Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study.

BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.

Transcatheter transseptal treatment of patients with severe mitral regurgitation using an atrial fixation mitral valve replacement technology.

BACKGROUND: Mitral regurgitation (MR) is the most common valvular heart disease worldwide with a 5-year mortality rate of 50 % with medical therapy alone. Several transcatheter mitral valve replacement (TMVR) devices are being investigated in clinical trials. Early evidence has demonstrated clinical benefits with a reduction in heart failure symptoms, low rates of residual MR, and reverse remodeling of the left ventricle (LV) over time. However, high anatomical screen failure rates limit its applicability. The primary reasons for the anatomical screen failure are risk of LV outflow tract obstruction, large mitral valve annulus size, and the presence of mitral annular calcification. Our clinical experiences using an atrial only fixation TMVR technology delivered via a transfemoral-transseptal approach is described. METHODS: Three consecutive patients with severe functional MR underwent TMVR implantation using an atrial only fixation technology and a low-profile transseptal delivery system. RESULTS: Technical success was achieved in 100 % of the patients with a clinically significant reduction in MR. Longer-term follow-up (up to 6-months) has demonstrated a sustained reduction in MR and significant improvement in quality of life for all patients. CONCLUSIONS: Longer-term outcomes in our patients showed persistent reduction in MR, sustained implant performance, and notable improvements in NYHA Class and quality of life. There were no major adverse events. Follow-up CT data showed no evidence of device-related thrombosis, with stable valve position and integrity. The atrial fixation TMVR technology may have benefits in preserving the dynamics of the native mitral valve annulus thereby reducing the overall risk of LVOT obstruction. SHORT ABSTRACT: We present a single-center experience of three consecutive patients with severe functional MR treated with the AltaValve using a low-profile transseptal delivery system. A clinically significant reduction in mitral regurgitation was achieved in all patients, and longer-term follow-up has demonstrated sustained clinical benefits.

The Hemodynamic Effects of Aortic Regurgitation in Patients Supported by a HeartMate 3 Left Ventricular Assist Device.

BACKGROUND: Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. METHODS AND RESULTS: Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). CONCLUSIONS: In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.

Imaging Methods for Evaluation of Chronic Aortic Regurgitation in Adults: JACC State-of-the-Art Review.

A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation.

Transfemoral Transcatheter Mitral Valve Implantation With a Dedicated Device in a Rheumatic Mitral Stenosis Patient.

A 65-year-old obese woman with rheumatic heart disease and restrictive lung disease presented with decompensated heart failure. Evaluation demonstrated severely thickened mitral valve leaflets, severe mitral stenosis, and moderate mitral regurgitation. She underwent successful transfemoral transseptal transcatheter mitral valve replacement with a dedicated valve resulting in improved functional status. (Level of Difficulty: Advanced.).

Flexible-Interval High-Sensitivity Troponin Velocity for the Detection of Acute Coronary Syndromes.

Many algorithms for emergency department (ED) evaluation of acute coronary syndrome (ACS) using high-sensitivity troponin assays rely on the detection of a "delta," the difference in concentration over a predetermined interval, but collecting specimens at specific times can be difficult in the ED. We evaluate the use of troponin "velocity," the rate of change of troponin concentration over a flexible short interval for the prediction of major adverse cardiac events (MACEs) at 30 days. We conducted a prospective, observational study on a convenience sample of 821 patients who underwent ACS evaluation at a high-volume, urban ED. We determined the diagnostic performance of a novel velocity-based algorithm and compared the performance of 1- and 2-hour algorithms adapted from the European Society of Cardiology (ESC) using delta versus velocity. A total of 7 of 332 patients (2.1%) classified as low risk by the velocity-based algorithm experienced a MACE by 30 days compared with 35 of 221 (13.8%) of patients classified as greater than low risk, yielding a sensitivity of 83.3% (95% confidence interval [CI] 68.6% to 93.0%) and negative predictive value (NPV) of 97.9% (95% CI 95.9% to 98.9%). The ESC-derived algorithms using delta or velocity had NPVs ranging from 98.4% (95% CI 96.4% to 99.3%) to 99.6% (95% CI 97.0% to 99.9%) for 30-day MACEs. The NPV of the novel velocity-based algorithm for MACE at 30 days was borderline, but the substitution of troponin velocity for delta in the framework of the ESC algorithms performed well. In conclusion, specimen collection within strict time intervals may not be necessary for rapid evaluation of ACS with high-sensitivity troponin.

The Case for Inclusion of a Lipid Panel in the Standard Precatheterization Laboratory Blood Draw-Stating What Should Be Obvious.

This Viewpoint describes the advantages of measuring a lipid panel before cardiac catheterization to optimize lipid-lowering therapy.

Cardiac Computed Tomography Angiography Anatomical Characterization of Patients Screened for a Dedicated Transfemoral Transcatheter Valve System for Primary Aortic Regurgitation.

Background: Cardiac computed tomography angiography was used to identify anatomical characteristics of the aortic root in patients with severe aortic regurgitation (AR) as compared to those with aortic stenosis (AS) to judge feasibility of transcatheter aortic valve replacement (TAVR) with the JenaValve Trilogy system. Methods: Cardiac computed tomography angiography was performed prior to planned TAVR for 107 patients with severe AR and 92 patients with severe AS. Measurements related to aortic root and coronary artery anatomy were obtained and compared between groups. Perimeter >90 mm and aortic annulus angle â€‹>70 degrees were defined as the theoretical exclusion criteria for TAVR. A combination of sinus of Valsalva diameter <30 mm and coronary height <12 mm was defined as high risk for coronary occlusion. Results: The mean age of patients in the AR group was 74.9 ± 11.2 years, 46% were women, and the mean Society of Thoracic Surgeons risk score for mortality was 3.6 ± 2.1. Comparatively, the mean age of patients in the AS group was 82.3 ± 5.53 years, 65% were women, and the mean Society of Thoracic Surgeonsrisk score was 5.5 ± 3.3. Annulus area, perimeter, diameter, and angle were larger in patients with severe AR. Sinus of Valsalva diameters and heights were larger in patients with severe AR. More AR patients were excluded based on perimeter (14 vs. 2%) and annulus angle (6 vs. 1%). More AS patients exhibited high-risk anatomy for left main coronary occlusion (21 vs. 7%) and right coronary occlusion (14 vs. 3%). The maximum dimension of the ascending aorta was larger in patients with severe AR (39 vs. 35 mm). The percentage of referred AR patients with significant aortopathy requiring surgical intervention was very low (only 1 AR patient with ascending aorta diameter >5.5 cm). Conclusions: A significantly larger proportion of patients with severe AR are excluded from TAVR as compared to AS due to large aortic annulus size and steep annulus angulation. By far the most prevalent excluding factor is aortic annulus size, with fewer patients excluded due to angulation. AR patients have lower-risk anatomy for coronary occlusion. Larger transcatheter valve sizes and further delivery system modifications are required to treat a larger proportion of AR patients.

Zero-Contrast Left Atrial Appendage Occlusion Using a Hybrid Echocardiography-Fluoroscopy Technique Without Iodinated Contrast.

Contrast exposure during left atrial appendage occlusion may be harmful in those with chronic kidney disease or allergy. This single-center registry (n = 31) demonstrates the feasibility and safety of zero-contrast percutaneous left atrial appendage occlusion using echocardiography, fluoroscopy, and fusion imaging, with 100% procedural success and no device complications at 45 days.

Impact of a rapid high-sensitivity troponin pathway on patient flow in an urban emergency department.

Study Objective: To evaluate whether the introduction of a 1-hour high-sensitivity cardiac troponin-T (hs-TnT) pathway for patients who present to the emergency department (ED) with suspected acute coronary syndrome (ACS) improves ED patient flow without changing the rate of "missed" major adverse cardiac events (MACE), compared to use of conventional cardiac troponin with an associated 3-hour pathway. Methods: This was a prospective, uncontrolled observational study conducted before and after implementation of a 1-hour hs-TnT pathway at a high-volume urban ED. Patients undergoing evaluation for ACS in the ED were enrolled during their initial visit and clinical outcomes were assessed at 30 and 90 days. Throughput markers were extracted from the electronic medical record and compared. The primary outcome was provider-to-disposition decision time. Results: A total of 1892 patients were enrolled, 1071 patients while using conventional troponin and 821 after introduction of hs-TnT. With the new assay and pathway, median interval between troponin tests decreased from 4.7 hours (interquartile range [IQR] 3.9-5.7 hours) to 2.3 hours (IQR 1.5-3.4 hours) (P < 0.001). However, there was no difference in median provider-to-disposition decision time, which measured 4.7 hours (IQR 2.9-7.2) and 4.8 hours (IQR 3.1-7.1) (P = 0.428) respectively. Total 30-day MACE rate in discharged patients was low in both groups, occurring in only 4/472 (0.85%) encounters in the first cohort and 4/381 (1.0%) encounters in the second. Conclusion: Introduction of a 1-hour hs-TnT ACS evaluation pathway reduced the troponin collection interval but did not reduce provider to disposition time. There was no difference in rate of 30-day MACE in patients discharged from the ED.

An Unusual Cause of Shortness of Breath: Pulmonary Vein Stenosis After Surgical Mitral Valve Replacement.

A 79-year-old man with prior bioprosthetic mitral valve replacement presented with progressive shortness of breath and was found to have right upper pulmonary vein stenosis and paravalvular leak diagnosed with the use of multimodal imaging. The patient underwent balloon angioplasty, stenting of the pulmonary vein, and paravalvular leak closure with ultimate resolution of symptoms. (Level of Difficulty: Intermediate.).

Impact of inferior vena cava entry characteristics on tricuspid annular access during transcatheter interventions.

OBJECTIVES: The purpose of this study was to characterize the anatomic relationship between the inferior vena cava (IVC) and tricuspid annulus (TA) and its potential impact on the performance of transcatheter TV interventions. BACKGROUND: Transcatheter tricuspid valve (TV) interventions are emerging as a therapeutic alternative for the treatment of severe, symptomatic tricuspid regurgitation (TR). Progression of TR is associated with right heart dilatation. These anatomic changes may distort the IVC-TA relationship and impact successful implantation of transcatheter devices. METHODS: Fifty patients who presented with symptomatic TR for consideration of transcatheter TV therapy with an available CT were included in the study. Comprehensive transesophageal echocardiogram and CT analyses were performed to assess the right-sided cardiac chambers, TA and IVC-TA relationship. RESULTS: The mean age of the study cohort was 78.4 ± 8.9 years. Torrential TR was present in 54% (n = 27). There was considerable variation in the short axis mid-IVC to mid-TA offset (SAXMID 18.2 ± 7.9 mm, range 4.7-42.1 mm). CONCLUSIONS: The IVC-to-TA relationship exhibits significant variability in patients with symptomatic TR. CT analysis of the tricuspid anatomy, including the relationship to the surrounding structures and the IVC, is essential for planning transcatheter TV interventions. Further studies are needed to define whether the IVC-to-TA relationship is a predictor of technical success in the context of specific transcatheter delivery systems.

Comparison of Risk Models in the Prediction of 30-Day Mortality in Acute Myocardial Infarction-Associated Cardiogenic Shock.

Background: There are numerous risk-prediction models applied to acute myocardial infarction-related cardiogenic shock (AMI-CS) patients to determine a more accurate prognosis and to assist in patient triage. There is wide heterogeneity among the risk models including the nature of predictors evaluated and their specific outcome measures. The aim of this analysis was to evaluate the performance of 20 risk-prediction models in AMI-CS patients. Methods: Patients included in our analysis were admitted to a tertiary care cardiac intensive care unit with AMI-CS. Twenty risk-prediction models were computed utilizing vitals assessments, laboratory investigations, hemodynamic markers, and vasopressor, inotropic and mechanical circulatory support available from within the first 24 â€‹hours of presentation. Receiver operating characteristic curves were used to assess the prediction of 30-day mortality. Calibration was assessed with a Hosmer-Lemeshow test. Results: Seventy patients (median age 63 years, 67% male) were admitted between 2017 and 2021. The models' area under the curve (AUC) ranged from 0.49 to 0.79, with the Simplified Acute Physiology Score II score having the most optimal discrimination of 30-day mortality (AUC: 0.79, 95% confidence interval [CI]: 0.67-0.90), followed by the Acute Physiology and Chronic Health Evaluation-III score (AUC: 0.72, 95% CI: 0.59-0.84) and the Acute Physiology and Chronic Health Evaluation-II score (AUC: 0.67, 95% CI: 0.55-0.80). All 20 risk scores demonstrated adequate calibration (p > 0.05 for all). Conclusions: Among the models tested in a data set of patients admitted with AMI-CS, the Simplified Acute Physiology Score II risk score model demonstrated the highest prognostic accuracy. Further investigations are required to improve the discriminative capabilities of these models or to establish new, more streamlined and accurate methods for mortality prognostication in AMI-CS.

First Transfemoral Implantation of a Novel Transcatheter Valve in an LVAD Patient With Aortic Insufficiency.

An 80-year-old man with a destination left ventricular assist device (LVAD) presented with decompensated heart failure. Evaluation demonstrated numerous LVAD high power spike events, significant aortic regurgitation, and hemolysis. He underwent successful aortic valve replacement with a novel transcatheter valve and LVAD pump exchange that resulted in an improvement in his clinical status. (Level of Difficulty: Advanced.).