A comprehensive overview of surgical and transcatheter therapies to treat tricuspid regurgitation in patients with heart failure.

PURPOSE OF REVIEW: The unique pathophysiologic considerations of severe tricuspid regurgitation (TR) have led to advancements in surgical and transcatheter treatments. The purpose of this review is to highlight the current surgical and transcatheter tricuspid valve interventions (TTVI) to functional TR. RECENT FINDINGS: Surgical repair with ring annuloplasty consistently demonstrates better outcomes than surgical replacement or other repair approaches. However, surgical uptake of TR correction remains relatively low, and operative mortality rates are still high owing to multiple comorbidities and advanced tricuspid valve disease/right ventricular dysfunction at time of referral. Pivotal trials for tricuspid transcatheter edge-to-edge repair (T-TEER) and transcatheter TV replacement (TTVR) indicate improved quality of life compared to medical therapy alone for high-surgical-risk patients with severe symptomatic TR. Trials are underway to assess caval valve implantation (CAVI), which holds hope for many severe TR patients who are not ideal candidates for T-TEER or orthotopic TTVR. Peri-procedural optimization of right ventricular function remains critical to promote both device success and patient outcomes. SUMMARY: Clinical outcomes after surgical TV intervention are poor, often due to intervening late in the disease course of TR. TTVI covers a treatment gap for patients deemed inoperable or high-surgical-risk, but earlier referral for TV interventions is still important prior to patients developing multiorgan dysfunction from chronic untreated TR.

Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proof-of-principle cohort study.

BACKGROUND: In patients with heart failure, interventions to reduce elevated left atrial pressure improve symptoms and reduce the risk of hospital admission. We aimed to assess the safety and potential efficacy of therapeutic left-to-right interatrial shunting in patients with heart failure with reduced ejection fraction. METHODS: We did this proof-of-principle cohort study at one centre in Canada. Patients (aged ≥18 years) with New York Heart Association (NYHA) class III chronic heart failure with reduced ejection fraction were enrolled under the Canadian special access programme. Shunt implants were done after transseptal catheterisation with transoesophageal echocardiographic guidance under general anaesthesia. Patients had clinical and echocardiography evaluations at baseline and months 1 and 3 after shunt implantation. FINDINGS: Between Oct 10, 2013, and March 27, 2015, we enrolled ten patients. The device was successfully implanted in all patients; no device-related or procedural adverse events occurred during follow-up. Transoesophageal echocardiography at 1 month showed that all shunts were patent, with no thrombosis or migration. From baseline to 3 month follow-up, we recorded improvements in NYHA classification (from class III to class II in seven [78%] of nine patients, from class III to class I in one [11%] patient, and no change in one [11%] patient; p=0·0004); quality of life, as assessed by the Duke Activity Status Index (from a mean score of 13 [SD 6·2] to 24·8 [12·9]; p=0·016) and the Kansas City Cardiomyopathy Questionnaire (from a mean score of 44·3 [SD 9·8] to 79·1 [13·0]; p=0·0001); and 6 min walk test distance (from a mean of 244 m [SD 112] to 318 m [134]; p=0·016). Pulmonary capillary wedge pressure was reduced from a mean of 23 mm Hg (SD 5) at baseline to 17 mm Hg (8) at 3 months (p=0·035), with no changes in right atrial pressure, pulmonary arterial pressure, or pulmonary resistance. No patient was admitted to hospital for worsening heart failure. One (10%) patient was admitted to hospital with gastrointestinal bleeding at month 1; one (10%) patient died after incessant ventricular tachycardia storm, which led to terminal heart failure 2 months post-procedure. INTERPRETATION: This first-in-man experience with an implanted left-to-right interatrial shunt demonstrates initial safety and early beneficial clinical and haemodynamic outcomes in patients with heart failure with reduced ejection fraction. Further large-scale randomised studies are warranted. FUNDING: V-Wave.

SYNERGY-Everolimus-Eluting Stent With a Bioabsorbable Polymer in ST-Elevation Myocardial Infarction: CLEAR SYNERGY OASIS-9 Registry.

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent (Boston Scientific Corporation, Marlborough, Massachusetts) in patients with ST-elevation myocardial infarction (STEMI). The only drug-eluting stent approved for treatment of STEMI by the Food and Drug Administration is the Taxus stent (Boston Scientific) which is no longer commercially available, so further data are needed. The CLEAR (Colchicine and spironolactone in patients with myocardial infarction) SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (n = 7,000), comparing colchicine versus placebo and spironolactone versus placebo. The primary outcome for the SYNERGY stent registry is major adverse cardiac events (MACE) as defined by cardiovascular death, recurrent MI, or unplanned ischemia-driven target vessel revascularization within 12 months. We estimated a MACE rate of 6.3% at 12 months after primary percutaneous coronary intervention for STEMI based on the Thrombectomy vs percutaneous coronary intervention alone in STEMI (TOTAL) trial. Success was defined as upper bound of confidence interval (CI) to be less than the performance goal of 9.45%. Overall, 733 patients were enrolled from 8 countries with a mean age 60 years, 19.4% diabetes mellitus, 41.3% anterior MI, and median door-to-balloon time of 72 minutes. The MACE rate was 4.8% (95% CI 3.2 to 6.3%) at 12 months which met the success criteria against performance goal of 9.45%. The rates of cardiovascular death, recurrent MI, or target vessel revascularization were 2.7%, 1.9%, 1.0%, respectively. The rates of acute definite stent thrombosis were 0.3%, subacute 0.4%, late 0.4%, and cumulative stent thrombosis of 1.1% at 12 months. In conclusion, the SYNERGY stent in STEMI performed well and was successful compared with the performance goal based on previous trials.

Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial.

AIMS: In heart failure (HF), implantable haemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided haemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure monitoring systems. We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients. METHODS AND RESULTS: The VECTOR-HF study (NCT03775161) was a first-in-human, prospective, multicentre, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After 3 months, a right heart catheterization was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute major adverse cardiac and neurological events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22 ± 4.92 mmHg, the correlation coefficient and the Lin's concordance correlation coefficient values were equal to 0.79 (p < 0.0001) and 0.776 (95% confidence interval 0.582-0.886), respectively. Preliminary experience with V-LAP-based HF management was associated with significant improvements in New York Heart Association (NYHA) functional class (32% of patients reached NYHA class II at 6 months, p < 0.005; 60% of patients at 12 months, p < 0.005) and 6-min walk test distance (from 244.59 ± 119.59 m at baseline to 311.78 ± 129.88 m after 6 months, p < 0.05, and 343.95 ± 146.15 m after 12 months, p < 0.05). CONCLUSION: The V-LAP™ monitoring system proved to be generally safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms.

Structural and Functional Evaluation of Coronary Arteries Treated With ABSORB Bioresorbable Vascular Scaffold at 5-Year Follow-Up.

Although complete bioresorbable vascular scaffold (BVS) resorption has been demonstrated at 5-year follow-up, whether corresponding vasomotor function restoration occurs remains unknown. The objective was to simultaneously assess the structural healing response along with vasomotor responses at 5-year follow-up of BVS implantation. We studied consecutive patients treated with ABSORB-BVS at 5-year follow-up (n = 31), who were recruited from a multicenter registry and were contacted to undergo a research protocol-driven repeat coronary angiogram involving intracoronary optical coherence tomography (OCT) and invasive coronary endothelial function testing. Epicardial endothelium-dependent vasomotion was defined as any vasodilatation after intracoronary acetylcholine (ACh), whereas endothelium-independent vasomotion was defined as any vasodilatation after intracoronary nitroglycerine (NTG), using quantitative coronary angiography. The mean implantation time point was 60.5 ± 4.6 months. OCT imaging demonstrated complete scaffold resorption in all patients. New coronary lesions (stenosis >50%) were found in 5 patients (16.1%), 3 of them underwent ad hoc percutaneous revascularization (9.7%). Intracoronary ACh (27 patients) and NTG testing (30 patients) was performed. Quantitative coronary angiography analysis demonstrated vasoconstriction after ACh administration and lack of response to NTG in BVS segments (mean lumen diameter = 2.00 ± 0.61 mm at baseline vs 1.74 ± 0.70 mm post-ACh, p <0.001; 2.05 ± 0.54 mm at baseline vs 2.03 ± 0.50 mm post-NTG, p = 0.69). OCT lumen analysis demonstrated similar vasoconstrictive responses to ACh (mean lumen area = 5.31 ± 2.26 mm2 at baseline vs 5.12 ± 2.55 mm2 post-ACh, p = 0.007) but had a vasodilatory response to NTG (5.96 ± 2.35 mm2 at baseline vs 6.17 ± 2.55 mm2 post-NTG, p<0.001). In conclusion, complete ABSORB-BVS resorption was demonstrated at 5-year follow-up. However, this healing response was associated with endothelium-dependent vasomotor dysfunction within the BVS segment.

Long-Term Intracoronary Structural and Vasomotor Assessment of the ABSORB Bioresorbable Vascular Scaffold.

We systematically categorized the longer-term (≥3 years) structural and functional characteristics of the ABSORB bioresorbable vascular scaffold (BVS) using optical coherence tomography imaging and coronary vasomotor reactivity testing and further compared the functional characteristics of BVS stented versus remote coronary segments. A total of 92 patients (mean age 56.4 ± 9.7 years, 22.8% women) who underwent percutaneous coronary intervention (76% with acute coronary syndrome) using the ABSORB BVS (112 lesions) were included. Optical coherence tomography analysis (38,790 visible struts) comprised in-segment quantitative lumen/plaque and semiquantitative plaque composition analysis of the neointimal pattern. Epicardial endothelium-dependent and-independent vasomotion was defined as any vasodilatation at low/intermediate intracoronary dose of acetylcholine (ACh) and nitroglycerine, assessed using quantitative coronary angiography. At a median time of 3.2 years follow-up, 79.8% of BVS segments still demonstrated visible struts with a predominant neointimal fibrotic healing pattern in 84% of BVS segments, with 99.5% of struts demonstrating coverage with apposition. Compared with remote segments, BVS segments demonstrated less endothelium-dependent vasodilatation at low (p = 0.06) and intermediate ACh doses (p = 0.04). Hypertension, longer time interval from index percutaneous coronary intervention, and the degree of in-BVS segment neointimal volume (p <0.03 for all) were each independently associated with abnormal BVS endothelium-dependent vasomotor function. Endothelium-independent function was more likely preserved in non-BVS (remote) segments compared with BVS segments (p = 0.06). In conclusion, at 3+ years post-ABSORB BVS insertion, the rate of complete scaffold resorption was low and residual strut presence was high, with a dominant fibrous healing response contributing toward neointimal hyperplasia and endothelium-dependent and-independent vasomotor dysfunction.

A new option for monitoring heart failure. First experience in Spain with CardioMEMS.

INTRODUCTION: The CardioMEMS device is inserted into the pulmonary artery and allows monitorization of pulmonary artery pressure in heart failure patients. Previous studies have shown a reduction in hospitalizations for heart failure and an improvement in quality of life in the group of patients monitored with the device. PATIENTS AND METHODS: Eleven patients managed in a multidisciplinary heart failure clinic implanted with the sensor were consecutively included from June 2019 to February 2020. This is the first experience with a cardioMEMS device published in Spain. RESULTS: The device was successfully implanted in all cases without severe complications or sensor failures, allowing precise adjustment of medical treatment that led to very few heart failure readmissions. DISCUSSION: Wireless pulmonary artery pressure monitoring will probably become an essential component in the management of selected HF patients.

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

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

Balancing the Risks of Thrombosis and Bleeding Following Transcatheter Aortic Valve Implantation: Current State-of-Evidence.

While transcatheter aortic valve implantation (TAVI) has rapidly evolved as an acceptable alternative to conventional surgical aortic valve replacement in elderly, high-risk surgical candidates with critical aortic stenosis, thrombotic and bleeding complications remain relatively frequent and potentially life-threatening. Thrombotic events during and following TAVI relate to the dynamic interplay between the systemic burden of atherosclerotic disease, atrial arrhythmias, device and native aortic valve interactions, as well as platelet and coagulation cascade activation. Bleeding in the acute setting relates primarily to access site vascular complications, but also appears related to pre-existing renal impairment and anemia. Current pre-, peri- and post-procedural anti-thrombotic regimens are empirical, based on expert consensus following extrapolation from the wealth of experience gleaned following percutaneous coronary intervention. However the complexities of the TAVI procedure, the high-risk clinical substrate and competing effects of anti-thrombotic regimens and bleeding risk are yet to be prospectively assessed in randomized clinical trials for defining evidence-based anti-thrombotic strategies.

Prognostic Value of Fat Mass and Skeletal Muscle Mass Determined by Computed Tomography in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Body composition (fat mass [FM] and skeletal muscle mass [SMM]) predicts clinical outcomes. In particular, loss of SMM (sarcopenia) is associated with frailty and mortality. There are no data on the prevalence and impact of FM and SMM in patients undergoing transcatheter aortic valve implantation (TAVI). The objective of this study is to determine body composition from pre-TAVI computed tomography (CT) and evaluate its association with clinical outcomes in patients who underwent TAVI. A total of 460 patients (mean age 81 ± 8 years, men: 51%) were included. Pre-TAVI CTs of the aorto-ilio-femoral axis were analyzed for FM and SMM cross-sectional area at the level of the third lumbar vertebrae (L3). Regression equations correlating cross-sectional area at L3 to total body FM and SMM were used to determine prevalence of sarcopenia, obesity, and sarcopenic obesity in patients (64%, 65%, and 46%, respectively). Most TAVI procedures were performed through a transfemoral approach (59%) using a balloon-expandable valve (94%). The 30-day and mid-term (median 12 months [interquartile range 6 to 27]) mortality rates were 6.1% and 29.6%, respectively. FM had no association with clinical outcomes, but sarcopenia predicted cumulative mortality (hazard ratio 1.55, 95% confidence interval 1.02 to 2.36, p = 0.04). In conclusion, body composition analysis from pre-TAVI CT is feasible. Sarcopenia, obesity, and sarcopenic obesity are prevalent in the TAVI population, with sarcopenia predictive of cumulative mortality.

Reducing periprocedural complications in transcatheter aortic valve replacement: review of paravalvular leaks, stroke and vascular complications.

Transcatheter aortic valve replacement has been established as the standard of care for inoperable patients and a valid alternative for high-risk individuals with severe symptomatic native aortic stenosis. Over the last decade, substantial improvement has been made in the transcatheter technology. Nevertheless, this less-invasive procedure is still associated with complications like paravalvular leaks, strokes and vascular complications. This review article discusses these worrisome complications associated with transcatheter aortic valve replacement and proposes methods to prevent these hurdles.

Transfemoral transcatheter aortic valve replacement compared with surgical replacement in patients with severe aortic stenosis and comparable risk: cost-utility and its determinants.

OBJECTIVE: To evaluate cost-effectiveness of transfemoral TAVR vs surgical replacement (SAVR) and its determinants in patients with severe symptomatic aortic stenosis and comparable risk. METHODS: Patients were prospectively recruited in 6 Spanish hospitals and followed up over one year. We estimated adjusted incremental cost-effectiveness ratio (ICER) (Euros per quality-adjusted life-year [QALY] gained) using a net-benefit approach and assessed the determinants of incremental net-benefit of TAVR vs SAVR. RESULTS: We analyzed data on 207 patients: 58, 87 and 62 in the Edwards SAPIEN (ES) TAVR, Medtronic-CoreValve (MC) TAVR and SAVR groups respectively. Average cost per patient of ES-TAVR was €8800 higher than SAVR and the gain in QALY was 0.036. The ICER was €148,525/QALY. The cost of MC-TAVR was €9729 higher than SAVR and the QALY difference was -0.011 (dominated). Results substantially changed in the following conditions: 1) in patients with high preoperative serum creatinine the ICERs were €18,302/QALY and €179,618/QALY for ES and MC-TAVR respectively; 2) a 30% reduction in the cost of TAVR devices decreased the ICER for ES-TAVR to €32,955/QALY; and 3) imputing hospitalization costs from other European countries leads to TAVR being dominant. CONCLUSIONS: In countries with relatively low health care costs TAVR is not likely to be cost-effective compared to SAVR in patients with intermediate risk for surgery, mainly because of the high cost of the valve compared to the cost of hospitalization. TAVR could be cost-effective in specific subgroups and in countries with higher hospitalization costs.

Dispositivos de protección embólica durante el TAVI: evidencias e incertidumbres actuales / Embolic protection devices during tavi: current evidence and uncertainties

El implante percutáneo de válvula aórtica (TAVI) es actualmente la principal opción terapéutica para los pacientes con estenosis aórtica grave considerados inoperables o de alto riesgo quirúrgico. La extensión de las indicaciones del TAVI a una población con un perfil de riesgo inferior puede verse limitada por las tasas relativamente altas de eventos cerebrovasculares asociados a la intervención. Estudios realizados con resonancia magnética cerebral con ponderación de difusión demuestran una alta incidencia de infartos cerebrales subclínicos de probable origen embólico tras el TAVI. Algunos estudios han relacionado estas lesiones con un deterioro cognitivo posterior. Los dispositivos de protección embólica nacen como una protección mecánica para impedir la embolización de partículas de material diverso hacia el cerebro durante la intervención. Se presenta una revisión de la evidencia y las incertidumbres existentes respecto a los tres dispositivos actuales (Embrella, TriGuard y Claret) diseñados específicamente para TAVI. Los estudios realizados tienen carácter exploratorio y evalúan el daño neurológico en tres aspectos: clínico, subclínico y cognitivo. El implante de los tres dispositivos parece viable y seguro. Por lo que respecta a la eficacia, ninguno ha mostrado una reducción significativa de las tasas de eventos clínicos. Sin embargo, los dispositivos Embrella y Claret han mostrado reducciones significativas del volumen total de lesión cerebral en las imágenes de resonancia magnética con ponderación de difusión. Los estudios que han evaluado los efectos en la capacidad cognitiva han mostrado resultados poco concluyentes. En conclusión, a pesar de que los dispositivos de protección embólica muestran reducciones del volumen total de lesión cerebral en la resonancia magnética con ponderación de difusión, la eficacia clínica en prevención del ictus/deterioro cognitivo deberá confirmarse en estudios más amplios (AU)

Transcatheter aortic valve implantation (TAVI) is now the principal therapeutic option in patients with severe aortic stenosis deemed inoperable or at high surgical risk. Implementing TAVI in a lower risk profile population could be limited by relatively high cerebrovascular event rates related to the procedure. Diffusion-weighted magnetic resonance imaging studies have demonstrated the ubiquitous presence of silent embolic cerebral infarcts after TAVI, with some data relating these lesions to subsequent cognitive decline. Embolic protection devices provide a mechanical barrier against debris embolizing to the brain during TAVI. We review the current evidence and ongoing uncertainties faced with the 3 currently available devices (Embrella, TriGuard and Claret) in TAVI. Studies evaluated neurological damage at 3 levels: clinical, subclinical, and cognitive. Feasibility and safety were analyzed for the 3 devices. In terms of efficacy, all studies were exploratory, but none demonstrated significant reductions in clinical event rates. The Embrella and Claret devices demonstrated significant reductions of the total cerebral lesion volume on diffusion-weighted magnetic resonance imaging. Studies evaluating the effects on cognition were also somewhat inconclusive. In conclusion, despite embolic protection devices demonstrating reductions in the total cerebral lesion volume on diffusion-weighted magnetic resonance imaging, the clinical efficacy in terms of preventing stroke/cognitive decline requires confirmation in larger studies (AU)

A new option for monitoring heart failure. First experience in Spain with CardioMEMS / Una nueva opción de monitorizar la insuficiencia cardiaca. Primera experiencia en España con CardioMEMS(TM)

INTRODUCTION: The CardioMEMS device is inserted into the pulmonary artery and allows monitorization of pulmonary artery pressure in heart failure patients. Previous studies have shown a reduction in hospitalizations for heart failure and an improvement in quality of life in the group of patients monitored with the device. PATIENTS AND METHODS: Eleven patients managed in a multidisciplinary heart failure clinic implanted with the sensor were consecutively included from June 2019 to February 2020. This is the first experience with a cardioMEMS device published in Spain. RESULTS: The device was successfully implanted in all cases without severe complications or sensor failures, allowing precise adjustment of medical treatment that led to very few heart failure readmissions. DISCUSSION: Wireless pulmonary artery pressure monitoring will probably become an essential component in the management of selected HF patients

INTRODUCCIÓN: El dispositivo CardioMEMS(TM) se inserta en la arteria pulmonar, y permite la monitorización de la presión arterial pulmonar en los pacientes con insuficiencia cardiaca. Los estudios previos han reflejado una reducción de las hospitalizaciones por insuficiencia cardiaca, así como una mejora de la calidad de vida en el grupo de pacientes monitorizados con el dispositivo. Pacientes and métodos: Se incluyó consecutivamente a 11 pacientes tratados en una clínica multidisciplinar para insuficiencia cardiaca, que tuvieron implantado el sensor de junio de 2019 a febrero de 2020. Esta es la primera experiencia con el dispositivo CardioMEMS(TM) que se publica en España. RESULTADOS: Se implantó exitosamente el dispositivo en todos los casos, sin complicaciones graves ni fallos del sensor, lo cual permitió el ajuste preciso del tratamiento médico, que redundó en pocos reingresos por insuficiencia cardiaca. DISCUSIÓN: La monitorización de la presión arterial pulmonar sin cables se convertirá probablemente en un componente esencial del tratamiento de los pacientes de insuficiencia cardiaca seleccionados