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.

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.

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.

Paravalvular regurgitation after conventional aortic and mitral valve replacement: A benchmark for alternative approaches.

OBJECTIVE: Paravalvular regurgitation is a known complication after transcatheter and sutureless aortic valve replacement. Paravalvular regurgitation also may develop in patients undergoing percutaneous mitral valve replacement. There are few studies on contemporary surgical valve replacement for comparison. We sought to determine the contemporary occurrence of paravalvular regurgitation after conventional surgical valve replacement. METHODS: We performed a single-center retrospective database review involving 1774 patients who underwent valve replacement surgery from April 2004 to December 2012: aortic in 1244, mitral in 386, and combined aortic and mitral in 144. Follow-up echocardiography was performed in 73% of patients. Patients with endocarditis were analyzed separately from noninfectious paravalvular leaks. Statistical comparisons were performed to determine differences in paravalvular regurgitation incidence and survival. RESULTS: During follow-up, 1+ or greater (mild or more) paravalvular regurgitation occurred in 2.2% of aortic cases and 2.9% of mitral cases. There was 2+ or greater (moderate or more) paravalvular regurgitation in 0.9% of aortic and 2.2% of mitral cases (P = .10). After excluding endocarditis, late noninfectious regurgitation 2+ or greater was detected in 0.5% of aortic and 0.4% of mitral cases (P = .93); there were no reoperations or percutaneous closures for noninfectious paravalvular regurgitation. CONCLUSIONS: In an academic medical center, the overall rate of paravalvular regurgitation is low, and late clinically significant noninfectious paravalvular regurgitation is rare. The benchmark for paravalvular regurgitation after conventional valve replacement is high and should be considered when evaluating patients for transcatheter or sutureless valve replacement.

Percutaneous closure of perivalvular mitral regurgitation: how should the interventionalists and the echocardiographers communicate?

There is considerable interest in percutaneous closure of perivalvular leaks without the need for repeat surgery. Successful percutaneous closure of these defects requires extensive planning and coordination before and during the procedure. However, there is no standardized description of valve pathology in the presence of a prosthetic valve, which adds to the challenge of communication. Transesophageal echocardiography is ideally suited to guide percutaneous mitral valve procedures, because of the proximity of the mitral valve to the esophagus. Successful percutaneous procedures of the mitral valve require teamwork. Both the interventionalist and the echocardiographer must have great familiarity with mitral valve anatomy, structure, and function, and they must know how to effectively communicate with each other. The authors review the relevant periprocedural mapping of the mitral valve and provide guidance to echocardiographers and interventionalists on effective ways to communicate during percutaneous perivalvular mitral leak closures to accomplish a successful outcome.

A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study.

Preclinical trials indicate that CD34+ cells represent an effective angiogenic stem cell component. Early-phase clinical trials suggest that intramyocardial administration of autologous CD34+ cells may improve functional capacity and symptoms of angina. RENEW is a pivotal phase 3 trial designed to determine the efficacy of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ stem cells for the treatment for patients with refractory angina and chronic myocardial ischemia. Patients (n = 444) receiving maximally tolerated antianginal therapies and lacking conventional revascularization options with Canadian Cardiovascular Society class III or IV angina and ischemia on stress testing will be randomized 2:1:1 to cell therapy (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial injection of 1 × 10(5) autologous CD34(+) cells/kg), active control (G-CSF-mediated stem cell mobilization, apheresis, and intramyocardial placebo injection), or open-label standard of care. The primary efficacy end point is change in exercise treadmill time in the treated vs active control patients, with 90% power to detect a 60-second difference in exercise time between cell-treated (n = 200) and active control (n = 100) patients. Key secondary end points include total number of anginal episodes per week and the incidence of independently adjudicated major adverse cardiac events and serious adverse events. RENEW will be the first adequately powered study aimed at definitively determining the efficacy of a cell therapy (intramyocardially delivered autologous CD34+ cells) for improvement of functional capacity in patients with refractory angina.

Feasibility study of the RenalGuard™ balanced hydration system: a novel strategy for the prevention of contrast-induced nephropathy in high risk patients.

BACKGROUND: Contrast-induced nephropathy (CIN) is a frequent complication following angiographic procedures with significant impact on healthcare costs, and long-term outcomes. Multiple reno-protective strategies have been studied but few have shown benefit in prospective randomized studies beyond limiting the exposure to iodinated contrast and adequate intravenous. We studied the performance and safety of a novel system designed to achieve precise real-time high volume fluid balance using a closed loop hydration monitoring and infusion system. METHODS: This prospective, multi-center, FDA approved phase II feasibility study was designed to evaluate the safety and the performance of the RenalGuard matched hydration system. Between October 2006 and November 2007, twenty-three subjects at high risk for CIN (with an estimated glomerular filtration rate (eGFR)<50ml/min/1.73m(2)) undergoing diagnostic or therapeutic catheterization were treated with the system. The primary endpoint of the study was defined as the ability of the system to effectively dynamically match fluid administration to urine output. RESULTS: The 23 subjects at high risk for CIN enrolled had a mean±SD eGFR of 39±9.3. Patients achieved an hourly urine flow rate of 620±400ml/h. The system had a mean effectiveness rate of 99.9% over the duration of therapy with an average saline volume infused of 3825ml closely matched, minute to minute, to urine output of 3579ml. There were no major device-related complications from the experimental therapy, though one patient developed hypokalemia requiring replacement. Two subjects (9.5%) developed CIN as defined by >0.5mg/dl or >25% rise in serum creatinine at 48-60h post contrast administration when compared with the baseline. CONCLUSION: The study confirmed that the RenalGuard(TM) system is safe and dynamically balances volume hydration with urine production. Further randomized studies are needed to confirm the efficacy of the system in reducing the incidence of CIN.