (±7.2) years and 4.6 (±1.3), respectively. The average ostial diameter and depth (mm) by TEE were 0°: 19.6 and 26.5; 45°: 17.5 and 26.6; 90°: 18.3 and 25.1; 135°: 19.5 and 23.3. The ostial diameter and depth (mm) by RAO 30° CAUD 30° angiography were 21.1 and 29.7. This angiographic view corresponds to a TEE view between 90° and 135°. In comparison to angiography, TEE 90° underestimated the LAA ostial diameter by 2.9 ± 3.7 mm (P < 0.001) and by 1.9 ± 4.0 mm at TEE 135° (P < 0.01); Pearson's r 0.53 angiography/TEE 90° and 0.50 angiography/TEE 135°. More importantly, TEE 90° underestimated the true usable LAA depth by 5.4 ± 5.8 mm (P < 0.001) and by 7.3 ± 6.1 mm at TEE 135° (P < 0.001); Pearson's r 0.39 angiography/TEE 90° and 0.30 angiography/TEE 135°. CONCLUSIONS: Compared to TEE, LAA angiography provides additional depth information and may be particularly valuable when patients have insufficient depth for Watchman by TEE measures.


Assuntos
Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Cateterismo Cardíaco/instrumentação , Angiografia Coronária , Ecocardiografia Transesofagiana , Idoso , Idoso de 80 Anos ou mais , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo , Cateterismo Cardíaco/efeitos adversos , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
11.
Catheter Cardiovasc Interv ; 94(1): 165-170, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30588751

RESUMO

OBJECTIVES: This study investigates the correlation of occlusive wedge pressure (WP) with direct left atrial (LA) pressure in patients with severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVr) with MitraClip. BACKGROUND: There is interest in acquiring objective hemodynamic parameters for intraprocedural guidance in patients undergoing MitraClip. METHODS: The study included 94 patients with severe MR at prohibitive surgical risk who underwent MitraClip at the University of California Davis Medical Center between 2014 and 2016. RESULTS: An average of 1.8 ± 0.7 clips were used to achieve MR grade of 2+ or less in 99% of patients. Correlation analysis of all (n = 236) pre-clip, inter-clip, and final-clip WP and LA pressures yielded a Pearson's R (r) of 0.85 and 0.79 for mean WP vs mean LA and WP V vs LA V, respectively. Median LA V to mean LA ratio (LAV:mLA) was 1.75 (IQR 1.5-1.9). 79% (n = 74) of patients had LAV:mLA ratio ≥ 1.5 with associated WP V vs LA V correlation (r) of 0.83. In patients with LAV:mLA ratio < 1.5, the correlation (r) was 0.69. Baseline characteristics were not significantly different between patients with LAV:mLA ratio ≥ 1.5 and patients with LAV:mLA ratio < 1.5. Post-procedure, median LA V: mean LA ratio decreased from 1.75 to 1.4, P = 0.0001. CONCLUSIONS: Correlation between WP and direct LA pressure in patients with severe MR undergoing Mitraclip is modest. Caution is advised when using WP to approximate LA pressure intraprocedurally, especially in patients with baseline low LAV:mLA ratios.


Assuntos
Função do Átrio Esquerdo , Pressão Atrial , Cateterismo Cardíaco , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Monitorização Intraoperatória , Pressão Propulsora Pulmonar , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Desenho de Prótese , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
12.
Blood ; 128(7): 971-81, 2016 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27335278

RESUMO

Mutations in DNA methyltransferase 3A (DNMT3A) are common in acute myeloid leukemia and portend a poor prognosis; thus, new therapeutic strategies are needed. The likely mechanism by which DNMT3A loss contributes to leukemogenesis is altered DNA methylation and the attendant gene expression changes; however, our current understanding is incomplete. We observed that murine hematopoietic stem cells (HSCs) in which Dnmt3a had been conditionally deleted markedly overexpress the histone 3 lysine 79 (H3K79) methyltransferase, Dot1l. We demonstrate that Dnmt3a(-/-) HSCs have increased H3K79 methylation relative to wild-type (WT) HSCs, with the greatest increases noted at DNA methylation canyons, which are regions highly enriched for genes dysregulated in leukemia and prone to DNA methylation loss with Dnmt3a deletion. These findings led us to explore DOT1L as a therapeutic target for the treatment of DNMT3A-mutant AML. We show that pharmacologic inhibition of DOT1L resulted in decreased expression of oncogenic canyon-associated genes and led to dose- and time-dependent inhibition of proliferation, induction of apoptosis, cell-cycle arrest, and terminal differentiation in DNMT3A-mutant cell lines in vitro. We show in vivo efficacy of the DOT1L inhibitor EPZ5676 in a nude rat xenograft model of DNMT3A-mutant AML. DOT1L inhibition was also effective against primary patient DNMT3A-mutant AML samples, reducing colony-forming capacity (CFC) and inducing terminal differentiation in vitro. These studies suggest that DOT1L may play a critical role in DNMT3A-mutant leukemia. With pharmacologic inhibitors of DOT1L already in clinical trials, DOT1L could be an immediately actionable therapeutic target for the treatment of this poor prognosis disease.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/enzimologia , Metiltransferases/genética , Metiltransferases/metabolismo , Terapia de Alvo Molecular , Mutação/genética , Adenosina/análogos & derivados , Adenosina/farmacologia , Adenosina/uso terapêutico , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA Metiltransferase 3A , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Histona-Lisina N-Metiltransferase , Histonas/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Lisina/metabolismo , Metilação , Camundongos Endogâmicos C57BL , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Ratos , Fatores de Tempo , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Catheter Cardiovasc Interv ; 91(6): 1159-1163, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28944572

RESUMO

OBJECTIVES: To describe a novel balloon sizing technique used during adult transcatheter patent ductus arteriosus (PDA) closure. In addition, to determine the clinical and procedural outcomes in six patients who underwent PDA balloon sizing with subsequent deployment of a PDA occluder device. BACKGROUND: Transcatheter PDA closure in adults has excellent safety and procedural outcomes. However, PDA sizing in adults can be challenging due to variable defect size, high flow state, or anatomical complexity. We describe a series of six cases where the balloon- pull through technique was successfully performed for PDA sizing prior to transcatheter closure. METHODS: Consecutive adult patients undergoing adult PDA closure at our institution were studied retrospectively. A partially inflated sizing balloon was pulled through the defect from the aorta into the pulmonary artery and the balloon waist diameter was measured. Procedural success and clinical outcomes were obtained. RESULTS: Six adult patients underwent successful balloon pull-through technique for PDA sizing during transcatheter PDA closure, since conventional angiography often gave suboptimal opacification of the defect. All PDAs were treated with closure devices based on balloon PDA sizing with complete closure and no complications. In three patients that underwent preprocedure computed tomography, the balloon size matched the CT derived measurements. CONCLUSION: The balloon pull-through technique for PDA sizing is a safe and accurate sizing modality in adults undergoing transcatheter PDA closure.


Assuntos
Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Permeabilidade do Canal Arterial/terapia , Adolescente , Adulto , Idoso , Função do Átrio Esquerdo , Cateterismo Cardíaco/efeitos adversos , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/fisiopatologia , Desenho de Equipamento , Feminino , Hemodinâmica , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular Esquerda , Adulto Jovem
14.
Catheter Cardiovasc Interv ; 92(4): 792-796, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30019833

RESUMO

OBJECTIVES: The purpose of this study is to describe the initial clinical experience with a steerable transseptal needle (STSN) for left-sided structural heart procedures. BACKGROUND: Targeted transseptal (TS) puncture is required for many structural heart procedures, and the use of a steerable needle has not previously been described. METHODS: Consecutive patients undergoing structural heart interventions with targeted TS puncture under transesophageal echocardiographic (TEE) and fluoroscopic guidance were studied. The STSN was used in all patients with a standard commercial TS sheath. Deflection of the needle was performed "real time" to achieve localization of the TS puncture site. RESULTS: Twenty-seven patients underwent STSN puncture of the interatrial septum. In all cases, the needle could be deflected in vivo to achieve optimal tenting and localization of the puncture site without having to remove or reshape the needle. The needle was deflected to match a wide range of right atrial diameters (width 4.3 ± 0.9 cm and length 6.0 ± 0.9 cm in the 4-chamber view). In two patients with prior mitral valve surgery and a fibrotic septum, assisted crossing was achieved using the piercing stylet in one patient, and Bovie energy in the other. There were no procedural complications, and all patients had successful completion of the intended structural heart procedure. CONCLUSIONS: The STSN needle can be used to target the intended puncture location on the interatrial septum with real-time adjustable deflection without the need to remove and reshape the needle. In all cases crossing was successful and there were no complications.


Assuntos
Septo Interatrial , Cateterismo Cardíaco/instrumentação , Cardiopatias/terapia , Agulhas , Idoso , Idoso de 80 Anos ou mais , Septo Interatrial/diagnóstico por imagem , Cateterismo Cardíaco/efeitos adversos , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Fluoroscopia , Cardiopatias/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Punções , Radiografia Intervencionista/métodos , Fatores de Tempo , Resultado do Tratamento
15.
Catheter Cardiovasc Interv ; 89(6): E200-E206, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27220107

RESUMO

OBJECTIVES: Our objectives were to assess for differences between standard and radiofrequency (RF) needle in procedural times, success, and spatial accuracy. BACKGROUND: Targeted transseptal (TS) puncture is essential for structural heart interventions. Spatial accuracy of standard versus RF needle has not been reported. METHODS: Consecutive patients undergoing structural heart interventions requiring TS puncture were studied retrospectively. A standard needle was alternated with a RF needle. Procedural success and times were recorded. Measurements based on intraprocedural transesophageal echocardiograms of the intended versus final TS crossing site were obtained. Pre-puncture and maximal tenting of the septum were also recorded. RESULTS: Twenty-five patients underwent standard needle and 27 RF TS access. All RF needle attempts to cross were successful without an assistance wire. Three standard needle patients required assisted crossing. After failed TS access, two patients had successful RF TS access. TS procedural times significantly favored the RF needle for time from septum to puncture (P = 0.02). Both standard and RF access yielded accurate crossing with no significant differences between the intended and actual crossing site. Maximal tenting was significantly less with the RF needle (P = 0.004). There were no major complications. CONCLUSIONS: In the hands of an experienced operator, there were no major clinically significant differences between the standard and RF needle approaches. However, procedural unassisted crossing success was higher with the RF needle approach as compared to standard needle. Procedural times and degree of septum tenting favored the RF over standard needle. Accuracy was similar with both approaches. RF was a successful strategy when standard needle failed. There were no major complications with either TS puncture strategy. © 2016 Wiley Periodicals, Inc.


Assuntos
Cateterismo Cardíaco/instrumentação , Ablação por Cateter/instrumentação , Septos Cardíacos , Agulhas , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Ablação por Cateter/efeitos adversos , Ecocardiografia Transesofagiana , Desenho de Equipamento , Feminino , Septos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Punções , Estudos Retrospectivos
16.
Catheter Cardiovasc Interv ; 86(2): 339-46, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25559345

RESUMO

In high-risk or inoperable patients, implantation of MitraClip for treatment of severe symptomatic mitral regurgitation (MR) from central (A2/P2 pathology, EVEREST patient) is effective in reducing symptoms and improving functional class. Extending the use of MitraClip to the non-EVEREST patient is of considerable interest. MitraClip implantation for wide flail segments and non-central MR is technically more challenging but represents an important and highly prevalent subset of patients. We present a case of an 82-year-old male referred to our institution for medically refractory primary MR. Trans-esophageal echocardiogram demonstrated severe (4+) MR, annular dilatation, P3 > P2 mitral valve prolapse, malcoaptation, and wide flail gaps and widths. The patient's age, frailty, chronic kidney disease, and mild cognitive impairment rendered him a candidate for MitraClip therapy. Our target area, the areas of maximum flail (A3/P3), proved too wide for grasping. Hence, the first clip was deployed medial to the target area. Subsequent deployment, in a sequential fashion ("zipper technique"), was not technically feasible due to persistent instability of the target area. Consideration was given to an alternative approach by "anchoring" our target area where the 2nd and 3rd clips were deployed lateral to the A3/P3 segment in efforts to "anchor" the maximum flail segment. This maneuver allowed final clip deployment into a more stable target area. Subsequent imaging demonstrated reduction in MR from 4+ to 1+ with preservation of a normal transmitral gradient. We report the first successful US case of four MitraClip implantation for the treatment of severe primary MR by "anchoring" flail segments.


Assuntos
Cateterismo Cardíaco/instrumentação , Insuficiência da Valva Mitral/terapia , Prolapso da Valva Mitral/terapia , Valva Mitral/fisiopatologia , Idoso de 80 Anos ou mais , Comorbidade , Ecocardiografia Doppler em Cores , Ecocardiografia Doppler de Pulso , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/fisiopatologia , Prolapso da Valva Mitral/diagnóstico , Prolapso da Valva Mitral/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Catheter Cardiovasc Interv ; 86(6): 1136-40, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25914034

RESUMO

A 47-year-old male underwent surgery for functional bicuspid aortic valve severe regurgitation with a fused right and left coronary cusp. The patient presents nine years after surgical bicuspid aortic valve repair with symptomatic severe aortic regurgitation, diagnosed by TEE and MRI, caused primarily from a perforation located at the base of the surgically fused coronary cusps. The patient had a minimally dilated aortic root that did not yet necessitate surgical intervention. We present a novel percutaneous bicuspid aortic valve perforation repair that potentially decreases the number of surgical operations the patient must undergo during his lifetime.


Assuntos
Angioplastia/instrumentação , Insuficiência da Valva Aórtica/terapia , Valva Aórtica/anormalidades , Cateterismo Cardíaco/métodos , Anuloplastia da Valva Cardíaca/efeitos adversos , Doenças das Valvas Cardíacas/cirurgia , Angioplastia/métodos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Doença da Válvula Aórtica Bicúspide , Anuloplastia da Valva Cardíaca/métodos , Ecocardiografia Transesofagiana/métodos , Seguimentos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/terapia , Medição de Risco , Dispositivo para Oclusão Septal , Resultado do Tratamento
18.
Catheter Cardiovasc Interv ; 85(6): 1066-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25413481

RESUMO

BACKGROUND: Prostanoid therapy improves quality of life and may increase survival in patients with advanced pulmonary hypertension (PH). Balloon dilated atrial septostomy (BDAS) can palliate or bridge to transplantation for patients resistant to medical therapy. The safety and efficacy of BDAS in the prostanoid era has not previously been reported. METHODS: All patients had progressive symptoms despite prostanoid therapy at the time of their first BDAS. Sixteen patients who underwent a total of 23 septostomies between 2004 and 2014 were included in this retrospective case series. RESULTS: Patients were aged 47.6 years ± 11.3 with 12/16 women. Etiologies included idiopathic (7), methamphetamine (6), scleroderma (1), and anorexigen (2). One patient died within 24 hr post-procedure. Thirty-day and 1-year survival were 75% and 64%, respectively. Six of the septostomies were revisions, including two which were ultimately stented. Three subjects were successfully bridged to transplant. Pulmonary capillary wedge pressure (PCWP) increased from a mean of 13 to 17 mm Hg, cardiac index increased from 2.1 to 2.4 L/min/m(2) , and arterial saturation decreased from 90.7 ± 4.3 to 82.5 ± 5.6%. All non-survivors at 30 days were male and had higher baseline serum creatinine, mean RAP, right ventricular end diastolic pressure (RVEDP), and left ventricle (LV) filling pressures, and lower right ventricle (RV) ejection fraction. Mortality was associated with unchanged post-septostomy cardiac output despite an increase in left ventricular end diastolic pressure (LVEDP). CONCLUSIONS: BDAS may be an alternate therapy for select PH patients who have symptomatic progression despite prostanoid therapy. Survival is comparable to prior reports of BDAS in the pre-prostanoid era.


Assuntos
Cateterismo Cardíaco/métodos , Septos Cardíacos/cirurgia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Prostaglandinas/uso terapêutico , Circulação Pulmonar/fisiologia , Adulto , Estudos de Coortes , Feminino , Átrios do Coração/diagnóstico por imagem , Septos Cardíacos/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Ultrassonografia
19.
Catheter Cardiovasc Interv ; 85(1): 13-22, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24753053

RESUMO

OBJECTIVES: To characterize the prevalence of thrombus burden, collateral vessels to the infarct-related artery, epicardial coronary artery flow, and myocardial perfusion in patients with angiographically confirmed definite stent thrombosis (ST), and to define their relationship with associated treatments and outcomes. BACKGROUND: Angiographic characteristics of ST are not well defined. METHODS: All cases of angiographically determined ST at five academic hospitals from 2005 to 2012 were reviewed. Demographic, procedural, and angiographic characteristics were recorded. In-hospital and 1-year follow-up data were obtained. RESULTS: Among 205 cases of angiographic definite ST (60 ± 8 years; 87% male), the majority presented with late/very late ST (69%) and STEMI (66%). High-risk angiographic findings at presentation included thrombus grade 4-5 (87%), absence of collateral vessels (76%), and reduced initial TIMI 3 flow (90%). Final TIMI 3 flow was achieved in 90% of patients and was associated with greater use of aspiration thrombectomy (60% vs. 25%; P = 0.003), glycoprotein IIb/IIIa inhibitors (80% vs. 30%, P < 0.001), and repeat stenting (67% vs. 10%, P < 0.001). A final myocardial perfusion grade of 2-3 was achieved in 79% of patients and was associated with greater use of aspiration thrombectomy (61% vs. 36%, P = 0.003). After multivariable logistic regression, aspiration thrombectomy (AOR 2.6, 95% CI 1.3-5.2) and implantation of a new stent (AOR 2.1, 95% CI 1.1-4.3) were associated with optimal combined epicardial flow and myocardial perfusion. At 1-year follow-up, significantly lower risk of repeat ST (HR 0.1; 95% CI 0.1,0.2; P < 0.001) among patients with initial TIMI 3 flow at index ST was observed. CONCLUSIONS: The majority of ST patients present with late/very late ST with high thrombus burden and STEMI. Presence of collateral vessels and low thrombus burden is cardioprotective, while reduced initial TIMI flow is associated with larger infarct size and recurrent ST. Aspiration thrombectomy and repeat stenting are associated with improved epicardial coronary artery flow and myocardial perfusion among patients treated for ST. © 2014 Wiley Periodicals, Inc.


Assuntos
Circulação Colateral , Angiografia Coronária , Circulação Coronária , Trombose Coronária/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Intervenção Coronária Percutânea/efeitos adversos , Stents , Centros Médicos Acadêmicos , Idoso , Velocidade do Fluxo Sanguíneo , California , Distribuição de Qui-Quadrado , Trombose Coronária/etiologia , Trombose Coronária/fisiopatologia , Trombose Coronária/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Intervenção Coronária Percutânea/instrumentação , Valor Preditivo dos Testes , Fatores de Proteção , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Sucção , Trombectomia/métodos , Resultado do Tratamento
20.
Curr Opin Cardiol ; 29(2): 133-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24434578

RESUMO

PURPOSE OF REVIEW: Functional tricuspid regurgitation (FTR) is an important clinical entity that is encountered frequently during the operative management of left-sided heart valve disease, particularly in the setting of mitral regurgitation. Failure to recognize the importance of FTR during mitral valve surgery may result in inferior early and late outcomes because of the progression of tricuspid regurgitation and right heart failure. In this review, attention is focused on recent literature, which increasingly supports the use of corrective tricuspid valve annuloplasty, and the growing consensus that FTR or tricuspid annular dilation should be more aggressively addressed at the time of cardiac surgery. RECENT FINDINGS: The European Society of Cardiology and the European Association for Cardiothoracic Surgery (ESC/EACTS) 2012 guidelines recommend a more proactive approach to tricuspid regurgitation correction and highlight the shifting consensus toward more aggressive surgical therapy. Rigid annuloplasty rings should be used in favor of flexible bands or DeVega-style repairs. Preoperative determinants of clinical outcomes now include echocardiographic parameters of tricuspid valve tenting area, and associated right ventricular size and function. SUMMARY: Despite data demonstrating inferior outcomes in the presence of residual tricuspid regurgitation after cardiac surgery, surgical repair for FTR appears to be underutilized. Increased recognition and correction of tricuspid regurgitation at the time of surgery is increasingly supported by published guidelines, although randomized prospective data are needed to bolster current recommendations.


Assuntos
Anuloplastia da Valva Cardíaca , Sistema de Registros , Insuficiência da Valva Tricúspide/cirurgia , Animais , Ecocardiografia , Humanos , Insuficiência da Valva Mitral/cirurgia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Insuficiência da Valva Tricúspide/fisiopatologia
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