Alan W Heldman

University of Miami Miller School of Medicine, Miami, Florida, United States

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Publications (77)534.34 Total impact

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    Journal of the American College of Cardiology 03/2014; 63((12_S)):A-1670. · 14.09 Impact Factor
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    ABSTRACT: OBJECTIVE. We explored the efficacy, safety, and clinical consequences of on-label and off-label TAVR in the real-world setting.BACKGROUND.The transcatheter heart valve (THV) was initially approved only for transfemoral (TF) delivery (on-label use) during transcatheter aortic valve replacement (TAVR) in inoperable patients with severe aortic stenosis. Because of lack of alternative options in TAVR-eligible patients with inadequate TF access, other routes have been utilized for THV implantation (off-label use), outcomes of which were previously unknown.METHODS.Consecutive patients with severe inoperable AS who underwent clinical TAVR at our site were enrolled in a prospective database. Fifty subjects underwent TF-TAVR (on-label group), while non-TF routes were utilized in 60 subjects (off-label group). Procedural events, 30-day clinical outcomes, and 1-year all-cause mortality data were analyzed.RESULTS.Technical device success was similar between on-label and off-label groups (88% vs. 87%, respectively; P=0.92), as was the incidence of procedural complications and 30-day clinical events. The on-label group had lower 1-year all-cause death rate (12%) compared to the off-label group (32%; P=0.02). The 1-year all-cause mortality in the off-label group was comparable to published clinical trial and registry data on TAVR, and appeared lower than historical outcomes with conservative medical therapy.CONCLUSION.On-label use of the THV in the real-world setting was associated with favorable survival outcomes compared to off-label TAVR and historical data. Off-label use of the THV appeared to be safe and effective when used in select patients with inoperable AS who are not eligible for TAVR via TF approach. © 2014 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 03/2014; · 2.51 Impact Factor
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    ABSTRACT: While accumulating data support the efficacy of intramyocardial cell-based therapy to improve LV function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including: reducing fibrosis, neoangiogenesis and neomyogenesis. To test the hypothesis that the impact on cardiac structure and function following intramyocardial injections of autologous MSCs results from a concordance of pro-recovery phenotypic effects. Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness and contractility at baseline, 3, 6 and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LVEF (+9.4±1.7%, p=0.0002) and decreased scar mass (-47.5±8.1%; p<0.0001) compared to baseline. MSC-injected segments had concordant reduction in scar size, perfusion and contractile improvement (concordant score: 2.93±0.07), whereas revascularized (0.5±0.21) and non-treated segments (-0.07±0.34) demonstrated non-concordant changes (p<0.0001 vs. injected segments). Intramyocardial injection of autologous MSCs into akinetic yet non-revascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive due to lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications. Clinical Trial Registration: NCT00587990 URL: http://clinicaltrials.gov/show/NCT00587990.
    Circulation Research 02/2014; · 11.86 Impact Factor
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    ABSTRACT: Transendocardial Stem Cell Injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the impact of the injection site remains unknown. To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in non-injected segments. Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13-months after TESI. Segmental early enhancement defect (SEED, a measure of scar size) was reduced by TESI in both injected (-43.7±4.4%, n=95, p<0.01) and non-injected segments (-25.1±7.8%, n=148, p<0.001; between group comparison p<0.05). Conversely, segmental ejection fraction (SEF, a measure of contractility) improved in injected scar segments (19.9±3.3 to 26.3±3.5%, p=0.003) but not in non-injected scar segments (21.3±2.6 to 23.5±3.2%, p=0.20, between group comparison p<0.05). In the subgroup of scar segments with baseline SEF<20%, the SEF improvement was even greater in injected segments (12.1±1.2% to 19.9±2.7%, n=18, p=0.003) vs. non-injected segments (13.3±1.3% to 16.1±2.1%, n=15, p=0.05; between group comparison p<0.05). These findings illustrate a dichotomy in regional responses to TESI. Although scar reduction was evident at the site of TESI and remotely, ventricular functional responses occurred preferentially at the sites of TESI. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.
    Circulation Research 01/2014; · 11.86 Impact Factor
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    ABSTRACT: Objective: To assess the impact of the Centers for Medicare and Medicaid Services (CMS) national coverage determination (NCD) on access for patients with aortic stenosis (AS) with Transcatheter Aortic Valve Replacement (TAVR) in a tertiary care center. Background: TAVR has given hope to patients with AS who are deemed inoperable. The effects of the NCD on access to patients with AS has not been evaluated. Materials and Methods: A total of 94 inoperable AS patients were evaluated and treated from December 2011 through June of 2012 with TAVR. Patients who underwent transfemoral (TF) vs. non-TF access were compared. The CMS NCD was released on May 1, 2012 and on July 1, 2012, the non-transfemoral access program was put on hold due to lack of reimbursement. Results: Patients in the TF (n= 33) and non-TF access (n=61) groups were similar in age (85.2±6.3 vs. 84.8±6.6 p=0.74) and STS mortality (9.38 ±5.33 vs. 7.91 ±3.69, p=0.074). The iliofemoral arteries were larger diameter in the TF group (7. 72±1.49 vs. 6.21±1.78, p<0.001) and males (7.39 ± 1.81 vs. 6.1 ±1.61 P<0.001). More women underwent valve implantation via non-TF access (73% vs. 23%, p=0.03). After the NCD, 21 patients who previously qualified for non-TF TAVR would not be reimbursed by CMS. Four died soon after. and report 4 patient deaths that are explicitly linked to this coverage decision. Conclusions: After the NCD, the proportion of inoperable patients with severe AS that can be treated with TAVR was greatly reduced due the lack of reimbursement for TAVR via non-TF access. This effect is particularly pronounced in women. © 2014 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 01/2014; · 2.51 Impact Factor
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    ABSTRACT: Objectives To determine the incidence of new-onset atrial fibrillation (AF) associated with different methods of isolated aortic valve replacement (AVR): transfemoral (TF-), transapical (TA-) and transaortic (TAo-) catheter-based valve replacement and conventional surgical approaches. Background The relative incidences of AF associated with the various access routes for AVR have not been well characterized. Methods In this single-center, retrospective cohort study, we evaluated a total of 231 consecutive patients undergoing AVR for degenerative aortic stenosis (AS) between March 2010 and September 2012. Patients with a history of either paroxysmal, persistent, or chronic AF, with bicuspid aortic valves, and patients who expired within 48 hours after AVR were excluded. A total of 123 patients (53% of total group) qualified for inclusion. Data on documented episodes of new-onset AF, along with all clinical, echocardiographic, procedural and 30-day follow up data, were collated. Results AF occurred in 52 patients (42.3%). AF incidence varied according to the procedural method. AF occurred in 60% of patients undergoing surgical AVR (SAVR), 53% after TA-TAVR, 33% after TAo-TAVR cases and 14% after TF-TAVR. The episodes occurred at a median time interval of 53 (41,87) hours after completion of the procedure. Procedures without pericardiotomy had 82% risk reduction of AF when compared with those with pericardiotomy (adjusted OR 0.18 (95% CI 0.05-0.59)). Conclusion AF is a common complication of AVR with a cumulative incidence of >40% in elderly patients with degenerative AS who underwent either SAVR or TAVR. AF was most common with SAVR and least common with TF-TAVR. Procedures without pericardiotomy were associated with a lower incidence of AF.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
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    ABSTRACT: Transcatheter aortic valve implantation (TAVI) for failing aortic root and valve homografts has been described primarily via a transapical approach. We report the successful treatment of two patients with failing homografts by transfemoral (TF) TAVI. In both cases, TF TAVI was accomplished without technical difficulty and with good clinical outcomes.
    Journal of Cardiac Surgery 12/2013; · 1.35 Impact Factor
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    ABSTRACT: IMPORTANCE Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. OBJECTIVE To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. DESIGN, SETTING, AND PATIENTS A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. INTERVENTIONS Injections in 10 LV sites with an infusion catheter. MAIN OUTCOMES AND MEASURES Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. RESULTS No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. CONCLUSIONS AND RELEVANCE Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00768066.
    JAMA The Journal of the American Medical Association 11/2013; · 29.98 Impact Factor
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    ABSTRACT: Objective: To study rotational atherectomy (RA) outcomes in patients undergoing high-risk PCI randomized to receive hemodynamic support using either IABP or Impella 2.5 in the PROTECT II trial. Background: RA of heavily calcified lesions is often necessary for complex PCI but can be associated with slow-flow, hypotension and higher risk of periprocedural MI Methods: We compared baseline, angiographic, procedural characteristics and outcomes of patients treated with and without RA. We examined also RA technique and outcomes. Results: RA was used in 52 of 448 patients (32 with Impella vs 20 with IABP, P = 0.08). RA patients were older (72 vs. 67 yo, P = 0.0009), more likely to have prior CABG (48 vs. 32%, P = 0.017), higher STS (8.1 vs. 5.7, P = 0.012) and higher SYNTAX scores (37 vs. 29, P < 0.0001). At 90 days, RA use was associated with higher incidence of MI but no mortality difference. RA was used more aggressively with Impella resulting in higher rate of periprocedural MI (P < 0.01), with no difference in mortality between groups (P = 0.78). Repeat revascularization occurred less frequently with Impella (P < 0.001). There were no differences in 90-day major adverse events between IABP and Impella in patients undergoing RA (P = 0.29). In patients not treated with RA, fewer MAEs were observed with Impella compared to IABP (P = 0.03). Conclusions: Patients who were treated with RA had more comorbidities, and more complex and extensive coronary artery disease. In patients with Impella, more aggressive RA use resulted in fewer revascularization events but higher incidence of periprocedural MI. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 10/2013; · 2.51 Impact Factor
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    ABSTRACT: Objective: To assess the feasibility and outcomes in patients undergoing transvenous transseptal (TS) transcatheter aortic valve replacement (TAVR). Background: TS approach for TAVR was abandoned in favor of retrograde transfemoral, transaortic or transapical approaches. TS TAVR may still be warranted in patients for whom no other approach is feasible. Methods: Observational consecutive case series at a single center, to evaluate technical outcomes in inoperable patients with aortic stenosis who had contraindications for other approaches and who underwent TAVR via a transvenous TS antegrade approach using the Edwards-Sapien (ES) valve. Results: Over a 4-month period, 9 patients underwent TS TAVR with 26mm (n=4) and 23mm (n=5) ES valves. Mean age was 84.5±6.6 years and Society of Thoracic Surgeons predicted risk of mortality was 7.8 ± 2.8%. Specific contraindications for other access included iliofemoral arterial diameter < 7mm in 9 (100%), porcelain aorta in 6 (66%) patients, multiple (≥2) sternotomies in 2 (22%) patients, severe pulmonary disease in 3 (33%), extreme frailty in 1 (11%), spinal stenosis with impaired ability to rehabilitate post-surgery in 1 (11%) and apical left ventricular thrombus in 1 (11%) patient. Antegrade deployment of the ES prosthetic valve was technically feasible in 8 patients. Major bleeding occurred in 4 patients, two patients suffered acute kidney injury without need for dialysis and one patient required a permanent pacemaker. The median (25(th) , 75(th) percentiles) fluoroscopy time was 49 (34, 81) minutes and contrast volume was 150 (120, 225) ml. No patient had hemodynamically significant post-TAVR aortic insufficiency nor damage to the mitral valve. At 6 months follow-up, there were no cerebrovascular events or rehospitalizations and mean NYHA Class improved from 3.4 to 1.7. Conclusions: The antegrade TS approach to TAVR is a technically feasible option for "no-access" patients. Prospective assessment of the safety and efficacy of this approach in the current era warrants further study. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 06/2013; · 2.51 Impact Factor
  • Joshua M Hare, Darcy Difede, Alan W Heldman
    JAMA The Journal of the American Medical Association 04/2013; 309(14):1458-9. · 29.98 Impact Factor
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    ABSTRACT: BACKGROUND: A large proportion of candidates for transcatheter aortic valve replacement (TAVR) have inadequate ileofemoral vessels for transfemoral (TF) access. The transapical route (TAP) is the current alternative, but is associated with less favorable outcomes. Other access options need to be explored. OBJECTIVES: We investigated the technical feasibility and safety of the transaortic (TAO) TAVR approach in patients not eligible for TF access, using the commercially-available device (Edwards SAPIEN® valve) in the United States. METHODS: Forty-four consecutive patients with severe, inoperable aortic stenosis (AS) underwent TAO TAVR in our institution. Procedural and 30-day clinical outcomes data were compared with 76 consecutive patients who underwent TAP TAVR at our site. Technical learning curves were assessed by comparing outcomes of the first 20 cases with the subsequent patients who underwent each procedure. RESULTS: The TAO and TAP TAVR groups were similar in terms of VARC-defined device success (89% vs. 84%; P=0.59) and rates of the 30-day combined safety endpoint of all-cause mortality, myocardial infarction, major stroke, disabling bleeding, severe acute kidney injury, and valve re-intervention (20% vs. 33%; P=0.21). The TAO approach, compared to TAP TAVR, was associated with lower combined bleeding and vascular event rate (27% vs. 46%; P=0.05), shorter median ICU length of stay (3 vs. 6 days; P=0.01), and a favorable learning curve. CONCLUSION: TAVR via the TAO approach is technically feasible, appears to be associated with favorable outcomes, and expands the current alternative options for access sites in inoperable AS patients who are ineligible for TF TAVR.
    Journal of the American College of Cardiology 04/2013; · 14.09 Impact Factor
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    ABSTRACT: Objective: To determine the impact of suture-mediated vascular closure devices on net adverse clinical events (NACE) after balloon aortic valvuloplasty (BAV). Background: Ischemic and bleeding complications are common following transfemoral BAV however; previous studies have been single center and limited by varying definitions of major bleeding. Methods: The Effect of Bivalirudin on Aortic Valve Intervention Outcomes (BRAVO) study was a retrospective observational study conducted at two high-volume academic centers over a 6-year period designed to compare the effect of bivalirudin versus unfractionated heparin. This is a sub-analysis of 428 consecutive patients who underwent BAV (with 10-13 French sheaths) to compare the effect of hemostasis with vascular closure devices versus manual compression utilizing standardized definitions. NACE was defined as the composite of major bleeding and major adverse clinical events (MACE). All events were adjudicated by an independent clinical events committee who were blinded to antithrombin use. Results: Pre-closure was performed in 269 (62.8%) of patients. While bivalirudin was used more frequently in those with pre-closure (60.6% vs. 37.7%, p<0.001), a history of prior BAV (11.1% vs. 3.6%, p=0.04) and peripheral vascular disease (30.7% vs. 19.7%, p=0.01) was more common in those not undergoing pre-closure (n=159, 37%). Other clinical and demographic features were well balanced between groups. Vascular closure was associated with a significant reduction in NACE (24.5% vs 10.0% p<0.001). Results remained significant after adjusting for baseline differences and bivalirudin use (OR 0.38, 95% CI: 0.21 - 0.68; p=0.001). Conclusions: Our study suggests that suture-mediated vascular closure is associated with a substantial reduction in NACE after transfemoral BAV. Large randomized clinical trials should be conducted to confirm our results. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 02/2013; · 2.51 Impact Factor
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    ABSTRACT: BACKGROUND: With the expansion in the use of transcatheter valve therapies for aortic stenosis, the incidence of hemodynamically significant paravalvular regurgitation (PVR) has become a clinical challenge. METHODS: The study population consisted of those patients with either acute significant PVR immediately post-Edwards SAPIEN (ES) aortic valve implantation, requiring additional maneuvers during the index transcatheter aortic valve replacement (TAVR) or symptomatic PVR requiring treatment by transcatheter closure at a later date. All the patients were assessed within 24 hrs, 30 days, 3 months, 6 months and 12 months after the procedure. RESULTS: A total of 100 consecutive patients underwent ES TAVR (62% with 23 mm and 38% with 26 mm valve), of them 27% (27/100) were identified to have hemodynamically significant PVR requiring additional percutaneous interventions during or after the index procedure. Patient's mean age was 85 ± 12 years and 74% (20/27) were male. The mean Society of Thoracic Surgeon Score was 11.3% (range 4.6-17.6%), 59% had a 23 mm and 41% had a 26 mm ES valve. There was no difference in the occurrence of PVR between a) two valve sizes-23 mm (16/62) vs. 26 mm (11/38) (P = 0.817) and b) the two approaches-transfemoral (15/48) vs. transapical (TA) (12/52) (P = 0.37). A total of 32 procedures were performed on the 27 patients: one patient required four and two required two procedures each. There were 19 repeat ballooning, seven valve in valve and six transcatheter device closure procedures. The approach was retrograde in 66%, antegrade transeptal in 6% and antegrade TA in 28%. The procedural success rate was 90.6%, the total 30-day, 3 months and 6 months mortality rate was 7.4, 18.5, and 22% respectively. At the time of final analysis a total of 56% (15/27) had completed a 12 month follow-up. CONCLUSION: The management of PVR in the TAVR era is a technical challenge. We present our experience and propose a management approach. © 2013 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 01/2013; · 2.51 Impact Factor
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    ABSTRACT: BACKGROUND: Intramyocardial injection of mesenchymal stem cells (MSCs) in chronic ischemic cardiomyopathy is associated with reverse remodeling in experimental models and humans. Here, we tested the hypothesis that allogeneic MSC therapy drives ventricular remodeling by producing durable and progressive scar size reduction in ischemic cardiomyopathy. METHODS AND RESULTS: Gottingen swine (n=12) underwent left anterior descending coronary artery myocardial infarction (MI), and 3 months post-MI animals received either intramyocardial allogeneic MSC injection (200 mol/L cells; n=6) or left ventricle (LV) catheterization without injection (n=6). Swine were followed with serial cardiac magnetic resonance imaging for 9 months to assess structural and functional changes of the LV. Intramyocardial injection was performed using an integrated imaging platform combining electroanatomical mapping unipolar voltage and 3-dimensional cardiac magnetic resonance imaging angiography-derived anatomy to accurately target infarct border zone injections. MSC-treated animals had a 19.62±2.86% reduction in scar size at 3 months postinjection, which progressed to 28.09±2.31% from 3 to 6 months postinjection (P<0.0001). MSC-treated animals had unchanged end-diastolic volume (EDV; P=0.08) and end-systolic volume (ESV; P=0.28) from preinjection to 6 months postinjection, whereas controls had progressive dilatation in both EDV (P=0.0002) and ESV (P=0.0002). In addition, MSC-treated animals had improved LV sphericity index. Percentage change in infarct size correlated with percentage change in EDV (r=0.68; P=0.01) and ESV (r=0.77; P=0.001). Ejection fraction increased from 29.69±1.68% to 35.85±2.74% at 3 months post-MSC injection and progressed to 39.02±2.42% 6 months postinjection (P=0.0001), whereas controls had a persistently depressed ejection fraction during follow-up (P=0.33). CONCLUSION: Intramyocardial injection of allogeneic MSCs leads to a sustained and progressive reduction in infarct size, which in turn drives reverse remodeling and increases in ejection fraction. These findings support ongoing biological activity of cell therapy for substantial periods and suggest optimal end points for future clinical trials.
    Journal of the American Heart Association. 01/2013; 2(3):e000140.
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    ABSTRACT: Transcatheter aortic valve replacement is an increasingly common treatment of critical aortic stenosis. Many aortic stenosis patients have concomitant left ventricular dysfunction, which can instigate the formation of thrombus resistant to anticoagulation. Recent trials evaluating transcatheter aortic valve replacement have excluded patients with left ventricular thrombus. We present a case in which an 86-year-old man with known left ventricular thrombus underwent successful transcatheter aortic valve replacement under cerebral protection.
    Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 01/2013; 40(4):477-480. · 0.67 Impact Factor
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    ABSTRACT: WEBSITE FEATURE.
    Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 01/2013; 40(3):364-6. · 0.67 Impact Factor
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    ABSTRACT: BACKGROUND: As mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit+ cardiac stem cells (CSCs) in vivo and in vitro, we hypothesized that combining human (h)MSCs with c-kit+ hCSCs produces greater infarct size reduction compared to either cell administered alone after MI. METHODS AND RESULTS: Yorkshire swine underwent balloon occlusion of the LAD coronary artery followed by reperfusion, and were immunosuppressed after MI with cyclosporine and methylprednisolone. Intramyocardial injection of either: combination hCSCs/hMSCs (1M/200M, n=5), hCSCs alone (1M, n=5), hMSCs alone (200M, n=5), or placebo (PBS, n=5) was administered to the infarct border zones at 14 days post-MI. Phenotypic response to cell therapy was assessed by cardiac MRI and micromanometer conductance catheterization hemodynamics. While each cell therapy group had reduced MI size relative to placebo (p<0.05), the MI size reduction was 2-fold greater in combination vs. either cell therapy alone (p<0.05). Accompanying enhanced MI size reduction was substantial improvement in LV chamber compliance (end-diastolic pressure volume relationship, p<0.01) and contractility (preload recruitable stroke work and dP/dt(max), p<0.05) in combination treated swine. EF was restored to baseline in cell treated pigs, while placebo pigs had persistently depressed LV function (p<0.05). Immunohistochemistry showed 7-fold enhanced engraftment of stem cells in the combination therapy group vs. either cell type alone (P<0.001). CONCLUSIONS: Combining hMSCs and hCSCs as a cell therapeutic enhances scar size reduction, and restores diastolic and systolic function toward normal after MI. Taken together these findings illustrate important biological interactions between c-kit+ CSCs and MSCs that enhance cell-based therapeutic responses.
    Circulation 12/2012; · 15.20 Impact Factor
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    ABSTRACT: CONTEXT Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. OBJECTIVE To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. DESIGN, SETTING, AND PATIENTS A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. INTERVENTION Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. MAIN OUTCOME MEASURES Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak $$⋅VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. RESULTS Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise $$⋅VO2 max. Allogeneic and autologous MSCs reduced mean EED by -33.21% (95% CI, -43.61% to -22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. CONCLUSIONS In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01087996.
    JAMA The Journal of the American Medical Association 11/2012; · 29.98 Impact Factor
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    ABSTRACT: Transcatheter aortic valve replacement (TAVR) is currently a therapeutic alternative to open aortic valve replacement for high-risk patients with severe symptomatic aortic valve stenosis. The procedure is associated with some life-threatening complications including circulatory collapse which may require temporary hemodynamic support. We describe our experience with the use of Impella 2.5 system to provide emergent left ventricular support for hemodynamic collapse in patients after TAVR with Edwards SAPIEN prosthesis. © 2012 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 08/2012; · 2.51 Impact Factor

Publication Stats

3k Citations
534.34 Total Impact Points

Institutions

  • 2008–2014
    • University of Miami Miller School of Medicine
      • • Division of Hospital Medicine
      • • Cardiovascular Division
      • • Department of Radiology
      Miami, Florida, United States
  • 1970–2009
    • University of Miami
      • Miller School of Medicine
      Coral Gables, FL, United States
  • 2002–2008
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, MD, United States
  • 2000–2006
    • Johns Hopkins Medicine
      • • Division of Cardiology
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2004
    • University of Leicester
      Leiscester, England, United Kingdom