Mitral regurgitation increases systolic strains in remote zone and worsens left ventricular dyssynchrony in a swine model of ischemic cardiomyopathy.

Background: Ischemic mitral regurgitation (IMR) imposes volume overload on the left ventricle (LV), accelerating adverse LV remodeling. In this study, we sought to investigate the impact of volume overload due to IMR on regional myocardial contractile mechanics. Methods: Ten Yorkshire swine were induced with myocardial infarction (MI) by occluding the left circumflex coronary artery (LCx). Cardiac MRI was performed at baseline (BL) and 2.5 months (2.5M) post-MI. IMR was quantified with epicardial echocardiography 3 months post-MI. The animals were then assigned to 2 groups: no/mild MR (nmMR, n = 4) and moderate/severe MR (msMR, n = 6). MRI images were analyzed to assess infarction size, end-diastolic and end-systolic volume (EDV and ESV, respectively), ejection fraction (EF), longitudinal strain (LS), circumferential strain (CS), and systolic dyssynchrony index (SDI). The myocardial region was divided into infarction, border, and remote zones based on the LCx-supplied region. Results: There was no difference in the infarction size. Group-wise comparison of LS and CS between BL and 2.5M demonstrated that LS and CS in the infarction zone and the border zone decreased at 2.5M in both groups. However, LS and CS in the remote zone were elevated only in the msMR group (LS: -9.81 ± 3.96 vs. -12.58 ± 5.07, p < 0.01; CS; -12.78 ± 3.81 vs. -16.09 ± 3.33, p < 0.01) at 2.5M compared to BL. The SDI of CS was significantly elevated in the msMR group (0.1255 vs. 0.0974, p = 0.015) at 2.5M compared to BL. Conclusions: Elevated LS and CS in the remote zone were observed in moderate/severe MR and ventricular dyssynchrony. These elevated cardiac strains, coupled with ventricular dyssynchrony, may contribute to the progression of MR, thereby accelerating heart failure.

Transcatheter Myotomy to Reduce Left Ventricular Outflow Obstruction.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a source of morbidity in hypertrophic cardiomyopathy (HCM) and a life-threatening complication of transcatheter mitral valve replacement (TMVR) and transcatheter aortic valve replacement (TAVR). Available surgical and transcatheter approaches are limited by high surgical risk, unsuitable septal perforators, and heart block requiring permanent pacemakers. OBJECTIVES: The authors report the initial experience of a novel transcatheter electrosurgical procedure developed to mimic surgical myotomy. METHODS: We used septal scoring along midline endocardium (SESAME) to treat patients, on a compassionate basis, with symptomatic LVOT obstruction or to create space to facilitate TMVR or TAVR. RESULTS: In this single-center retrospective study between 2021 and 2023, 76 patients underwent SESAME. In total, 11 (14%) had classic HCM, and the remainder underwent SESAME to facilitate TMVR or TAVR. All had technically successful SESAME myocardial laceration. Measures to predict post-TMVR LVOT significantly improved (neo-LVOT 42 mm2 [Q1-Q3: 7-117 mm2] to 170 mm2 [Q1-Q3: 95-265 mm2]; P < 0.001; skirt-neo-LVOT 169 mm2 [Q1-Q3: 153-193 mm2] to 214 mm2 [Q1-Q3: 180-262 mm2]; P < 0.001). Among patients with HCM, SESAME significantly decreased invasive LVOT gradients (resting: 54 mm Hg [Q1-Q3: 40-70 mm Hg] to 29 mm Hg [Q1-Q3: 12-36 mm Hg]; P = 0.023; provoked 146 mm Hg [Q1-Q3: 100-180 mm Hg] to 85 mm Hg [Q1-Q3: 40-120 mm Hg]; P = 0.076). A total of 74 (97.4%) survived the procedure. Five experienced 3 of 76 (3.9%) iatrogenic ventricular septal defects that did not require repair and 3 of 76 (3.9%) ventricular free wall perforations. Neither occurred in patients treated for HCM. Permanent pacemakers were required in 4 of 76 (5.3%), including 2 after concomitant TAVR. Lacerations were stable and did not propagate after SESAME (remaining septum: 5.9 ± 3.3 mm to 6.1 ± 3.2 mm; P = 0.8). CONCLUSIONS: With further experience, SESAME may benefit patients requiring septal reduction therapy for obstructive hypertrophic cardiomyopathy as well as those with LVOT obstruction after heart valve replacement, and/or can help facilitate transcatheter valve implantation.

Prospective validation of a risk score to predict pacemaker implantation after transcatheter aortic valve replacement.

INTRODUCTION: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre-existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score. METHODS: We prospectively evaluated all patients without pre-existing pacemakers, ICD, or pre-existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision-making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis. RESULTS: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05-3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74-0.88], p < 0.001). CONCLUSIONS: The ERS prospectively predicted the need for PPM in a serial, real-world cohort of patients undergoing TAVR with a balloon-expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR.

Hybrid Closure of Postinfarction Apical Ventricular Septal Defect Using Septal Occluder Device and Right Ventricular Free Wall: The Apical BASSINET Concept.

BACKGROUND: Postinfarction ventricular septal defect (VSD) is a catastrophic complication of myocardial infarction. Surgical repair still has poor outcomes. This report describes clinical outcomes after a novel hybrid transcatheter/surgical repair in patients with apical VSD. METHODS: Seven patients with postmyocardial infarction apical VSD underwent hybrid transcatheter repair via subxiphoid surgical access. A transcatheter occluder (Amplatzer Septal Occluder) with a trailing premounted suture was deployed through the right ventricular wall and through the ventricular septum into the left ventricular apex. The trailing suture was used to connect an anchor external to the right ventricular wall. Tension on the suture then collapses the right ventricular free wall against the septum and left ventricular occluder, thereby obliterating the VSD. Outcomes were compared with 9 patients who underwent surgical repair using either patch or primary suture closure. RESULTS: All patients had significant left-to-right shunt (Qp:Qs 2.5:1; interquartile range [IQR, 2.1-2.6] hybrid repair versus 2.0:1 [IQR, 2.0-2.5] surgical repair), and elevated right ventricular systolic pressure (62 [IQR, 46-71] versus 49 [IQR, 43-54] mm Hg, respectively). All had severely depressed stroke volume index (22 versus 21 mL/m2) with ≈45% in each group requiring mechanical support preprocedurally. The procedure was done 15 (IQR, 10-50) versus 24 (IQR, 10-134) days postmyocardial infarction, respectively. Both groups of patients underwent repair with technical success and without intraprocedural death. One patient in the hybrid group and 4 in the surgical group developed multiorgan failure. The hybrid group had a higher survival at discharge (86% versus 56%) and at 30 days (71% versus 56%), but similar at 1 year (57% versus 56%). During follow-up, 1 patient in each group required reintervention for residual VSD (hybrid: 9 months versus surgical: 5 days). CONCLUSIONS: Early intervention with a hybrid transcatheter/surgical repair may be a viable alternative to traditional surgery for postinfarction apical VSD.

Trends in surgical aortic valve replacement in pre- and post-transcatheter aortic valve replacement eras at a structural heart center.

Background: The advent of transcatheter aortic valve replacement (TAVR) has directly impacted the lifelong management of patients with aortic valve disease. The U.S. Food and Drug Administration has approved TAVR for all surgical risk: prohibitive (2011), high (2012), intermediate (2016), and low (2019). Since then, TAVR volumes are increasing and surgical aortic valve replacements (SAVR) are decreasing. This study sought to evaluate trends in isolated SAVR in the pre- and post-TAVR eras. Methods: From January 2000 to June 2020, 3,861 isolated SAVRs were performed at a single academic quaternary care institution which participated in the early trials of TAVR beginning in 2007. A formal structural heart center was established in 2012 when TAVR became commercially available. Patients were divided into the pre-TAVR era (2000-2011, n = 2,426) and post-TAVR era (2012-2020, n = 1,435). Data from the institutional Society of Thoracic Surgeons National Database was analyzed. Results: The median age was 66 years, similar between groups. The post-TAVR group had a statistically higher rate of diabetes, hypertension, dyslipidemia, heart failure, more reoperative SAVR, and lower STS Predicted Risk of Mortality (PROM) (2.0% vs. 2.5%, p < 0.0001). There were more urgent/emergent/salvage SAVRs (38% vs. 24%) and fewer elective SAVRs (63% vs. 76%), (p < 0.0001) in the post-TAVR group. More bioprosthetic valves were implanted in the post-TAVR group (85% vs. 74%, p < 0.0001). Larger aortic valves were implanted (25 vs. 23 mm, p < 0.0001) and more annular enlargements were performed (5.9% vs. 1.6%, p < 0.0001) in the post-TAVR era. Postoperatively, the post-TAVR group had less blood product transfusion (49% vs. 58%, p < 0.0001), renal failure (1.4% vs. 4.3%, p < 0.0001), pneumonia (2.3% vs. 3.8%, p = 0.01), shorter lengths of stay, and lower in-hospital mortality (1.5% vs. 3.3%, p = 0.0007). Conclusion: The approval of TAVR changed the landscape of aortic valve disease management. At a quaternary academic cardiac surgery center with a well-established structural heart program, patients undergoing isolated SAVR in the post-TAVR era had lower STS PROM, more implantation of bioprosthetic valves, utilization of larger valves, annular enlargement, and lower in-hospital mortality. Isolated SAVR continues to be performed in the TAVR era with excellent outcomes. SAVR remains an essential tool in the lifetime management of aortic valve disease.

Neutrophil-to-Lymphocyte Ratios in Patients Undergoing Aortic Valve Replacement: The PARTNER Trials and Registries.

Background The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow-up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5-24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70-4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18-1.63; P<0.0001) compared with those with low NLR, irrespective of treatment modality. In both patients treated with TAVR and patients treated with SAVR, NLR decreased between baseline and 2 years. A 1-unit observed decrease in NLR between baseline and 1 year was associated with lower risk of death or rehospitalization between 1 year and 3 years (aHR, 0.86; 95% CI, 0.82-0.89; P<0.0001). Conclusions Elevated baseline NLR was independently associated with increased subsequent mortality and rehospitalization after TAVR or SAVR. The observed decrease in NLR after TAVR or SAVR was associated with improved outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00530894, NCT0134313, NCT02184442, NCT03225001, NCT0322141.

Transcatheter Myotomy to Relieve Left Ventricular Outflow Tract Obstruction: The Septal Scoring Along the Midline Endocardium Procedure in Animals.

BACKGROUND: Left ventricular outflow tract obstruction complicates hypertrophic cardiomyopathy and transcatheter mitral valve replacement. Septal reduction therapies including surgical myectomy and alcohol septal ablation are limited by surgical morbidity or coronary anatomy and high pacemaker rates, respectively. We developed a novel transcatheter procedure, mimicking surgical myotomy, called Septal Scoring Along the Midline Endocardium (SESAME). METHODS: SESAME was performed in 5 naive pigs and 5 pigs with percutaneous aortic banding-induced left ventricular hypertrophy. Fluoroscopy and intracardiac echocardiography guided the procedures. Coronary guiding catheters and guidewires were used to mechanically enter the basal interventricular septum. Imparting a tip bend to the guidewire enabled intramyocardial navigation with multiple df. The guidewire trajectory determined the geometry of SESAME myotomy. The myocardium was lacerated using transcatheter electrosurgery. Cardiac function and tissue characteristics were assessed by cardiac magnetic resonance at baseline, postprocedure, and at 7- or 30-day follow-up. RESULTS: SESAME myotomy along the intended trajectory was achieved in all animals. The myocardium splayed after laceration, increasing left ventricular outflow tract area (753 to 854 mm2, P=0.008). Two naive pigs developed ventricular septal defects due to excessively deep lacerations in thin baseline septa. No hypertrophy model pig, with increased septal thickness and left ventricular mass compared with naive pigs, developed ventricular septal defects. One animal developed left axis deviation on ECG but no higher conduction block was seen in any animal. Coronary artery branches were intact on angiography with no infarction on cardiac magnetic resonance late gadolinium imaging. Cardiac magnetic resonance chamber volumes, function, flow, and global strain were preserved. No myocardial edema was evident on cardiac magnetic resonance T1 mapping. CONCLUSIONS: This preclinical study demonstrated feasibility of SESAME, a novel transcatheter myotomy to relieve left ventricular outflow tract obstruction. This percutaneous procedure using available devices, with a safe surgical precedent, is readily translatable into patients.

The PARTNER 3 Bicuspid Registry for Transcatheter Aortic Valve Replacement in Low-Surgical-Risk Patients.

OBJECTIVES: The study compared 1-year outcomes between transcatheter aortic valve replacement (TAVR) patients with bicuspid aortic valve (BAV) morphology and clinically similar patients having tricuspid aortic valve (TAV) morphology. BACKGROUND: There are limited prospective data on TAVR using the SAPIEN 3 device in low-surgical-risk patients with severe, symptomatic aortic stenosis and bicuspid anatomy. METHODS: Low-risk, severe aortic stenosis patients with BAV were candidates for the PARTNER 3 (Placement of Aortic Transcatheter Valves 3) (P3) bicuspid registry or the P3 bicuspid continued access protocol. Patients treated in these registries were pooled and propensity score matched to TAV patients from the P3 randomized TAVR trial. Outcomes were compared between groups. The primary endpoint was the 1-year composite rate of death, stroke, and cardiovascular rehospitalization. RESULTS: Of 320 total submitted BAV patients, 169 (53%) were treated, and most were Sievers type 1. The remaining 151 patients were excluded caused by anatomic or clinical criteria. Propensity score matching with the P3 TAVR cohort (496 patients) yielded 148 pairs. There were no differences in baseline clinical characteristics; however, BAV patients had larger annuli and they experienced longer procedure duration. There was no difference in the primary endpoint between BAV and TAV (10.9% vs 10.2%; P = 0.80) or in the rates of the individual components (death: 0.7% vs 1.4%; P = 0.58; stroke: 2.1% vs 2.0%; P = 0.99; cardiovascular rehospitalization: 9.6% vs 9.5%; P = 0.96). CONCLUSIONS: Among highly select bicuspid aortic stenosis low-surgical-risk patients without extensive raphe or subannular calcification, TAVR with the SAPIEN 3 valve demonstrated similar outcomes to a matched cohort of patients with tricuspid aortic stenosis.

Ventricular reshaping with a beating heart implant improves pump function in experimental heart failure.

OBJECTIVE: The left ventricle remodels from an ellipsoidal/conical shape to a spherical shape after a myocardial infarction. The spherical ventricle is inefficient as a pumping chamber, has higher wall stresses, and can lead to congestive heart failure. We sought to investigate if restoring physiological ventricular shape with a beating heart implant improves pump function. METHODS: Rats were induced with a myocardial infarction, developing left ventricular dilatation and dysfunction, and becoming spherical over 3 weeks. Thereafter, they were randomized to undergo left ventricular reshaping with a beating heart implant (n = 19) or continue follow-up without an implant (n = 19). Biweekly echocardiography was performed until 12 weeks, with half the rats euthanized at 6 weeks and remaining at 12 weeks. At termination, invasive hemodynamic parameters and histopathology were performed. RESULTS: At 3 weeks after the infarction, rats had a 22% fall in ejection fraction, 31% rise in end diastolic volume, and 23% rise in sphericity. Transventricular implant reshaping reduced the volume by 12.6% and sphericity by 21%, restoring physiologic ventricular shape and wall stress. Over the 12-week follow-up, pump function improved significantly with better ventricular-vascular coupling in the reshaped hearts. In this group, cardiomyocyte cross-section area was higher and the cells were less elongated. CONCLUSIONS: Reshaping a postinfarction, failing left ventricle to restore its physiological conical shape significantly improves long-term pump function.

Undersizing mitral annuloplasty alters left ventricular mechanics in a swine model of ischemic mitral regurgitation.

OBJECTIVE: Undersizing mitral annuloplasty (UMA) is a frequently used surgical repair technique to correct ischemic mitral regurgitation in patients with heart failure. In this study, we sought to test the hypothesis that downsizing the mitral annulus can adversely affect the shape and mechanics of the left ventricle inhibiting its functional recovery. METHODS: Eighteen farm swine that underwent an inferolateral myocardial infarction and developed ischemic mitral regurgitation of >2+ severity after 2 months were assigned as follows: 9 swine received an undersized mitral annuloplasty, 6 received papillary muscle approximation (PMA), and 3 animals did not receive any other intervention. Animals lived another 3 months and cardiac magnetic resonance imaging was performed before termination to assess ventricle mechanics and function. RESULTS: Ejection fraction was comparable between the 2 repair groups before surgery, but was significantly lower in UMA at 38.89% ± 7.91% versus 50.83% ± 9.04% in the PMA group (P = .0397). Animals receiving UMA had lower regional peak fractional shortening and reduced systolic and diastolic radial velocities compared with PMA and in some regions were lower than sham. Animals that underwent UMA had higher circumferential strain than sham, but lower than PMA. UMA animals have lower longitudinal strain compared to sham group and lower LV torsion than PMA. CONCLUSIONS: Undersizing the mitral annulus with an annuloplasty ring can restore valvular competence, but unphysiologically impair ventricle mechanics. Mitral valve repair strategies should focus not only on restoring valve competence, but preserving ventricle mechanics.

Early outcomes of transcatheter mitral valve replacement with the Tendyne system in severe mitral annular calcification.

BACKGROUND: Treatment of mitral regurgitation (MR) associated with severe mitral annular calcification (MAC) is challenging due to the high risk of fatal atrioventricular groove disruption and significant paravalvular leak. AIMS: The aim of this study was to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) with the Tendyne valve (Abbott Structural) in patients with MR and MAC. METHODS: Twenty patients (mean age 78 years; 11 women) who were treated with the Tendyne valve, either compassionate use (CU; closed) or as part of The Feasibility Study of Tendyne in MAC (NCT03539458), had reported outcomes in a median follow-up duration of 368 days. RESULTS: In all patients, a valve was implanted with no procedural mortality and successful hospital discharge. Two embolic events occurred, including one with mesenteric ischaemia and one non-disabling stroke. At 30 days and one year, all-cause mortality occurred in one (5%) and eight patients (40%), respectively. At one year, six patients had been hospitalised for heart failure (30%). There was no prosthetic dysfunction, and MR remained absent in all patients at one year. Clinical improvement, measured by New York Heart Association Functional Class, occurred in 11 of 12 patients who were alive at one year. Among seven survivors with Kansas City Cardiomyopathy Questionnaire (KCCQ) data, mean increase in KCCQ score was 29.9±26.3 at one year with improvement of ≥10 points in five (71.4%) patients. CONCLUSIONS: In patients with MR and severe MAC, TMVR with the Tendyne valve was associated with encouraging acute outcomes, midterm durability, and clinical improvement. Dedicated TMVR therapy may have a future role in these anatomically challenging, high-risk patients.

Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement: PARTNER 3 Trial.

OBJECTIVES: The aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). BACKGROUND: There is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR. METHODS: In the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter. RESULTS: Among 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality. CONCLUSIONS: In the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.