In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure.

AIMS: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). METHODS AND RESULTS: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. CONCLUSIONS: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Repeat Mitral Valve Interventions After Transcatheter Edge-to-Edge Repair: The COAPT Trial.

The frequency and effectiveness of repeat mitral valve interventions (RMVI) after transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) are unknown. We aimed to examine the rate of and outcomes after RMVI after TEER in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial. Only 3.9% of COAPT trial patients required a repeat mitral valve intervention during 4-year follow-up which was successful in 90% of cases but was associated with an increased rate of heart failure (HF) hospitalizations (HFH). The COAPT trial randomized HF patients with severe secondary MR to TEER with the MitraClip device plus guideline-directed medical therapy (GDMT) versus GDMT alone. We evaluated the characteristics and outcomes of patients who had an RMVI during 4-year follow-up. A MitraClip implant was attempted in 293 patients randomized to TEER+GDMT, 10 of whom underwent an RMVI procedure (9 repeat TEER and 1 surgical mitral valve replacement) after 4 years of follow-up (cumulative incidence 3.90%, 95% confidence interval [CI] 2.08 to 7.08; median 182 days after the initial procedure). Patients with RMVI had larger mitral annular diameters, fewer clips implanted, and were more likely to have ≥3+MR at discharge compared with those without RMVI. Reasons for RMVI included failed index procedure because of difficult transseptal puncture (n = 2) or tamponade (n = 1); residual or recurrent severe MR after an initially successful procedure (n = 5); partial clip detachment (n = 1); and site-assessed mitral stenosis (n = 1). RMVI was successful in 8/10 (80%) patients. Patients who underwent RMVI had higher 4-year rates of HFH but similar mortality compared with those without RMVI. The annualized incidence rates of all HFH in patients who underwent RMVI were 234 events per 100 person-years (95% CI 139 to 395) pre-RMVI and 46 per 100 person-years (95% CI 25 to 86) post-RMVI as compared with 32 events per 100 patient-years (95% CI 28 to 36) in patients without RMVI. The rate ratio of HFH was reduced after RMVI in patients who underwent RMVI (0.20, 95% CI 0.09 to 0.45). In conclusion, the cumulative incidence of RMVI after 4 years was 3.9% in patients who underwent TEER for severe secondary MR in the COAPT trial. Patients who underwent RMVI were at increased risk of HFH which was reduced after the RMVI procedure. Clinical Trial Registration: Clinical Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL:https://clinicaltrials.gov/ct2/show/NCT01626079.

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.

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.

Tricuspid Regurgitation Management for Heart Failure.

There is growing evidence that severe tricuspid regurgitation (TR) impacts clinical outcomes in a variety of cardiovascular disease states. The late presentation of patients with advanced TR highlights the underappreciation of the disease, as well as the pitfalls of current guideline-directed medical management. Given the high in-hospital mortality associated with isolated tricuspid valve surgery, transcatheter options continue to be explored with the hope of improved survival and reduced heart failure hospitalizations. In this review, we explore the physiology of TR, discuss the etiologic classes of TR, and explore the transcatheter options for treatment and who might benefit from device therapy.

Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository.

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII. Paired serum samples were obtained in 140 patients before implantation and at 90 days postimplantation. Baseline demographics were as follows: age 57 ± 13 years, 41% had ischemic etiology, 82% male, and 75% destination therapy indication. In the 17 patients with baseline elevation of both TNF-α and Ang-2, 10 (60%) experienced a significant bleeding event within 180 days postimplant compared with 37 of 98 (38%) patients with Ang-2 and TNF-α below the mean ( p = 0.02). The hazard ratio for a bleeding event was 2.3 (95% CI: 1.2-4.6) in patients with elevated levels of both TNF-α and Ang-2. In the PREVENT multicenter study, patients with elevations in serum Angiopoietin-2 and TNF-α at baseline before LVAD implantation demonstrated increased bleeding events after LVAD implantation.

Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial.

BACKGROUND: The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined. OBJECTIVES: The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression. RESULTS: The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m2 decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (Pinteraction = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months. CONCLUSIONS: In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).

Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement Outcomes in Left Ventricular Assist Device Patients with Aortic Insufficiency.

Background: Worsening aortic insufficiency (AI) is a known sequela of prolonged continuous-flow left ventricular assist device (LVAD) support with a significant impact on patient outcomes. While medical treatment may relieve symptoms, it is unlikely to halt progression. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are among non-medical interventions available to address post-LVAD AI. Limited data are available on outcomes with either SAVR or TAVR for the management of post-LVAD AI. Methods: The National Inpatient Sample data collected for hospital admissions between the years 2015 and 2018 for patients with pre-existing continuous-flow LVAD undergoing TAVR or SAVR for AI were queried. The primary outcome of interest was a composite of in-hospital mortality, stroke, transient ischaemic attack, MI, pacemaker implantation, need for open aortic valve surgery, vascular complications and cardiac tamponade. Results: Patients undergoing TAVR were more likely to receive their procedure during an elective admission (57.1 versus 30%, p=0.002), and a significantly higher prevalence of comorbidities, as assessed by the Elixhauser Comorbidity Index, was observed in the SAVR group (29 versus 18; p=0.0001). We observed a significantly higher prevalence of the primary composite outcome in patients undergoing SAVR (30%) compared with TAVR (14.3%; p=0.001). Upon multivariable analysis adjusting for the type of admission and Elixhauser Comorbidity Index, TAVR was associated with significantly lower odds of the composite outcome (odds ratio 0.243; 95% CI [0.06-0.97]; p=0.045). Conclusion: In this nationally representative cohort of LVAD patients with post-implant AI, it was observed that TAVR was associated with a lower risk of adverse short-term outcomes compared with SAVR.

Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation and the growing interest in donation after circulatory death (DCD), our institution recently began procuring cardiac allografts from DCD donors. METHODS: Between October 2020 and March 2021, 15 patients with heart failure underwent cardiac transplantation using DCD allografts. Allografts were procured using a modified extracorporeal membrane oxygenation circuit for thoracic normothermic regional perfusion (TA-NRP) and were subsequently transported using cold static storage. Data collection and analysis were performed with institutional review board approval. RESULTS: The mean age of the DCD donors was 23 ± 7 years and average time on TA-NRP was 56 ± 8 minutes. Total ischemic time was 183 ± 31 minutes and distance from transplant center was 373 ± 203 nautical miles. Recipient age was 55 ± 14 years, with 8 (55.3%) recipients on durable left ventricular assist device support. Post-transplant, 6 (40%) recipients experienced mild left ventricle primary graft dysfunction (PGD-LV), 3 (20%) recipients experienced moderate PGD-LV, and no recipients experienced severe PGD-LV. Postoperative transthoracic echocardiogram demonstrated left ventricular ejection fraction >55% in all recipients. One recipient (6.6%) developed International Society for Heart and Lung Transplantation 2R acute cellular rejection on first biopsy. At last follow-up, all 15 recipients were alive past 30-days. CONCLUSIONS: Cardiac DCD provides an opportunity to increase the availability of donor hearts for transplantation. Utilizing TA-NRP with cold static storage, we have extended the cold ischemic time of DCD allografts to almost 3 hours, allowing for inter-hospital organ transport.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Variants in mycophenolate and CMV antiviral drug pharmacokinetic and pharmacodynamic genes and leukopenia in heart transplant recipients.

BACKGROUND: The objective was to assess the relationship between single nucleotide polymorphisms in mycophenolate and cytomegalovirus antiviral drug pharmacokinetic and pharmacodynamic genes and drug-induced leukopenia in adult heart transplant recipients. METHODS: This retrospective analysis included n = 148 patients receiving mycophenolate and a cytomegalovirus antiviral drug. In total, 81 single nucleotide polymorphisms in 21 pharmacokinetic and 23 pharmacodynamic genes were selected for investigation. The primary and secondary outcomes were mycophenolate and/or cytomegalovirus antiviral drug-induced leukopenia, defined as a white blood cell count <3.0 × 109/L, in the first six and 12 months post-heart transplant, respectively. RESULTS: Mycophenolate and/or cytomegalovirus antiviral drug-induced leukopenia occurred in 20.3% of patients. HNF1A rs1169288 A>C (p.I27L) was associated with drug-induced leukopenia (unadjusted p = 0.002; false discovery rate <20%) in the first six months post-transplant. After adjusting for covariates, HNF1A rs1169288 variant C allele carriers had significantly higher odds of leukopenia compared to A/A homozygotes (odds ratio 6.19; 95% CI 1.97-19.43; p = 0.002). Single nucleotide polymorphisms in HNF1A, SLC13A1, and MBOAT1 were suggestively associated (p < 0.05) with the secondary outcome but were not significant after adjusting for multiple comparisons. CONCLUSION: Our data suggest genetic variation may play a role in the development of leukopenia in patients receiving mycophenolate and cytomegalovirus antiviral drugs after heart transplantation. Following replication, pharmacogenetic markers, such as HNF1A rs1169288, could help identify patients at higher risk of drug-induced leukopenia, allowing for more personalized immunosuppressant therapy and cytomegalovirus prophylaxis following heart transplantation.

Prioritizing heart transplantation during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program. METHODS: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival. RESULTS: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029). CONCLUSION: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

Percutaneous Mitral Valve Annuloplasty in Patients With Secondary Mitral Regurgitation and Severe Left Ventricular Enlargement.

OBJECTIVES: This study sought to determine the effect of percutaneous mitral valve annuloplasty with the Carillon device versus guideline-directed medical therapy (GDMT) alone in patients with secondary mitral regurgitation (MR) and severe left ventricular (LV) enlargement. BACKGROUND: The clinical impact of the Carillon device in patients with severe LV dilation is not well established. METHODS: This is a pooled analysis involving 3 prospective trials (TITAN [Transcatheter Implantation of Carillon Mitral Annuloplasty Device], TITAN II, and REDUCE FMR [CARILLON Mitral Contour System for Reducing Functional Mitral Regurgitation] trials) in which patients with functional MR and severe LV enlargement (LV end-diastolic diameter >65 mm) were treated with GDMT and the Carillon device versus GDMT alone. Key outcomes of this analysis were changes over 1 year of follow-up in mitral valve and LV echocardiographic parameters, functional outcome, quality of life, mortality, and heart failure hospitalization (HFH). RESULTS: A total of 95 patients (67 in the Carillon group, 28 in the GDMT group) with severe LV enlargement were included. In the Carillon group, all mitral valve and LV morphology parameters were significantly improved at 1 year. Regurgitant volume decreased by 12 ml (p < 0.001), MR grade decreased by 0.6 U (p < 0.001), LV end-diastolic volume decreased by 25 cm3 (p = 0.005), and LV end-systolic volume decreased by 21 cm3 (p = 0.01). Significant functional improvement differences were also noted between the Carillon group and the GDMT group including an improvement of Kansas City Cardiomyopathy Questionnaire score (15 ± 4 vs. 6 ± 6; p = 0.03). The incidence of HFH was 29.9% versus 50.0% and the cumulative rate of HFH was 0.43 versus 0.75 (p < 0.001). CONCLUSIONS: In patients with functional MR and severe LV enlargement, the Carillon device improved mitral valve function, LV morphology, and functional outcome compared with patients receiving GDMT only. Preoperative LV dimension should not be a limiting factor when evaluating patient eligibility or anticipated response to therapy with the Carillon device.

Impact of tricuspid regurgitation on survival in patients with heart failure: a large electronic health record patient-level database analysis.

AIMS: More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). METHODS AND RESULTS: Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. CONCLUSIONS: In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.