Changes in Right Ventricular-to-Pulmonary Artery Coupling After Transcatheter Edge-to-Edge Repair in Secondary Mitral Regurgitation.

BACKGROUND: Preprocedural right ventricular-to-pulmonary artery (RV-PA) coupling is a major predictor of outcome in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). However, clinical significance of changes in RV-PA coupling after M-TEER is unknown. OBJECTIVES: The aim of this study was to evaluate changes in RV-PA coupling after M-TEER, their prognostic value, and predictors of improvement. METHODS: This was a retrospective observational study, including patients undergoing successful M-TEER (residual mitral regurgitation ≤2+ at discharge) for SMR at 13 European centers and with complete echocardiographic data at baseline and short-term follow-up (30-180 days). RV-PA coupling was assessed with the use of echocardiography as the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). All-cause death was assessed at the longest available follow-up starting from the time of the echocardiographic reassessment. RESULTS: Among 501 patients included, 331 (66%) improved their TAPSE/PASP after M-TEER (responders) at short-term follow-up (median: 89 days; IQR: 43-159 days), whereas 170 (34%) did not (nonresponders). Lack of previous cardiac surgery, low postprocedural mitral mean gradient, low baseline TAPSE, high baseline PASP, and baseline tricuspid regurgitation were independently associated with TAPSE/PASP improvement after M-TEER. Compared with nonresponders, responders had lower New York Heart Association functional class and less heart failure hospitalizations at short-term follow-up. Improvement in TAPSE/PASP was independently associated with reduced risk of mortality at long-term follow-up (584 days; IQR: 191-1,243 days) (HR: 0.65 [95% CI: 0.42-0.92]; P = 0.017). CONCLUSIONS: In patients with SMR, improvement in TAPSE/PASP after successful M-TEER is predicted by baseline clinical and echocardiographic variables and postprocedural mitral gradient, and is associated with a better outcome.

Temporal trend and potential impact of angiotensin receptor neprilysin inhibitors on transcatheter edge-to-edge mitral valve repair.

INTRODUCTION AND OBJECTIVES: Transcatheter edge-to-edge repair (TEER) should be considered in patients with heart failure and secondary mitral regurgitation (MR). Angiotensin receptor-neprilysin inhibitors (ARNIs) have been demonstrated to improve prognosis in heart failure. We aimed to evaluate the impact ARNIs on patient selection and outcomes. METHODS: The population of the Spanish TEER prospective registry (March 2012 to January 2021) was divided into 2 groups: a) TEER before the ARNI era (n=450) and b) TEER after the recommendation of ARNIs by European Guidelines (n=639), with further analysis according to intake (n=52) or not (n=587) of ARNIs. RESULTS: A total of 1089 consecutive patients underwent TEER for secondary MR. In the ARNI era, there was a reduction in left ventricle dilation (82mL vs 100mL, P=.025), and better function (35% vs 38%, P=.011). At 2 years of follow-up, mortality (10.6% vs 17.3%, P <.001) and heart failure readmissions (16.6% vs 27.8%, P <.001) were lower in the ARNI era, but not recurrent MR. In the ARNI era, 1- and 2-year mortality were similar irrespective of ARNI intake but patients on ARNIs had a lower risk of readmission+mortality at 2 years (OR, 0.369; 95%CI, 0.137-0.992; P=.048), better NYHA class, and lower recurrence of MR III-IV (1.9% vs 14.3%, P=.011). CONCLUSIONS: Better patient selection for TEER has been achieved in the last few years with a parallel improvement in outcomes. The use of ARNIs was associated with a significant reduction in overall events, better NYHA class, and lower MR recurrence.

Coronary Microcirculation Downstream Non-Infarct-Related Arteries in the Subacute Phase of Myocardial Infarction: Implications for Physiology-Guided Revascularization.

Background Concerns exist about reliability of pressure-wire-guided coronary revascularization of non-infarct-related arteries (non- IRA ). We investigated whether physiological assessment of non- IRA during the subacute phase of myocardial infarction might be flawed by microcirculatory dysfunction. Methods and Results We analyzed non- IRA that underwent fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance assessment. Microcirculation and hyperemic response were evaluated in 49 acute myocardial infarction patients (59 non- IRA ) and compared with a matched control group of 46 stable angina ( SA ) patients (59 vessels). Time between acute myocardial infarction to physiological interrogation was 5.9±2.4 days. Fractional flow reserve was similar in both groups (0.79±0.11 in non- IRA versus 0.80±0.13 in SA vessels, P=0.527). Lower coronary flow reserve values were found in non- IRA compared with SA vessels (1.77 [1.25-2.76] versus 2.44 [1.63-4.00], P=0.018), primarily driven by an increased baseline flow in non- IRA (rest mean transit time 0.58 [0.32-0.83] versus 0.65 s [0.39-1.20], P=0.045), whereas the hyperemic flow was similar (hyperemic mean transit time 0.26 [0.20-0.42] versus 0.26 s [0.18-0.35], P=0.873). No differences were found regarding index of microcirculatory resistance (15.6 [10.4-21.8] in non- IRA versus 16.7 [11.6-23.6] U in SA vessels, P=0.559). During adenosine infusion, the hyperemic response was similar in both groups (non- IRA versus SA vessels) in terms of the resistive reserve ratio (3.1±2.1 versus 3.7±2.2, P=0.118). Conclusions In the subacute phase of myocardial infarction, non- IRA show an increased baseline flow that may cause abnormal coronary flow reserve despite preserved hyperemic flow. In non- IRA , microcirculatory resistance and adenosine-induced hyperemic response are similar to those found in SA patients. From a physiological perspective, these findings support the use of fractional flow reserve to interrogate non- IRA during the subacute phase of myocardial infarction.

Clinical Outcomes and Prognosis Markers of Patients With Liver Disease Undergoing Transcatheter Aortic Valve Replacement: A Propensity Score-Matched Analysis.

BACKGROUND: Chronic liver disease is a known risk factor for perioperative morbidity and mortality in patients undergoing cardiac surgery. Very little data exist about such patients treated with transcatheter aortic valve replacement (TAVR). Our objective was to evaluate early and late clinical outcomes in a large cohort of patients with liver disease undergoing TAVR and to determine predictive factors of mortality among these patients. METHODS AND RESULTS: This multicenter study collected data from 114 patients with chronic liver disease who underwent TAVR in 12 institutions. Perioperative and long-term outcomes were compared with a cohort of 1118 patients without liver disease after a propensity score-matching analysis (114 matched pairs). In-hospital mortality and vascular and bleeding complications were similar between matched groups. Acute kidney injury was more common in liver disease group (30.8% versus 13.5%; P=0.010). Although cardiovascular mortality was similar between groups (9.4% versus 6.5%; P=0.433) at 2-year follow-up, noncardiac mortality was higher in the liver group (26.4% versus 14.8%; P=0.034). Lower glomerular filtration rate (hazard ratio, 1.10, for each decrease of 5 mL/min in estimated glomerular filtration rate; 95% confidence interval, 1.03-1.17; P=0.005) and Child-Pugh class B or C (hazard ratio, 3.11; 95% confidence interval, 1.47-6.56; P=0.003) were the predictors of mortality in patients with chronic liver disease, with a mortality rate of 83.2% at 2-year follow-up in patients with both factors (estimated glomerular filtration rate <60 mL/min and Child-Pugh B or C). CONCLUSIONS: These findings suggested that TAVR is a feasible treatment for severe aortic stenosis in patients with early-stage liver disease or as bridge therapy before a curative treatment of the hepatic condition. Patients with Child-Pugh class B-C, especially in combination with renal impairment, had a very low survival rate, and TAVR should be carefully considered to avoid a futile treatment. These results may contribute to improve the clinical decision-making process and management in patients with liver disease.

Identification of capillary rarefaction using intracoronary wave intensity analysis with resultant prognostic implications for cardiac allograft patients.

Aims: Techniques for identifying specific microcirculatory structural changes are desirable. As such, capillary rarefaction constitutes one of the earliest changes of cardiac allograft vasculopathy (CAV) in cardiac allograft recipients, but its identification with coronary flow reserve (CFR) or intracoronary resistance measurements is hampered because of non-selective interrogation of the capillary bed. We therefore investigated the potential of wave intensity analysis (WIA) to assess capillary rarefaction and thereby predict CAV. Methods and results: Fifty-two allograft patients with unobstructed coronary arteries and normal left ventricular (LV) function were assessed. Adequate aortic pressure and left anterior descending artery flow measurements at rest and with intracoronary adenosine were obtained in 46 of which 2 were lost to follow-up. In a subgroup of 15 patients, simultaneous RV biopsies were obtained and analysed for capillary density. Patients were followed up with 1-3 yearly screening angiography. A significant relationship with capillary density was noted with CFR (r = 0.52, P = 0.048) and the backward decompression wave (BDW) (r = -0.65, P < 0.01). Over a mean follow-up of 9.3 ± 5.2 years patients with a smaller BDW had an increased risk of developing angiographic CAV (hazard ratio 2.89, 95% CI 1.12-7.39; P = 0.03). Additionally, the index BDW was lower in those who went on to have a clinical CAV-events (P = 0.04) as well as more severe disease (P = 0.01). Conclusions: Within cardiac transplant patients, WIA is able to quantify the earliest histological changes of CAV and can predict clinical and angiographic outcomes. This proof-of-concept for WIA also lends weight to its use in the assessment of other disease processes in which capillary rarefaction is involved.

Combined erythropoietin and iron therapy for anaemic patients undergoing transcatheter aortic valve implantation: the EPICURE randomised clinical trial.

AIMS: The aim of this study was to evaluate, in anaemic patients, the efficacy of erythropoietin (EPO) in reducing red cell (RC) transfusion rates post TAVI. METHODS AND RESULTS: This was a randomised double-blind trial. Patients with severe symptomatic aortic stenosis and concomitant anaemia with an indication for TAVI were randomised (1:1) to receive two weight-based doses of EPO (darbepoetin alfa)+iron or placebo at days 10 (±4 days) and 1 (±1 day) pre TAVI. The primary outcome was the rate of RC transfusions at 30 days. A total of 100 patients (mean age 81±7 years, male 49%) were included: 48 patients received EPO (+iron) and 52 patients received placebo. Baseline characteristics and procedural findings were well balanced between groups except for baseline haemoglobin levels, which were lower in those patients receiving EPO (10.7±1.2 vs. 11.3±1.1 g/dl, p=0.01). The rate of 30-day RC transfusion was similar in both groups (27.1 vs. 25.0% in the EPO and placebo groups, respectively; adjusted odds ratio 1.05, 95% CI: 0.42-2.64, p=0.92), and no differences were observed in the number of RC units per transfused patient (1 [1-3] vs. 2 [1-2] in the EPO and placebo groups, respectively, adjusted p=0.99). Rates of 30-day mortality, stroke, new-onset atrial fibrillation, acute kidney injury, and troponin peak were also similar between groups (p>0.20 for all). CONCLUSIONS: EPO (+iron) administration failed to reduce RC transfusion rates or the per-patient number of transfusion units in anaemic patients undergoing TAVI.

Transcatheter mitral valve implantation for inoperable severely calcified native mitral valve disease: A systematic review.

BACKGROUND: Transcatheter mitral valve implantation (TMVI) for severely calcified native mitral valve disease recently emerged as a treatment option in patients deemed inoperable by conventional techniques. Yet no systematic appraisal currently exists characterizing this novel treatment paradigm. METHODS: A systematic literature review summarizing the clinical, anatomical, peri- and post-procedural characteristics underscoring the technical feasibility of this procedure was performed. RESULTS: Nine publications describing 11 patients [mean age 68 ± 10 years, 82% female, 82% severe mitral stenosis (MS), 18% severe mitral regurgitation (MR)] were identified. Mean STS score, trans-mitral gradient and effective orifice area were 10.5 ± 4.6%, 12 ± 2.4 mm Hg and 0.93 ± 0.06 cm(2) respectively. All patients had severe, circumferential mitral annular calcification on imaging. Dedicated balloon-expanding transcatheter aortic valves were used in 10/11 cases, with 8/11 cases involving a true percutaneous approach with peri-procedural 3D trans-esophageal echocardiographic guidance; 3/11 cases involved an open left atrial approach. Following initial balloon inflation and valve deployment, procedural success rate was 73%, without residual paravalvular leaks (PVL). Successful immediate re-deployment of a 2nd valve was needed in 2 instances following significant PVL detection. Residual trans-valvular gradients ranged from 3 to 7 mm Hg, with no patient demonstrating >grade 2 MR. All patients survived the procedure, with 2 reported deaths on days 10- and 41 post-TMVI being non-cardiac-related. Mid-term clinical follow-up, reported in 8 patients, revealed 6 patients to be alive at 3-months with much improved functional status. CONCLUSIONS: TMVI for native severely calcified mitral valve disease appears technically feasible with acceptable initial acute and mid-term hemodynamic and clinical outcomes. The outcomes of an ongoing, dedicated global Sapien TMVI registry will shed further light on this evolving treatment paradigm.

First-in-Man Experience of a Novel Transcatheter Repair System for Treating Severe Tricuspid Regurgitation.

BACKGROUND: Isolated tricuspid valve surgery is associated with high morbidity and mortality, especially in patients with prior cardiac surgery. The transcatheter Forma Repair System (Edwards Lifesciences, Irvine, California) is designed to provide a surface for native leaflet coaptation to reduce tricuspid regurgitation (TR) by occupying the regurgitant orifice area. OBJECTIVES: This study sought to evaluate the feasibility and exploratory efficacy with this transcatheter repair system for the treatment of severe TR. METHODS: Seven high-risk patients with severe TR and clinical signs of heart failure were declined for surgery and offered transcatheter treatment with this device. All procedures were performed within a cardiac catheterization laboratory or hybrid operating room under general anesthesia with transesophageal echocardiographic guidance. Vascular access was via the left axillary vein. Baseline characteristics, procedural and in-hospital outcomes, as well as 30-day follow-up were prospectively collected. RESULTS: All patients had severe TR and New York Heart Association (NYHA) functional class II to IV (mean age 76 ± 13 years; mean logistic EuroSCORE 25.7 ± 17.4%), and underwent device implantation to improve tricuspid leaflet coaptation, thereby reducing TR. Device implantation was successful without procedural complications in all patients, with significant reductions in TR severity (moderate in 3 patients and mild in 4 patients). Median hospital length of stay was 4 days. At 30-day follow-up, all patients but 1 demonstrated improvements in NYHA functional status (to class II) with pronounced reductions in the presence and severity of peripheral edema. TR severity was assessed as being moderate at 30-day transthoracic echocardiography follow-up in all patients. No complications related to the device or vascular access were observed during follow-up. CONCLUSIONS: A transcatheter-based treatment option for severe TR appears safe and feasible with this repair system. Improvements in TR severity were documented in all patients, which were accompanied by improvements in peripheral edema and functional status.

Transcatheter Valve-in-Valve and Valve-in-Ring for Treating Aortic and Mitral Surgical Prosthetic Dysfunction.

Bioprosthetic valve use has increased significantly. Considering their limited durability, there will remain an ongoing clinical need for repairing or replacing these prostheses in the future. The current standard of care for treating bioprosthetic valve degeneration involves redo open-heart surgery. However, repeat cardiac surgery may be associated with significant morbidity and mortality. With the rapid evolution of transcatheter heart valve therapies, the feasibility and safety of implanting a transcatheter heart valve within a failed tissue valve has been established. We review the historical perspective of transcatheter valve-in-valve therapy, as well as the main procedural challenges and clinical outcomes associated with this new less invasive treatment option.

Initial Experience of Transcatheter Mitral Valve Replacement With a Novel Transcatheter Mitral Valve: Procedural and 6-Month Follow-Up Results.

BACKGROUND: There are scarce data available on transcatheter mitral valve replacement (TMVR), and these have been limited to procedural results, with no follow-up status reported. OBJECTIVES: The goal of this study was to evaluate the feasibility, procedural results, and 6-month follow-up outcomes after TMVR with a mitral transcatheter heart valve (Fortis, Edwards Lifesciences, Irvine, California). METHODS: We report a series of 3 patients (mean age 71 ± 9 years, 2 men) who had TMVR under a compassionate clinical use program. All patients treated had functional mitral regurgitation (MR) secondary to ischemic cardiomyopathy (prior bypass surgery in all cases; left ventricular ejection fraction between 25% and 30%) and were considered to be at very high surgical risk (mean Society of Thoracic Surgeons score: 9.3). RESULTS: The procedure was performed through the transapical approach, and the valve was successfully implanted in all cases, with no major complications. At hospital discharge, echocardiographic evaluation revealed trace residual MR in 2 patients and no MR in 1 patient. The mean transvalvular mitral gradient was ≤4 mm Hg in all patients. At the 3-month follow-up, the valve function remained unchanged, and transesophageal echocardiography and computed tomography showed no structural failures. All patients had improvements in functional status, in exercise capacity as evaluated by 6-min walk test, and in quality of life. At 6-month follow-up, all patients remain alive, without hospital readmission for heart failure and with New York Heart Association functional class ≤II. CONCLUSIONS: TMVR with this valve is feasible and is associated with good outcomes. Optimal valve functional results were obtained acutely and were sustained at 6-month follow-up in all patients. Further studies with a larger number of patients and longer follow-up are warranted.

Myocardial Injury After Transaortic Versus Transapical Transcatheter Aortic Valve Replacement.

BACKGROUND: The release of cardiac biomarkers of myocardial injury after transcatheter aortic valve replacement (TAVR) is common, but no data exist on patients undergoing TAVR through a transaortic approach. We aimed to evaluate the incidence and prognostic significance of the increase in cardiac biomarkers in nontransfemoral TAVR candidates, comparing transaortic and transapical approaches. METHODS: After excluding patients deemed suitable for transfemoral TAVR, 251 consecutive patients (transaortic, 45; transapical, 206) were prospectively evaluated. Creatine kinase-myocardial band and cardiac troponin T levels were measured at baseline and at 6, 12, 24, 48, and 72 hours after TAVR. Baseline and 6- to 12-month echocardiographic and clinical follow-up were performed. RESULTS: After TAVR, cardiac troponin T increased above the upper normal values in all patients (peak value 0.64 µg/L [IQR, 0.39 to 1.03 µg/L]), whereas creatine kinase-myocardial band levels increased in 88% of patients (transaortic 51%, transapical 96%, p < 0.001; peak value 20.1 µg/L [interquartile range, 14.3 to 31.6 µg/L]). Compared with the transaortic approach, the transapical approach was associated with a greater rise in both cardiac biomarkers (p < 0.001 for both), and a lesser improvement in left ventricular ejection fraction (p = 0.058) and global longitudinal strain (p = 0.039) at 6- to 12-month follow-up. Greater increases of cardiac troponin T levels were independently associated with 30-day and 1-year overall and cardiovascular mortality (p < 0.001 for all). A 15-fold rise in cardiac troponin T levels was the optimal threshold for determining poorer outcomes (p < 0.001). CONCLUSIONS: Periprocedural TAVR-related myocardial injury in nontransfemoral candidates was demonstrated in all patients, but the transapical approach was associated with significantly greater myocardial injury compared with the transaortic approach. A higher degree of myocardial injury translated into reduced left ventricular function improvement and lower early and midterm survival rates.

Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial.

RATIONALE: Refractory angina constitutes a clinical problem. OBJECTIVE: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina. METHODS AND RESULTS: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm. CONCLUSIONS: Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.

Comparison of clinical features of left-sided infective endocarditis involving previously normal versus previously abnormal valves.

Native valve infective endocarditis (IE) in patients with normal valves has increased in the last decades. Whether patients with normal valves present a similar prognosis to those with pathologic valves is unresolved. Our aim is to describe epidemiologic and clinical differences between patients with left-sided IE and normal valves and those with native pathologic valves. We analyzed 945 consecutive episodes of IE, 435 of which involved left-sided nonprosthetic IE. They were classified into 2 groups: episodes in normal valves (normal group, n=173) and episodes in pathologic valves (abnormal group, n=262). Patients in the normal group were younger, Staphylococcus aureus and Streptococcus bovis were more frequently isolated, and vegetations were more frequently found. Heart failure, septic shock, and the need for surgery or death were more common. Multivariate analysis identified the following as factors independently associated with normal valve IE: age<65 years, S bovis, S aureus, heart failure, and vegetation detection. Factors independently associated with in-hospital events included S aureus, periannular complications, heart failure, and septic shock development. In conclusion, compared with patients with abnormal valve IE, patients with IE on normal valves were younger, had a more virulent microbiological profile, developed heart failure and septic shock more frequently, needed more surgical procedures, and had worse prognosis.