Leadless pacemaker with transcatheter aortic valve implantation: A single-center experience.

BACKGROUND: The safety and efficacy of leadless pacemakers (LP) in transcatheter aortic valve implant (TAVI) patients is not well known due to paucity of data. Herein, we compared outcomes between leadless pacemakers to traditional dual chamber pacemakers (DCP) following TAVI. METHODS: A single-center retrospective study was conducted, including a total of 27 patients with LP and 33 patients with DCP after TAVI between November 2013 and May 2021. We compared baseline demographics, pacemaker indications, complication rates, percent pacing, and ejection fractions. RESULTS: Leading indications for pacemaker implant were complete heart block (74% LP, 73% DCP) and high degree atrioventricular block (26% LP, 21% DCP). Twenty-two (82%) LP patients had devices implanted in the right ventricular septal-apex. Three (9%) DCP patients required rehospitalization for pocket related complications. Zero pacemaker-related mortality was observed in both groups. Frequency of ventricular pacing and ejection fraction was similar between LP and DCP groups. CONCLUSION: From this single-center retrospective study, LP implant was feasible following TAVI and was found to have comparable performance to DCPs. LPs may be a reasonable alternative in TAVI patients where single ventricular pacing is indicated. Larger studies are required to validate these findings.

Hemodynamic outcomes after valve-in-valve transcatheter aortic valve replacement: a single-center experience.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a safe, effective alternative to redo aortic valve surgery in high-risk patients with degenerated surgical bioprosthetic valves. However, ViV-TAVR has been associated high postprocedural valvular gradients, compared with TAVR for native-valve aortic stenosis. METHODS: We performed a retrospective study of all patients who underwent ViV-TAVR for a degenerated aortic valve bioprosthesis between January 1, 2013 and March 31, 2019 at our center. The primary outcome was postprocedural mean aortic valve gradient. Outcomes were compared across surgical valve type (stented versus stentless), surgical valve internal diameter (≤19 versus >19 mm), and transcatheter aortic valve type (self-expanding vs. balloon-expandable). RESULTS: Overall, 89 patients underwent ViV-TAVR. Mean age was 69.0±12.6 years, 61% were male, and median Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.4 [interquartile range, 3.2-8.5]. Bioprosthesis mode of failure was stenotic (58% of patients), regurgitant (24%), or mixed (18%). The surgical valve was stented in 75% of patients and stentless in 25%. The surgical valve's internal diameter was ≤19 mm in 45% of cases. A balloon-expandable transcatheter valve was used in 53% of procedures. Baseline aortic valve area and mean gradients were 0.87±0.31 cm2 and 36±18 mmHg, respectively. These improved after ViV-TAVR to 1.38±0.55 cm2 and 18±11 mmHg at a median outpatient follow-up of 331 [67-394] days. Higher postprocedural mean gradients were associated with surgical valves having an internal diameter ≤19 mm (24±13 versus 16±8, P=0.002) and with stented surgical valves (22±11 versus 12±6, P<0.001). CONCLUSIONS: ViV-TAVR is an effective option for treating degenerated surgical aortic bioprostheses, with acceptable hemodynamic outcomes. Small surgical valves and stented surgical valves are associated with higher postprocedural gradients.

Transcatheter valve-in-valve implantation for degenerated stentless aortic bioroots.

BACKGROUND: Open surgical repair of a failed valve-sparing aortic root replacement (VSARR) or stentless bioroot aortic root replacement (bio-ARR) entails significant operative risks. Whether valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) is feasible in patients with a previous VSARR or stentless bio-ARR remains unclear, given lingering concerns about the ill-defined aortic annulus in these patients and the potential for coronary obstruction. We present our experience with patients who had a previous VSARR or stentless bio-ARR and underwent ViV-TAVR to repair a degenerated aortic valve with combined valvular disease, aortic insufficiency and aortic stenosis. METHODS: In this retrospective data review, we identified and analyzed consecutive patients with a previous VSARR or stentless bio-ARR who underwent ViV-TAVR between December 1, 2014 and August 31, 2019. RESULTS: ViV-TAVR was performed in twelve high-risk patients with previous VSARR or bio-ARR during the study period. Of these, seven received Medtronic Freestyle porcine stentless bioprosthetic aortic roots, three received homograft aortic roots, one underwent a Ross procedure and one underwent VSARR. ViV-TAVR restored satisfactory valve function in all patients, and technical success was 100%. No patient had more than mild regurgitation after implantation. No thirty-day mortality was seen. One patient had major bleeding after transapical access, one patient had a transient ischemic stroke, and one patient needed permanent pacemaker implantation. At a median last follow-up of 21.5 months (interquartile range, 9.0-69.0 months), all patients remained alive and had satisfactory valve function. CONCLUSIONS: In this study, ViV-TAVR was a clinically effective option for treating patients with a failed stentless bio-ARR or previous VSARR. Short-term and intermediate-term results after these procedures were favorable. These findings may have important implications for treating high-risk patients with structural aortic root deterioration and call for better transcatheter heart valves that are suitable for treating aortic insufficiency.

Transcatheter aortic valve replacement after chest radiation: A propensity-matched analysis.

BACKGROUND: Chest radiation therapy (CRT) for malignant thoracic neoplasms is associated with development of valvular heart disease years later. As previous radiation exposure can complicate surgical treatment, transcatheter aortic valve replacement (TAVR) has emerged as an alternative. However, outcomes data are lacking for TAVR patients with a history of CRT. METHODS: We conducted a retrospective study of all patients who underwent a TAVR procedure at a single institution between September 2012 and November 2018. Among 1341 total patients, 50 had previous CRT. These were propensity-matched in a 1:2 ratio to 100 patients without history of CRT. Thirty-day adverse events were analyzed with generalized estimating equation models. Overall mortality was analyzed with stratified Cox regression modelling. RESULTS: Median clinical follow-up was 24 months (interquartile range [IQR], 12-44 months). There was no difference between CRT and non-CRT patients in overall mortality (hazard ratio [HR] 0.84 [0.37-1.90], P = 0.67), 30-day mortality (HR 3.1 [0.49-20.03], P = 0.23), or 30-day readmission rate (HR 1.0 [0.43-2.31], P = 1). There were no differences in the rates of most adverse events, but patients with CRT history had higher rates of postprocedural respiratory failure (HR 3.63 [1.32-10.02], P = 0.01) and permanent pacemaker implantation (HR 2.84 [1.15-7.01], P = 0.02). CONCLUSIONS: For patients with aortic valve stenosis and previous CRT, TAVR is safe and effective, with outcomes similar to those in the general aortic stenosis population. Patients with history of CRT are more likely to have postprocedural respiratory failure and to require permanent pacemaker implantation.

Minimally Invasive Direct Access Balloon-Expandable Transcatheter Mitral Valve Replacement for Extensive Mitral Annular Calcification after Transcatheter Aortic Valve Replacement.

Mitral annular calcification can pose a formidable surgical challenge in the setting of mitral valve replacement for mitral stenosis. Although there are reports of transapical valve-in-valve transcatheter mitral valve replacement in the setting of degenerated bioprosthetic mitral valve replacement, there is less experience with transcatheter mitral valve replacement for mitral annular calcification. This report describes a patient who previously received a transcatheter aortic valve replacement and then subsequently underwent a minimally invasive right thoracotomy for transcatheter mitral valve replacement with a successful result. We discuss technical pearls and operative considerations based on an extensive experience with minimally invasive valve surgery from a right mini-thoracotomy.

Percutaneous Closure of 2 Paravalvular Leaks and a Gerbode Defect after Mitral Valve Replacement for Infective Endocarditis.

Surgical valve replacement after infective endocarditis can result in local destructive paravalvular lesions. A 30-year-old woman with infective endocarditis underwent mitral valve replacement that was complicated postoperatively by 2 paravalvular leaks. During percutaneous closure of the leaks, a Gerbode defect was also found and closed. We discuss our patient's case and its relation to others in the relevant medical literature. To our knowledge, we are the first to describe the use of a percutaneous approach to close concomitant paravalvular leaks and a Gerbode defect.

Outcomes of hemodynamic support with Impella in very high-risk patients undergoing balloon aortic valvuloplasty: Results from the Global cVAD Registry.

BACKGROUND: Reports on the role of hemodynamic support devices in patients with severe aortic stenosis (AS) and left ventricular (LV) dysfunction undergoing balloon aortic valvuloplasty (BAV) are limited. METHODS: Patients were identified from the cVAD registry, an ongoing multicenter voluntary registry at selected sites in North America that have used Impella in >10 patients. RESULTS: A total of 116 patients with AS who underwent BAV with Impella support were identified. Mean age was 80.41±9.03years and most patients were male. Mean STS score was 18.77%±18.32, LVEF was 27.14%±16.07, and 42% underwent concomitant PCI. In most cases Impella was placed electively prior to BAV, whereas 26.7% were placed as an emergency. The two groups had similar baseline characteristics except for higher prevalence of CAD and lower LVEF in the elective group, and higher STS score in the emergency group. Elective strategy was associated higher 1-year survival compared to emergency placement (56% vs. 29.2%, p=0.003). One-year survival was higher when BAV was used as a bridge to definitive therapy as opposed to palliative treatment (90% vs. 28%, p<0.001). On multivariate analysis, STS score and aim of BAV (bridge to definitive therapy vs. palliative indication) were independent predictors of mortality. CONCLUSION: In this large cohort of patients with AS and severe LV dysfunction undergoing BAV, our results demonstrates feasibility and promising long-term outcomes using elective Impella support with the intention to bridge to a definitive therapy.

A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Nonischemic Heart Failure.

RATIONALE: Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and nonischemic heart failure (HF). OBJECTIVE: To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial. METHODS AND RESULTS: We sequentially allocated 60 patients to a dosing cohort (20 per dose group) and randomized them to transendocardial MPC injections (n=15) or mock procedures (n=5). The primary objective was safety, including antibody testing. Secondary efficacy end points included major adverse cardiac events (MACE; cardiac death, myocardial infarction, or revascularization), left ventricular imaging, and other clinical-event surrogates. Safety and MACE were evaluated for up to 3 years. MPC injections were feasible and safe. Adverse events were similar across groups. No clinically symptomatic immune responses were noted. MACE was seen in 15 patients: 10 of 45 (22%) MPC-treated and 5 of 15 (33%) control patients. We found no differences between MPC-treated and control patients in survival probability, MACE-free probability, and all-cause mortality. We conducted a post hoc analysis of HF-related MACE (HF hospitalization, successfully resuscitated cardiac death, or cardiac death) and events were significantly reduced in the 150 million MPC group (0/15) versus control (5/15; 33%), 25 million MPC group (3/15; 20%), and 75 million MPC group (6/15; 40%); the 150 million MPC group differed significantly from all groups according to Kaplan-Meier statistics >3 years (P=0.025 for 150 million MPC group versus control). CONCLUSIONS: Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients. High-dose allogeneic MPCs may provide benefits in this population.

Comparison of scanning electron microscopy and optical coherence tomography for imaging of coronary bifurcation stents.

BACKGROUND: Optical coherence tomography (OCT) is a new intracoronary imaging modality that has excellent resolution and image quality and has been used to image neointimal coverage after stent implantation. OCT has been compared to histologic, intravascular ultrasound, and scanning electron microscopy (SEM) studies. However, OCT has not been compared with SEM for imaging stent coverage over side branches. OBJECTIVE: The aim of this study was to compare OCT with SEM in imaging neointimal coverage over stent struts bridging coronary side-branch ostia. METHODS: Using a balloon-overstretch in-stent restenosis model, we deployed 38 everolimus-eluting stents across coronary bifurcations in nine pigs. We performed OCT immediately after stenting and 4 weeks later; SEM was performed after euthanizing the pigs. OCT images of each stent were compared to the corresponding SEM image. RESULTS: We analyzed OCT frames (n=111) for strut-level neointimal coverage and compared them to corresponding SEM images. The concordance correlation coefficient was 0.809 (95%CI; 0.734-0.864) and 0.951 (95%CI; 0.930-0.966) for covered and uncovered struts, respectively. CONCLUSIONS: In a non-atherosclerotic pig model, we showed strong agreement between OCT and SEM in imaging coverage of stent struts bridging side-branch ostia.

Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial.

AIMS: Adipose-derived regenerative cells (ADRCs) can be isolated from liposuction aspirates and prepared as fresh cells for immediate administration in cell therapy. We performed the first randomized, placebo-controlled, double-blind trial to examine the safety and feasibility of the transendocardial injections of ADRCs in no-option patients with ischemic cardiomyopathy. METHODS AND RESULTS: Procedural, postoperative, and follow-up safety end points were monitored up to 36 months. After baseline measurements, efficacy was assessed by echocardiography and single-photon emission computed tomography (6, 12, and 18 months), metabolic equivalents and maximal oxygen consumption (MVO2) (6 and 18 months), and cardiac magnetic resonance imaging (6 months). We enrolled 21 ADRC-treated and 6 control patients. Liposuction was well tolerated, ADRCs were successfully prepared, and transendocardial injections were feasible in all patients. No malignant arrhythmias were seen. Adverse events were similar between groups. Metabolic equivalents and MVO2 values were preserved over time in ADRC-treated patients but declined significantly in the control group. The difference in the change in MVO2 from baseline to 6 and 18 months was significantly better in ADRC-treated patients compared with controls. The ADRC-treated patients showed significant improvements in total left ventricular mass by magnetic resonance imaging and wall motion score index. Single-photon emission computed tomography results suggested a reduction in inducible ischemia in ADRC-treated patients up to 18 months. CONCLUSION: Isolation and transendocardial injection of autologous ADRCs in no-option patients were safe and feasible. Our results suggest that ADRCs may preserve ventricular function, myocardial perfusion, and exercise capacity in these patients.

Safety and feasibility of mapping and stem cell delivery in the presence of an implanted left ventricular assist device: a preclinical investigation in sheep.

The objective of this study was to determine the safety and feasibility of performing transendocardial electromechanical mapping and mesenchymal precursor stem cell injections after left ventricular assist device (LVAD) implantation in a sheep model of acute myocardial infarction. Six sheep were assigned to either an acute or chronic group. Then we created an acute myocardial infarction in each by occluding the distal left anterior descending coronary artery with a balloon for 90 minutes. All the sheep underwent LVAD implantation 30 days later. On the same day, sheep in the acute group underwent transendocardial cell injections and were euthanized. Sheep in the chronic group received cell injections 2 weeks after LVAD implantation and were euthanized 30 days later. The presence of the LVAD or the use of chest-closure wires did not interfere with electromechanical mapping. Furthermore, no adverse events were observed during electromechanical mapping or the stem cell injections. In all sheep, the LVAD flow rate was approximately 4 L/min during mapping and the injections, and no adjustments were required. Histologic analysis confirmed that the mesenchymal precursor stem cells were successfully delivered. No differences were observed between the acute and chronic groups. In conclusion, our study showed that transendocardial electromechanical mapping and stem cell injections are safe and feasible in the presence of an LVAD. Surgically implanted metal devices, including the LVAD, steel chest-closure wire, and skin staples, were compatible with the electromechanical mapping system.

Xenotransplantation of human unrestricted somatic stem cells in a pig model of acute myocardial infarction.

BACKGROUND: Stem cell therapy may help restore cardiac function after acute myocardial infarction (AMI), but the optimal therapeutic cell type has not been identified. METHODS: We examined the effects of CD34-/CD45- human unrestricted somatic stem cells (USSCs) in pigs (n = 30) with an AMI created by a 90-min occlusion of the left anterior descending coronary artery. Pigs were randomly assigned to receive either USSCs (302 ± 23 × 10(6) cells) or phosphate-buffered saline via 15 NOGA-guided transendocardial injections 10 days after AMI. Cyclosporine A (10 mg/kg orally, twice a day) was started in all pigs 3 days before control or cell treatment. Cardiac function was assessed by echocardiography before injection and at 4 and 8 weeks after treatment. Serum titers for pig IgG antibodies against USSCs were also measured at these time points and before AMI. RESULTS: Compared with control pigs, USSC-treated pigs showed no significant differences in any of the functional parameters examined. USSC-treated pigs showed variable increases in anti-USSC IgG antibody titers in the blood and chronic inflammatory infiltrates at the cell injection sites. Immunohistochemical studies of the injection sites using human anti-mitochondrial antibodies failed to detect implanted USSCs. CONCLUSIONS: We conclude that human USSCs did not improve cardiac function in a pig model of AMI. Cell transplantation in a xenogeneic setting may obscure the benefits of stem cell therapy.

Restoration of microcirculatory patency after myocardial infarction: results of current coronary interventional strategies and techniques.

We sought to evaluate the restoration of microcirculatory patency after primary percutaneous coronary intervention (PCI) in an unselected cohort of patients at a tertiary center.We retrospectively evaluated distributions of the Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG) and the myocardial blush grade (MBG) in all primary PCI procedures performed at our institution during 2008. We defined optimal microvascular perfusion as simultaneous TMPG 3 and MBG 3 at procedure's end.Ninety-nine patients (mean age, 61.5 ± 12.7 yr; 64 men) underwent primary PCI. Microvascular perfusion was optimal in 69 patients (69.7%) and was associated with lower peaks of enzymes than those occurring in patients with suboptimal perfusion. When optimal microvascular perfusion was achieved, early spontaneous recanalization was more frequently observed, as expressed by a higher frequency of TIMI-3 flow (34.8% vs 10%; P=0.006), TMPG 3 (26% vs 3.3%; P=0.004), and MBG 3 (24.6% vs 3.3%; P=0.004) on the initial angiogram before primary PCI. A higher frequency of MBG 3 (50% vs 20%; P=0.005) was seen after initial recanalization in patients with optimal microvascular perfusion. Multiple regression analysis showed that MBG after initial recanalization and the use of drug-eluting stents were associated with optimal perfusion.Despite successful recanalization of the culprit coronary artery, optimal microvascular perfusion was achieved in less than 75% of the patients. Restoration of the microvasculature was associated with smaller infarcts. Procedure-related variables associated with suboptimal perfusion were unlikely to be causative.

Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial.

CONTEXT: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. OBJECTIVE: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. DESIGN, SETTING, AND PATIENTS: A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. INTERVENTION: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). MAIN OUTCOME MEASURES: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. RESULTS: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. CONCLUSION: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00824005.