Petros Okubagzi

Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study.

OBJECTIVES We conducted a pilot study to evaluate the feasibility of transendocardial delivery of autologous bone marrow (ABM) strategy in patients with severe symptomatic chronic myocardial ischemia not amenable to conventional revascularization. BACKGROUND Transendocardial injection of ABM cells appears to enhance perfusion of ischemic porcine myocardium. METHODS Ten patients underwent transendocardial injection of freshly aspirated and filtered unfractionated ABM using left ventricular electromechanical guidance. Twelve injections of 0.2 ml each were successfully delivered into ischemic noninfarcted myocardium pre-identified by single-photon emission computed tomography perfusion imaging. RESULTS Autologous bone marrow injection was successful in all patients and was associated with no serious adverse effects; in particular, there was no arrhythmia, evidence of infection, myocardial inflammation, or increased scar formation. Two patients were readmitted for recurrent chest pain. At three months, Canadian Cardiovascular Society angina score significantly improved (3.1 +/- 0.3 vs. 2.0 +/- 0.94, p = 0.001), as well as stress-induced ischemia occurring within the injected territories (2.1 +/- 0.8 vs. 1.6 +/- 0.8, p < 0.001). Treadmill exercise duration, available in nine patients, increased, but the change was not significant (391 +/- 155 vs. 485 +/- 198, p = 0.11). CONCLUSIONS This study provides preliminary clinical data indicating feasibility of catheter-based transendocardial delivery of ABM to ischemic myocardium.

Complications and Outcome of Balloon Aortic Valvuloplasty in High-Risk or Inoperable Patients

OBJECTIVES This study aimed to determine the success, complications, and survival of patients after balloon aortic valvuloplasty (BAV). BACKGROUND The introduction of transcatheter aortic valve implantation (TAVI) BAV has led to a revival in the treatment of patients with severe aortic stenosis. METHODS A cohort of 262 patients with severe aortic stenosis underwent 301 BAV procedures. Of these, 39 (14.8%) patients had ≥2 BAV procedures. Clinical, hemodynamic, and follow-up mortality data were collected. RESULTS The cohort mean age was 81.7 ± 9.8 years, and the mean Society of Thoracic Surgeons and logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 13.3 ± 6.7 and 45.6 ± 21.6, respectively. BAV was performed as a bridge to TAVI or to surgical aortic valve replacement in 28 patients (10.6%) and for symptom relief in 234 (89.4%). The mean aortic valve area (AVA) increased from 0.58 ± 0.3 cm(2) to 0.96 ± 0.3 cm(2) (p < 0.001). Of these, 111 (45.0%) had final AVA >1 cm(2), and in 195 patients (79%), AVA increased by >40%. De novo BAV resulted in a higher mean increase in AVA 0.41 ± 0.24 cm(2) versus 0.28 ± 0.24 cm(2) in redo BAV (p = 0.003). Serious adverse events occurred in 47 patients (15.6%), intraprocedural death in 5 (1.6%), stroke in 6 (1.99%), coronary occlusion in 2 (0.66%), severe aortic regurgitation in 4 (1.3%), resuscitation/cardioversion in 5 (1.6%), tamponade in 1 (0.33%), and permanent pacemaker in 3 (0.99%). A vascular complication occurred in 21 patients (6.9%); 34 (11.3%) had a post-procedure rise in creatinine >50%; and 3 (0.99%) required hemodialysis. During median follow-up of 181 days, the mortality rate was 50% (n = 131). The mortality rate in the group with final AVA >1 cm(2) was significantly lower than in the group with final AVA of <1 cm(2) (36.4% vs. 57.9%, p < 0.001). Final AVA was associated with lower mortality (hazard ratio: 0.46, p = 0.03). BAV as a bridge to TAVI or surgical aortic valve replacement had a better outcome compared with BAV alone: mortality rate 7 (25%) versus 124 (52.9%), respectively (p < 0.0001). CONCLUSIONS Long-term survival is poor after BAV alone. BAV as a bridge to percutaneous or surgical aortic valve replacement is feasible, safe, and associated with better outcome than BAV alone.

Clinical profile, prognostic implication, and response to treatment of pulmonary hypertension in patients with severe aortic stenosis.

The incidence, correlates, and prognostic implications of pulmonary hypertension (PH) are unclear in patients with severe aortic stenosis (AS). We studied 509 patients with severe AS evaluated for transcatheter aortic valve implantation (TAVI). Patients were divided into groups based on pulmonary artery systolic pressure (PASP): group I, 161 (31.6%) with PASP <40 mm Hg; group II, 175 (34.3%) with PASP 40 to 59 mm Hg; and group III, 173 (33.9%) with PASP ≥ 60 mm Hg. Group III patients were more symptomatic and had higher creatinine levels and higher left ventricular end-diastolic pressure. Transpulmonary gradient was >12 mm Hg in 17 patients (10.5%), 31 patients (17.7%), and 80 patients (46.2%) in groups I through III, respectively. In a median follow-up of 202 days (73 to 446) mortality rates were 35 (21.7%), 69 (39.3%), and 85 (49.1%) in groups I through III, respectively (p <0.001). Immediately after TAVI, in patients with PASP >40 mm Hg there was significant decrease in PASP (63.1 ± 16.2 to 48.8 ± 12.4 mm Hg, p <0.0001), which remained at 1 year (50.1 ± 13.1 mm Hg, p = 0.04). After surgical aortic valve replacement there was a significant immediate decrease in PASP (66.1 ± 16.3 to 44.7 ± 14.2 mm Hg, p <0.0001), which persisted at 3 to 12 months (44.8 ± 20.1 mm Hg, p <0.001). In patients who underwent balloon aortic valvuloplasty, PASP decreased immediately after the procedure (63.2 ± 14.8 to 51.8 ± 17.1 mm Hg, p <0.0001), yet at 3 to 12 months pressure returned to baseline levels (57.4 ± 17.0 mm Hg, p = 0.29). In conclusion, patients with severe AS have a high prevalence of PH, and in patients with severe AS increased PASP is associated with increased mortality. Surgical aortic valve replacement and TAVI are effective treatments for these patients and result in a significant PASP decrease.

Correlates and Causes of Death in Patients With Severe Symptomatic Aortic Stenosis Who Are Not Eligible to Participate in a Clinical Trial of Transcatheter Aortic Valve Implantation

Background— Transcatheter aortic valve implantation is currently being evaluated in patients with severe aortic stenosis who are considered high-risk surgical candidates. This study aimed to detect incidences, causes, and correlates of mortality in patients ineligible to participate in transcatheter aortic valve implantation studies. Methods and Results— From April 2007 to July 2009, a cohort of 362 patients with severe aortic stenosis were screened and did not meet the inclusion/exclusion criteria necessary to participate in a transcatheter aortic valve implantation trial. These patients were classified into 2 groups: group 1 (medical): 274 (75.7%): 97 (35.4%) treated medically and 177 (64.6%) treated with balloon aortic valvuloplasty; and group 2 (surgical): 88 (24.3%). The medical/balloon aortic valvuloplasty group had significantly higher clinical risk compared with the surgical group, with significantly higher Society of Thoracic Surgeons score (12.8±7.0 versus 8.5±5.1; P<0.001) and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (42.4±22.8 versus 24.4±18.1; P<0.001). The medical/balloon aortic valvuloplasty group had a higher New York Heart Association functional class, incidence of renal failure, and lower ejection fraction. During median follow-up of 377.5 days, mortality in the medical/balloon aortic valvuloplasty group was 102 (37.2%), and during median follow-up of 386 days, mortality in the surgical group was 19 (21.5%). Multivariable adjustment analysis identified renal failure (hazard ratio [HR]: 5.60), New York Heart Association class IV (HR: 5.88), and aortic systolic pressure (HR: 0.99) as independent correlates for mortality in the medical group, whereas renal failure (HR: 7.45), Society of Thoracic Surgeons score (STS; HR: 1.09) and logistic EuroSCORE (HR: 1.45) were correlates of mortality in the in the surgical group. Conclusion— Patients with severe symptomatic aortic stenosis not included in transcatheter aortic valve implantation trials do poorly and have extremely high mortality rates, especially in nonsurgical groups, and loss of quality of life in surgical groups.

Comparison between Society of Thoracic Surgeons Score and logistic EuroSCORE for predicting mortality in patients referred for transcatheter aortic valve implantation

BACKGROUND The primary inclusion criteria from both the Society of Thoracic Surgeons (STS) score and the logistic EuroSCORE are currently used to identify high-risk and inoperable patients eligible for transcatheter aortic valve implantation (TAVI). We aimed to examine the correlation between STS and logistic EuroSCOREs and their performance characteristics in patients referred for TAVI. METHODS The study cohort consisted of 718 high-risk patients with severe aortic stenosis who were considered for participation in a TAVI clinical trial. The performance of the STS and logistic EuroSCOREs was evaluated in three groups: (a) medical management or balloon aortic valvuloplasty (BAV), 474 (66%); (b) 133 patients (18.5%) with surgical aortic valve replacement (AVR); (c) 111 (15.4%) with TAVI. The mean age was 81.8 ± 8.1 years, and 394 (54.8%) were female. RESULTS The mean STS score was 11.5 ± 6.1, and the mean logistic EuroSCORE was 39.7 ± 23.0. Pearson correlation coefficient showed moderate correlation between the STS and logistic EuroSCOREs (r = 0.61, P < .001). At a median follow-up of 190 days (range, 67-476), 282 patients (39.2%) died. The STS and logistic EuroSCOREs were both higher in patients who died as compared to those in survivors (13.1 ± 6.2 vs.10.0 ± 5.8 and 43.4 ± 23.1 vs. 37.5 ± 22, respectively; P < .001). The observed and predicted 30-day mortality rates in the medical/BAV group were 10.1% observed, 12.3% by STS and 43.1% by logistic EuroSCORE. In the surgical AVR group, the rates were 12.8% observed, 8.4% by STS and 25.6% by logistic EuroSCORE. In the TAVI group, the rates were 11.7% observed, 11.8% by STS and 41.2% by logistic EuroSCORE. The odds ratio (OR) for 30-day mortality in the medical/BAV group was 1.05 (P = .01) with STS and 1.003 (P = .7) with logistic EuroSCORE. In the surgical AVR group, the OR was 1.09 (P = .07) with STS and 1.007 (P = .6) with logistic EuroSCORE. In the TAVI group, the OR was 1.14 (P = .03) with STS and 1.03 (P = .04) with logistic EuroSCORE. CONCLUSION In high-risk patients with severe aortic stenosis, STS score is superior to the logistic EuroSCORE in predicting mortality. Clinical judgment should play a major role in the selection of patients with severe aortic stenosis for the different therapeutic options.

Balloon aortic valvuloplasty for severe aortic stenosis as a bridge to transcatheter/surgical aortic valve replacement

Objectives: This study aimed to determine success‐ and complication rates after balloon aortic valvuloplasty (BAV) and the outcome of BAV as a standalone therapy versus BAV as a bridge to transcatheter/surgical aortic valve replacement (T/SAVR). Background: The introduction of transcatheter aortic valve replacement (TAVR) has led to a revival in BAV as treatment for patients with severe aortic stenosis. Methods: A cohort of 472 patients underwent 538 BAV procedures. The cohort was divided into two groups: BAV alone 387 (81.9%) and BAV as a bridge 85 (18.1%) to (n = 65, TAVR; n = 20, surgery). Clinical, hemodynamic, and follow‐up mortality data were collected. Results: There was no significant difference between the two groups in mean age (81.7 ± 8.3 vs. 83.2 ± 10.9 years, P = 0.18), society of thoracic surgeons score (13.1 ± 6.2 and 12.4 ± 6.4, P = 0.4), logistic EuroSCORE (45.4 ± 22.3 vs. 46.9 ± 21.8, P = 0.43), and other comorbidities. The mean increase in aortic valve area was 0.39 ± 0.25 in the BAV alone group and 0.42 ± 0.26 in the BAV as a bridge group, P = 0.33. The decrease in mean gradient was 24.1 ± 13.1 in the BAV alone group vs. 27.1 ± 13.8 in the BAV as a bridge group, P = 0.06. During a median follow up of 183 days [54–409], the mortality rate was 55.2% (n = 214) in the BAV alone group vs. 22.3% (n = 19) in the BAV as a bridge group during a median follow‐up of 378 days [177–690], P < 0.001. Conclusion: In high‐risk patients with aortic stenosis and temporary contraindications to SAVR/TAVR, BAV may be used as a bridge to intervention with good mid‐term outcomes.

A randomized, double-blind, placebo-controlled, multicenter, pilot study of the safety and feasibility of catheter-based intramyocardial injection of AdVEGF121 in patients with refractory advanced coronary artery disease

The experience with direct myocardial injection of adenovirus encoding angiogenic growth factor is limited to invasive surgical approach. Accordingly, we sought to evaluate, for the first time, in a randomized, double‐blind, placebo‐controlled, phase I pilot study the safety and feasibility of percutaneous catheter‐based intramyocardial delivery of a replication‐deficient adenovector encoding the 121‐amino‐acid isoform of vascular endothelial growth factor (AdVEGF121).

Prevalence and Effect of Myocardial Injury After Transcatheter Aortic Valve Replacement

The incidence and prognostic implication of myocardial injury after transcatheter aortic valve replacement (TAVR) have not been consistently studied. We aimed to assess the incidence and extent of myocardial injury after TAVR performed using transfemoral and transapical approaches. The clinical data from patients with aortic stenosis who underwent TAVR were retrospectively analyzed. The myocardial necrosis markers cardiac troponin I and creatine kinase (CK)-MB were assessed during hospitalization. Of the 150 TAVR patients, 95% and 50% had an abnormally elevated cardiac troponin I and CK-MB level, respectively. The transapical patients had significantly greater elevations of both cardiac troponin I (13.8 ± 14.0 vs 2.5 ± 5.8 ng/ml, p <0.001) and CK-MB (28.4 ± 24.2 vs 7.4 ± 8.6 ng/ml, p ≤0.001). On receiver operating curve analysis, postprocedural CK-MB (twofold increase) had high predictive power for 30-day mortality (area under the curve 0.85, p <0.001). Patients with high CK-MB levels had greater rates of postprocedural kidney injury (22% vs 6%, p = 0.026), in-hospital (22% vs 0%, p <0.001), 30-day (27% vs 1.5%, p <0.001), and 1-year mortality (41% vs 18%, p = 0.01). Baseline renal failure and no β-blocker treatment on admission were independent predictors of an elevated postprocedural CK-MB level. In conclusion, a cardiac biomarker increase after TAVR was common and more frequent among transapical access patients. A twofold increase (>7 ng/ml) in CK-MB after transfemoral TAVR was a surrogate for poor long-term outcomes.

Impact of Transapical Aortic Valve Replacement on Apical Wall Motion

BACKGROUND Recent reports indicate that the transapical approach for transcatheter aortic valve replacement may be associated with elevated cardiac enzymes, poor recovery of left ventricular function, and poor outcomes. The aim of this study was to evaluate whether transapical access is associated with apical dysfunction and to assess consequences on patient outcomes. METHODS In patients undergoing transapical aortic valve replacement, apical regional function was retrospectively assessed using the three standard echocardiographic long-axis views. Patients with abnormal baseline apical motion were excluded. Apical regional wall motion abnormality was assessed on preprocedural (baseline), immediate postprocedural (early [6 ± 2 days]), and late postprocedural (late [95 ± 76 days]) examinations. Apical regional wall motion abnormalities were categorized as normal, hypokinesis, or akinesis. RESULTS A total of 58 patients undergoing transapical aortic valve replacement were included in the present analysis. Of those, 16 (28%) developed early apical dysfunction. There were no differences in baseline characteristics between the patients who developed early apical dysfunction and those who did not. Patients who received 26-mm valves were more likely to develop apical dysfunction (40% vs. 69%, P = .05). In total, 50% of patients with apical dysfunction (eight of 16) had complete recovery of apical function but tended to have lower ejection fractions (50% vs. 60%, P = .045) at long-term follow-up. No difference in short-term or long-term mortality was detected in these small patient cohorts. CONCLUSIONS Myocardial injury during transapical access resulted in apical dysfunction early after the procedure in 28% of patients. This apical dysfunction was transient in half of the patients and was associated with a decrease in left ventricular function but did not affect mortality.

Outcomes of concomitant percutaneous coronary intervention and balloon aortic valvuloplasty

Background: Coronary artery disease often coexists with severe aortic stenosis. The feasibility and safety of combined balloon aortic valvuloplasty (BAV) and percutaneous coronary intervention (PCI) are unknown. Aim: To compare outcomes and complications of combined BAV and PCI with BAV alone. Methods: The study cohort consisted of 409 patients with severe aortic stenosis undergoing BAV from 1/2007 to 12/2010. Overall, 329 patients underwent BAV alone and 80 underwent concomitant PCI. Clinical and hemodynamic data, as well as acute and intermediate‐term outcomes, were collected. Results: At the operators discretion PCI was done before BAV in 66 (82.5%) and after in 14 (17.5%). Patients who underwent concomitant procedures had a higher incidence of prior stroke and a lower incidence of atrial fibrillation. Procedure time and fluoroscopic time were significantly greater in the BAV/PCI group, (90.0 ± 36.6 vs. 72.8 ± 39.8, P = 0.002 and 20.5 ± 10.9 vs. 12.9 ± 7.0, P < 0.001). Significantly more radiographic contrast was used in the BAV/PCI group (95.1 ± 45.5 vs. 36.7 ± 38.4 cm3, P < 0.001. Serious adverse events occurred with equal frequency 13.7 and 17.3%, P = 0.44). Transfusion requirement was also similar (21.2% vs. 20.0%, P = 0.81). The frequency of a periprocedural increase in troponin or creatinine was also similar. In the BAV alone group the mortality rate was 48.6% (n = 160) during a mean follow‐up of 191 days, and in the BAV/PCI group the mortality rate was 40% (n = 32) during mean follow‐up of 175.5 day, P = 0.34. Conclusion: Combined BAV and PCI are safe and are associated with similar complications as BAV alone and may offer protection against myocardial ischemia during BAV.