New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Cardiac Structural and Functional Remodeling After Transcatheter Mitral Valve in Valve Implantation: Early Changes and Prognostic Significance.

Background: Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs. The degree of cardiac remodeling assessed by echocardiography has been shown to have prognostic implications in degenerative mitral regurgitation patients undergoing MV surgery. The impact of transcatheter MViV in patients with degenerative bioprosthetic MV failure on cardiac remodeling and its associated prognosis remains undescribed. Objectives: The aim of this study is to describe the early anatomic and functional changes of the left-sided chambers and right ventricle by echocardiography posttranscatheter MViV intervention and their impact on mortality outcomes. Additionally, we sought to analyze the outcome of heart failure in bioprosthetic MV failure patients undergoing transcatheter MViV replacement. Methods: We analyzed consecutive patients undergoing MViV intervention for symptomatic bioprosthetic MV failure. Echocardiograms before intervention and within 100 days postintervention were analyzed. A chart review was performed to obtain baseline characteristics, follow-up visits, 30-day heart failure and 1-year all-cause mortality outcomes. Results: A total of 62 patients (mean age 69 ± 13 years, 61% male) were included in the study. Most patients were undergoing MViV intervention for prosthetic mitral stenosis n = 48 (77.4%) and the rest for mitral regurgitation or mixed disease. Compared with baseline, significant reductions were observed in median left atrial volume (LAV; 103 [81-129] ml vs. 95.2 [74.5-117.5] ml, p < 0.01) and mean (SD) left atrial conduit strain (9.1% ± 5.2% vs. 10.8% ± 4.8%, p = 0.039) within 100 days postintervention. Early reduction in right ventricular free wall global longitudinal strain and fractional area change also occurred postintervention. No significant change in left ventricular chamber dimensions or ejection fraction was observed. During the 1-year follow up period, 5 (8%) patients died. While baseline LAV was not associated with 1-year all-cause mortality (OR 0.98 CI 0.95-1.01; p = 0.27), a change in LAV in the follow up period was associated with all-cause mortality at 1 year (OR 1.06 CI 1.01-1.12; p = 0.023). At 30 days postintervention, 65% of patients had an improvement in their New York Heart Association functional class. Conclusion: In this retrospective study of patients undergoing transcatheter MViV intervention for failed bioprosthetic MVs, early reverse remodeling of the left atrium occurs within 100 days postintervention and reduction in LAV is associated with reduced all-cause mortality at 1 year. In addition, there is significant improvement in heart failure symptoms at 30 days following intervention but further investigation into the longitudinal remodeling changes and long-term outcomes is needed.

Age-Stratified Surgical Aortic Valve Replacement for Aortic Stenosis.

BACKGROUND: The management of aortic stenosis has evolved to stratification by age as reflected in recent societal guidelines. We evaluated age-stratified surgical aortic valve replacement (SAVR) trends and outcomes in patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) from The Society of Thoracic Surgeons Adult Cardiac Surgery Database. METHODS: This cohort included adults (≥18 years) undergoing SAVR for severe aortic stenosis between July 2011 and December 2022. Comparisons were stratified by age (<65 years, 65-79 years, ≥80 years) and BAV or TAV status. Primary end points included operative mortality, composite morbidity and mortality, and permanent stroke. Observed to expected ratios by The Society of Thoracic Surgeons predicted risk of mortality were calculated. RESULTS: In total, 200,849 SAVR patients (55,326 BAV [27.5%], 145,526 TAV [72.5%]) from 1238 participating hospitals met study criteria. Annual SAVR volumes decreased by 45% (19,560 to 10,851) during the study period. The decrease was greatest (96%) for patients ≥80 years of age (4914 to 207). The relative prevalence of BAV was greater in younger patients (<65 years, 69,068 [49.5% BAV]; 65-79 years, 104,382 [19.1% BAV]; ≥80 years, 27,399 [4.5% BAV]). The observed mortality in <80-year-old BAV patients (<65 years, 1.08; 65-79 years, 1.21; ≥80 years, 3.68) was better than the expected mortality rate (<65 years, 1.22; 65-79 years, 1.54; ≥80 years, 3.14). CONCLUSIONS: SAVR volume in the transcatheter era has decreased substantially, particularly for patients ≥80 years old and for those with TAV. Younger patients with BAV have better than expected outcomes, which should be carefully considered during shared decision-making in the treatment of aortic stenosis. SAVR should remain the preferred therapy in this population.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Characterization of Screen Failures Among Patients Evaluated for Transcatheter Tricuspid Valve Repair (TriSelect-Study).

BACKGROUND: Transcatheter tricuspid valve repair (TTVr) has significantly expanded treatment options for tricuspid regurgitation (TR). However, a sizeable proportion of patients are still declined for TTVr and little is known about their clinical characteristics and cardiac morphology. OBJECTIVES: This study sought to characterize patients who screen fail for TTVr with respect to their clinical characteristics and cardiac morphology. METHODS: A total of 547 patients were evaluated for TTVr between January 2016 to December 2021 from 3 centers in the United States and Germany. Clinical records and echocardiographic studies were used to assess medical history and right ventricular (RV) and tricuspid valve (TV) characteristics. RESULTS: Median age was 80 (IQR: 74-83) years and 60.0% were female. Over half (58.1%) were accepted for TTVr. Of those who were deemed unsuitable for TTVr (41.9%), the most common exclusion reasons were anatomical criteria (56.8%). In the regression analysis, RV and right atrial size, TV coaptation gap, and tethering area were identified as independent screen failure predictors. Other rejection reasons included clinical futility (17.9%), low symptom burden (12.7%), and technical limitations (12.7%). Most of the excluded patients (71.6%) were managed conservatively with medical therapy, while a small number either proceeded to TV surgery (22.3%) or subsequently became eligible for transcatheter tricuspid valve replacement in later available clinical trials in the United States (6.1%). CONCLUSIONS: The majority of TTVr screen failure patients are excluded due to TV, right atrial, and RV enlargement. However, a significant proportion is excluded due to clinical futility. These identifiable anatomical and clinical characteristics emphasize the importance of earlier referral and intervention of TR and the need for continued innovation of Transcatheter tricuspid valve interventions.

Acupuncture after valve surgery is feasible and shows promise in reducing postoperative atrial fibrillation: The ACU-Heart pilot trial.

Objective: Acupuncture is an effective treatment for arrythmias and postoperative symptoms but has not been investigated after cardiac surgery. Acupuncture After Heart Surgery is a prospective, randomized, controlled pilot trial of daily inpatient acupuncture or standard care after valve surgery with the primary end point being feasibility and secondary end points being reduction in postoperative atrial fibrillation incidence and postoperative symptoms. Methods: A total of 100 patients without a history of atrial fibrillation underwent primary valve surgery via sternotomy and randomized 1:1 to acupuncture (51) or standard care (49). The acupuncture group received daily inpatient sessions starting on postoperative day 1. Postoperative symptoms (pain, nausea, stress, anxiety) were assessed once daily in the standard care group and before/after daily intervention in the acupuncture group. The groups were comparable except for age (acupuncture: 55.6 ± 11.4 years, standard care: 61.0 ± 9.3 years; P = .01). Results: The Acupuncture After Heart Surgery pilot trial met primary and secondary end points. There were no adverse events. An average of 3.8 (±1.1) acupuncture sessions were delivered per patient during a mean hospital stay of 4.6 days (±1.3). Acupuncture was associated with a reduction in pain, nausea, stress, and anxiety after each session (P < .0001), and patients receiving acupuncture had reduced postoperative stress and anxiety across admission compared with standard care (P = .049 and P = .036, respectively). Acupuncture was associated with reduced postoperative atrial fibrillation incidence (acupuncture: 7 [13.7%], standard care: 16 [32.7%]; P = .028), fewer discharges on amiodarone (acupuncture: 5 [9.8%], standard care: 13 [26.5%]; P = .03), and fewer hours in the intensive care unit (acupuncture: 30.3 ± 10.0, standard care: 37.0 ± 22.5; P = .057). Conclusions: Acupuncture after valve surgery is feasible, is well tolerated, and has clinical benefit. The reduction noted in postoperative atrial fibrillation incidence will inform larger trials designed to further investigate the impact of acupuncture on postoperative atrial fibrillation and medical outcomes.

1-Year Outcomes of Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study.

BACKGROUND: Tricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative. OBJECTIVES: The Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences). METHODS: Patients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events. RESULTS: The 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively. CONCLUSIONS: One-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes.

Unique technical challenges in patients undergoing TAVR for failed aortic homografts.

OBJECTIVE: Surgical reoperation for aortic homograft structural valve degeneration (SVD) is a high-risk procedure. Transcatheter aortic valve replacement (TAVR) for homograft-SVD is an alternative to reoperation, but descriptions of implantation techniques are limited. This study compares outcome in patients undergoing into two groups by the type of previously implanted aortic valve prosthesis: TAVR for failed aortic homografts (TAVR-H) or for stented aortic bioprostheses (TAVR-BP). METHODS: From 2015 to 2017, TAVR was performed in 41 patients with SVD. Thirty-three patients in the TAVR-BP group (six for SVD of valved conduits), and eight patients in the TAVR-H group. The Valve Academic Research Consortium criteria were used for outcome reporting purposes. RESULTS: The patients with TAVR-BP had predominant prosthetic stenosis (94%, p = .002), whereas TAVR-H individuals presented mostly with regurgitation (88%, p = <.001). Patients with TAVR-H received: Sapien-3 (6), Sapien-XT (1), and CoreValve (1) devices. Low, 40% ventricular fixation in relation to homograft annulus was attempted to anchor the prosthesis on the homograft suture-line. One patient with TAVR-BP experienced intraoperative distal prosthesis migration and Type-B aortic dissection, and two patients in the TAVR-H group had late postoperative proximal device migration. In both groups, there was zero 30-day mortality, stroke, or pacemaker implantation. CONCLUSIONS: TAVR for failing aortic homografts may be a feasible and safe alternative to high-risk surgical reintervention. Precise, 40%-ventricular device positioning appears crucial for prevention of late paravalvular leak/late prosthesis migration and minimizing the risk of repeat surgical intervention.

Prevalence of atrial fibrillation before cardiac surgery and factors associated with concomitant ablation.

OBJECTIVE: Surgical ablation for atrial fibrillation concomitant with cardiac surgery is now a Class I recommendation for selected patients. Understanding how the revised recommendations will affect appropriate use of surgical ablation is challenging because the reported prevalence of preoperative atrial fibrillation depends on the definition used. The objective was to determine the prevalence of atrial fibrillation in the 3 years before cardiac surgery and the rate of concomitant surgical ablation. METHODS: Patients with and without a diagnosis of atrial fibrillation in the 3 years before surgical coronary artery bypass, aortic valve replacement, or mitral valve replacement/repair were identified in the 2014 Medicare Standard Analytical File. RESULTS: Patients had prior atrial fibrillation in 28.4% of 79,134 cardiac surgeries. Prior atrial fibrillation was associated with risk factors for increased cardiac surgical morbidity/mortality, including recent heart failure, renal failure, and lung disease. Black patients were less likely to have prior atrial fibrillation but more likely to have had infrequent care for it. Isolated coronary artery bypass had the lowest prevalence but highest absolute number of prior atrial fibrillation cases. Concomitant surgical ablation was performed in 22.1% of patients with prior atrial fibrillation. Patients with mitral valve surgery were 3-fold more likely to receive surgical ablation. Women were less likely to have prior atrial fibrillation but less likely to have surgical ablation when they did. CONCLUSIONS: Medicare beneficiaries had a substantially higher prevalence of atrial fibrillation diagnoses in the 3 years before cardiac surgery than previously published rates of preoperative atrial fibrillation. Concomitant surgical ablation was performed in less than one-quarter of patients with atrial fibrillation undergoing cardiac surgery for other indications.

Compassionate Use of the PASCAL Transcatheter Valve Repair System for Severe Tricuspid Regurgitation: A Multicenter, Observational, First-in-Human Experience.

OBJECTIVES: The purpose of this observational first-in-human experience was to investigate the feasibility and safety of the PASCAL transcatheter valve repair system and its impact on short-term clinical outcomes in patients with severe tricuspid regurgitation (TR). BACKGROUND: Transcatheter repair of severe TR is a promising treatment option for patients at prohibitive surgical risk. Large leaflet coaptation gaps and tethering represent common features that challenge the application of transcatheter repair techniques. METHODS: Twenty-eight patients with severe TR were treated with the PASCAL system in a compassionate use experience at 6 sites. All patients had heart failure due to severe TR and were deemed at high surgical risk by institutional heart teams. The primary outcome was procedural success, defined as the implantation of at least 1 device with post-procedural TR grade ≤2+, without mortality or conversion to surgery. RESULTS: All patients (mean age 78 ± 6 years, 54% women) were at high surgical risk (mean European System for Cardiac Operative Risk Evaluation II score 6.2 ± 5.2%). TR etiology was functional in 92%, with mean tricuspid annular diameter of 49.5 ± 6 mm and mean coaptation gap of 6.9 ± 3 mm. Procedural success was 86%, with 1.4 ± 0.6 devices implanted per patient. There were no intraprocedural complications. At 30-day follow-up, mortality was 7.1%, 88% of patients were in New York Heart Association functional class I or II, with TR grade ≤2+ in 85%. There were 2 single-leaflet device attachments, which were managed conservatively. Six-min walk distance improved from 240 m (interquartile range: 172 to 337 m) to 335 m (interquartile range: 251 to 385 m) (p < 0.001). CONCLUSIONS: This first-in-human experience evaluating transcatheter tricuspid repair with the PASCAL system demonstrated high procedural success, acceptable safety, and significant clinical improvement. Larger prospective studies with long-term follow-up are needed to confirm these initial promising results and further define the impact of PASCAL tricuspid repair on clinical outcomes.

Transcatheter Mitral Valve Replacement with Intrepid.

Transcatheter mitral valve replacement with the Intrepid device is intended for patients who need mitral valve replacement and who are at an increased risk for conventional surgery. The early published results of the early feasibility trial are reviewed as well as device design and the implant procedure. The Apollo trial is reviewed: a randomized trial of the Intrepid device versus conventional surgery including a single arm study for inoperable patients. The mitral valve structure, pathophysiology, and postimplant physiology pose unique hurdles for any transcatheter implant.

Coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesized that coronary microvascular dysfunction is common in these patients. In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF [left ventricular (LV) ejection fraction ≥ 50% and with clinical HF] were compared with similar patients without HFpEF. Patients with ≥50% stenosis were excluded, and coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were measured after adenosine administration using a guidewire, with CFR ≤ 2 and IMR ≥ 23 being abnormal. Baseline characteristics and CFR and IMR were compared in 30 HFpEF patients and 14 control subjects. Compared with control subjects, HFpEF patients were older (65.4 ± 9.6 vs. 55.1 ± 3.1 yr, P < 0.01), had higher numbers of comorbidities (4.4 ± 1.5 vs. 2.6 ± 1.9, P = 0.002), had higher median B-type natriuretic peptide [161 (interquartile range: 75-511) pg/dl vs. 37 (interquartile range: 18.5-111) pg/dl, P < 0.01], and had higher LV end-diastolic pressure (17.8 ± 4.2 vs. 8.4 ± 4.2, P < 0.01). HFpEF patients had lower CFR (2.55 ± 1.60 vs. 3.84 ± 1.89, P = 0.024) and higher IMR (26.7 ± 10.3 vs. 19.7 ± 9.7 units, P = 0.037) than control subjects. Most (71.4%) control subjects had normal coronary physiology, whereas 36.7% of HFpEF patients had both abnormal CFR and IMR and another 36.7% had either abnormal CFR or IMR. In conclusion, this is the first study that has reported invasively determined CFR and IMR in HFpEF patients. We demonstrated the presence of four distinct coronary physiology groups in HFpEF patients. Investigation into the potential mechanisms for these findings is needed. NEW & NOTEWORTHY In this prospective observational study of patients with heart failure with preserved ejection fraction (HFpEF), we found that patients with HFpEF had more abnormalities of coronary flow and resistance than asymptomatic control patients, indicating that coronary microvascular dysfunction may play a role in the HFpEF disease process.

Association of Transcatheter Aortic Valve Replacement With 30-Day Renal Function and 1-Year Outcomes Among Patients Presenting With Compromised Baseline Renal Function: Experience From the PARTNER 1 Trial and Registry.

Importance: The frequency of baseline renal impairment among high-risk and inoperable patients with severe aortic stenosis undergoing a transcatheter aortic valve replacement (TAVR) and the effect of TAVR on subsequent renal function are, to our knowledge, unknown. Objective: To determine the effect of TAVR among patients with baseline renal impairment. Design, Setting, and Participants: This substudy of patients with baseline renal impairment (estimated glomerular filtration rate [eGFR] ≤ 60 mL/min) and paired baseline and 30-day measures of renal function undergoing TAVR in the PARTNER 1 trial and continued access registries was conducted in 25 centers in the United States and Canada. Main Outcomes and Measures: Patients were categorized with improved eGFR (30-day follow-up eGFR≥10% higher than baseline pre-TAVR), worsened eGFR (≥10% lower), or no change in renal function (neither). Baseline characteristics, 30-day to 1-year all-cause mortality, and repeat hospitalization were compared. Multivariable models were constructed to identify predictors of 1-year mortality and of improvement/worsening in eGFR. Results: Of the 821 participants, 401 (48.8%) were women and the mean (SD) age for participants with improved, unchanged, or worsening eGFR was 84.90 (6.91) years, 84.37 (7.13) years, and 85.39 (6.40) years, respectively. The eGFR was 60 mL/min or lower among 821 patients (72%), of whom 345 (42%) improved, 196 (24%) worsened, and 280 (34%) had no change at 30 days. There were no differences in baseline age, body mass index, diabetes, chronic obstructive pulmonary disease, coronary artery disease, peripheral arterial disease, hypertension, pulmonary hypertension, renal or liver disease, New York Heart Association III/IV symptoms, transaortic gradient, left ventricular ejection fraction, or procedural characteristics. The group with improved eGFR had more women, nonsmokers, and a lower cardiac index. Those with worsening eGFR had a higher median Society of Thoracic Surgeons score and left ventricle mass. From 30 days to 1 year, those with improved eGFR had no difference in mortality or repeat hospitalization. Those with worsening eGFR had increased mortality (25.5% vs 19.1%, P = .07) but no significant increases in repeat hospitalization or dialysis. Predictors of improved eGFR were being female (odds ratio [OR], 1.38; 95% CI, 1.03-1.85; P = .03) and nonsmoking status (OR, 1.49; 95% CI, 1.11-1.01; P = .01); predictors of worsening eGFR were baseline left ventricle mass (OR, 1.00; 95% CI, 1.00-1.01; P = .01), smoking (OR, 1.51; 95% CI, 1.06-2.14; P = .02), and age (OR, 1.03; 95% CI, 1.00-1.05; P = .05); and predictors of 1-year mortality were baseline left ventricular ejection fraction (OR, 0.98; 95% CI, 0.97-0.99; P = .003), baseline eGFR (OR, 0.98; 95% CI, 0.96-0.99; P < .001), and worsening eGFR vs no change in eGFR (OR, 1.51; 95% CI, 1.02-2.24; P = .04). Conclusions and Relevance: Baseline renal impairment was frequent among patients who underwent TAVR. While improved eGFR did not improve 1-year outcomes, worsening eGFR was associated with increased mortality. Trial Registration: clinicaltrials.gov Identifier: NCT00530894.

Early Feasibility Study of a Transcatheter Tricuspid Valve Annuloplasty: SCOUT Trial 30-Day Results.

BACKGROUND: The SCOUT (Percutaneous Tricuspid Valve Annuloplasty System for Symptomatic Chronic Functional Tricuspid Regurgitation) trial is a prospective, single-arm, multicenter, early feasibility study of a novel transcatheter device to plicate the tricuspid annulus (TA) and reduce tricuspid regurgitation (TR). OBJECTIVES: This study tested the feasibility and safety of a novel transcatheter device and assessed its early performance and functional outcomes. METHODS: Between November 2015 and June 2016, 15 patients with New York Heart Association (NYHA) functional class ≥II and moderate or greater functional TR were enrolled. Primary performance and safety endpoint outcomes were technically successful at 30 days with no reintervention. Echocardiographic measurements (TA diameter, effective regurgitant orifice area [EROA], left ventricular stroke volume [LVSV]) and quality-of-life (QoL) measurements (NYHA functional class, Minnesota Living with Heart Failure Questionnaire [MLHFQ], and 6-min walk test [6MWT]) were performed at baseline and 30 days. RESULTS: All patients (mean 73.2 ± 6.9 years of age, 87% female) underwent successful device implantation with no deaths, strokes, bleeding, tamponade, or valve reintervention. Technical success rate at 30 days was 80%, with 3 single-pledget annular detachments without reintervention. In the remaining 12 patients, there were significant reductions in TA (12.3 ± 3.1 cm2 to 11.3 ± 2.7 cm2, respectively; p = 0.019) and EROA (0.51 ± 0.18 cm2 vs. 0.32 ± 0.18 cm2, respectively; p = 0.020), with significant increase in LVSV (63.6 ± 17.9 ml vs. 71.5 ± 25.7 ml, respectively; p = 0.021). In the intention-to-treat cohort, there were significant improvements in NYHA functional class (≥1 class, p = 0.001), MLHFQ (47.4 ± 17.6 to 20.9 ± 14.8; p < 0.001), and 6MWT (245.2 ± 110.1 to 298.0 m ± 107.6 m; p = 0.008). CONCLUSIONS: The 30-day results of the SCOUT trial confirmed the safety of the novel transcatheter device, which reduced TA and EROA, increased LVSV, and improved QoL. (Early Feasibility of the Mitralign Percutaneous Tricuspid Valve Annuloplasty System (PTVAS) Also Known as TriAlign [SCOUT]; NCT02574650.).

PreSERVE-AMI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intracoronary Administration of Autologous CD34+ Cells in Patients With Left Ventricular Dysfunction Post STEMI.

RATIONALE: Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. OBJECTIVE: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. METHODS AND RESULTS: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. CONCLUSIONS: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364.

Lack of Association Between Extracranial Carotid and Vertebral Artery Disease and Stroke After Transcatheter Aortic Valve Replacement.

BACKGROUND: Carotid artery stenosis is a risk factor for stroke after surgical aortic valve replacement, but it is unknown whether carotid and vertebral artery disease impacts the risk of stroke after transcatheter aortic valve replacement (TAVR). METHODS: We reviewed 294 consecutive cases of TAVR at a tertiary care medical centre. Thirty-one patients without preoperative carotid/vertebral duplex ultrasonograms were excluded. Carotid or vertebral artery disease was defined on the basis of >50% stenosis. Outcomes were stroke within 30 days after TAVR, 30-day mortality, and overall survival. RESULTS: Fifty-one patients (19%) had at least 50% stenosis of a carotid or vertebral artery. The carotid and vertebral artery disease group had higher rates of coronary artery disease, previous coronary artery bypass surgery, and peripheral artery disease compared with the control group. Transfemoral access was less common in the carotid and vertebral artery disease group (55% vs 77%; P < 0.01). Stroke occurred in 6.8% of patients (n = 18) within 30 days after TAVR, but no patients in the carotid and vertebral artery disease group had a stroke. The presence of at least 50% stenosis of a carotid or vertebral artery was not predictive of stroke by logistic regression. There was no difference in 30-day mortality (10% vs 4%; P = 0.11) and overall survival (log-rank test P = 0.84) between the groups. CONCLUSIONS: The presence or absence of carotid or vertebral artery stenosis was not significantly related to the occurrence of stroke after TAVR. Routine screening for carotid and vertebral artery disease before TAVR does not appear justified.

Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study.

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34+ stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI (N = 167), patients treated with autologous CD34+ stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing placebo, low dose (1 × 105 CD34/kg body weight), and high dose (5 × 105 CD34/kg) using intramyocardial delivery into the ischemic zone following NOGA® mapping. To obtain longer-term safety and efficacy in these patients, we compiled data of major adverse cardiac events (MACE; death, myocardial infarction, acute coronary syndrome, or heart failure hospitalization) up to 24 months as well as angina and quality of life assessments in patients who consented for 24-month follow-up. A total of 167 patients with class III-IV refractory angina were randomized and completed the injection procedure. The low-dose-treated patients had a significant reduction in angina frequency (p = 0.02, 0.035) and improvements in exercise tolerance testing (ETT) time (p = 0.014, 0.017) compared to the placebo group at 6 and 12 months. At 24 months, patients treated with both low-and high-dose CD34+ cells had significant reduction in angina frequency (p = 0.03). At 24 months, there were a total of seven deaths (12.5%) in the control group versus one (1.8%) in the low-dose and two (3.6%) in the high-dose (p = 0.08) groups. At 2 years, MACE occurred at a rate of 33.9%, 21.8%, and 16.2% in control, low-, and high-dose patients, respectively (p = 0.08). Autologous CD34+ cell therapy was associated with persistent improvement in angina at 2 years and a trend for reduction in mortality in no-option patients with refractory angina.

Prospective Multicenter Evaluation of the Direct Flow Medical Transcatheter Aortic Valve System: 12-Month Outcomes of the Evaluation of the Direct Flow Medical Percutaneous Aortic Valve 18F System for the Treatment of Patients With Severe Aortic Stenosis (DISCOVER) Study.

OBJECTIVES: The aim of this study was to assess the 1-year outcome after transcatheter aortic valve replacement (TAVR) of the Direct Flow Medical (DFM) valve in patients with severe symptomatic aortic stenosis who were contraindicated or high risk for surgery. BACKGROUND: The DFM transcatheter heart valve is a new-generation, nonmetallic aortic valve with a pressurized support structure and conformable double-ring annular sealing delivered through an 18-F sheath. The device allows repositioning, retrieval, and assessment of valve performance before permanent implantation. METHODS: A prospective multicenter European registry was set up to determine the safety and performance of the valve in 100 consecutive patients (10 centers). Echocardiographic and angiographic data were evaluated by an independent core laboratory, and adverse events were adjudicated by a clinical events committee using Valve Academic Research Consortium criteria. RESULTS: Patients were 83.1 ± 5.9 years of age and had a logistic EuroSCORE of 22.5 ± 11.3% and a Society of Thoracic Surgeons score of 9.7 ± 8.7%. Correct valve positioning was obtained in 99% of cases with a combined 30-day safety endpoint at 10%, including major stroke in 5.0%, major vascular complications in 2.0%, and death in 1%. At 12 months, 95% of patients were in New York Heart Association functional class I or II. Freedom from any death was 90%, and freedom from any death or major stroke was 85%. Echocardiography demonstrated none/trace to mild aortic regurgitation in 100% of patients and an unchanged mean aortic gradient of 12.2 ± 6.6 mm Hg and effective orifice area of 1.6 ± 0.4 cm(2). CONCLUSIONS: At 1 year, the DFM transcatheter heart valve had durable hemodynamics. This study demonstrates that the low rate of early complications and the low risk of significant aortic regurgitation translated into midterm clinical benefit.