Interatrial Shunt Device Research Articles

InterAtrial Shunt Device in diastolic heart failure

All types of heart failure are associated with reduced cardiac output and/or increased left atrial (LA) pressure. In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the increased LA pressure plays a central role, leading to pulmonary venous hypertension (PVH) and increased pulmonary artery pressure. These pressure parameters are presumably decisive for the symptoms and mortally of heart failure, particularly of the diastolic form. This is the basis for treatment with an interarterial shunt to reduce LA pressure in patients with diastolic heart failure and PVH. At first glance, this appears paradoxical, since closure of an atrial septum defect serves to prevent increased pulmonary vascular resistance and paradoxical embolism. Prevention of increased pulmonary vascular resistance and paradoxical embolism is thus an essential aspect in the development of devices for establishing an interarterial shunt. Reports on the InterAtrial Shunt Device (IASD®) and the V‑Wave have been published, both of which can be implanted with a low risk and few complications. The V‑Wave device is equipped with a valve to prevent paradoxical embolisms. However, paradoxical embolisms were also not observed with the IASD®, and the valve of the V‑Wave exhibited considerable degenerative changes and valve closure. Hemodynamic and clinical data of patients with an IASD® or an open V‑Wave device demonstrated asustained hemodynamic improvement. Physical performance capacity and quality of life were increased. Whether IASD® may be broadly applicable in patients with diastolic heart failure is currently under investigation. In selected highly symptomatic patients with diastolic heart failure and PVH, the IASD® is already in clinal use.

One-Year Safety and Clinical Outcomes of a Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction in the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (REDUCE LAP-HF I) Trial

In patients with heart failure (HF) and left ventricular ejection fraction (LVEF) equal to or greater than 40%, a transcatheter interatrial shunt device (IASD; Corvia Medical) reduces exercise pulmonary capillary wedge pressure (PCWP) and is safe compared with sham control treatment at 1 month of follow-up. The longer-term safety and patency of the IASD has not yet been demonstrated in the setting of a randomized clinical trial (RCT). To evaluate the 1-year safety and clinical outcomes of the IASD compared with a sham control treatment. This phase 2, double-blind, 1-to-1 sham-controlled multicenter RCT of IASD implantation vs a sham procedure (femoral venous access and imaging of the interatrial septum without IASD) was conducted in 22 centers in the United States, Europe, and Australia on patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, LVEF equal to or greater than 40%, exercise PCWP equal to or greater than 25 mm Hg, and PCWP-right atrial pressure gradient equal to or greater than 5 mm Hg. Safety was assessed by major adverse cardiac, cerebrovascular, or renal events (MACCRE). Exploratory outcomes evaluated at 1 year were hospitalizations for HF, NYHA class, quality of life, a 6-minute walk test, and device patency. After 1 year, shunts were patent in all IASD-treated patients; MACCRE did not differ significantly in the IASD arm (2 of 21 [9.5%]) vs the control arm (5 of 22 [22.7%]; P = .41), and no strokes occurred. The yearly rate of hospitalizations for HF was 0.22 in the IASD arm and 0.63 in the control arm (P = .06). Median improvement in NYHA class was 1 class in the IASD arm (IQR, -1 to 0) vs 0 in the control arm (IQR, -1 to 0; P = .08). Quality of life and 6-minute walk test distance were similar in both groups. At 6 months, there was an increase in right ventricular size in the IASD arm (mean [SD], 7.9 [8.0] mL/m2) vs the control arm (-1.8 [9.6] mL/m2; P = .002), consistent with left-to-right shunting through the device; no further increase occurred in the IASD arm at 12 months. The REDUCE LAP-HF I phase 2, sham-controlled RCT confirms the longer-term patency of the IASD. Through 1 year of follow-up, IASD treatment appears safe, with no significant differences in MACCRE in patients receiving IASD compared with those who received sham control treatment. ClinicalTrials.gov identifier: NCT02600234.

Impact of Baseline Hemodynamics on the Effects of a Transcatheter Interatrial Shunt Device in Heart Failure With Preserved Ejection Fraction

Background Interatrial shunt device (IASD) effects have been described in patients with heart failure and ejection fractions (EFs) ≥40%. However, baseline characteristics that correlate with greatest hemodynamic effects are unknown. On the basis of fundamental principles, we hypothesized that larger pressure gradients between left and right atria would yield greater shunt flow and greater hemodynamic effects. Methods and Results REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a multicenter study that investigated IASD safety and performance. Sixty-four patients with EF ≥40% underwent device implantation followed by hemodynamic assessments at rest and exercise, including pulmonary capillary wedge pressure (PCWP, surrogate for left atrial pressure) and central venous pressure (CVP). At 6 months, IASD resulted in an average pulmonary-to-systemic blood flow ratio of 1.27 and increased exercise tolerance. The PCWP-CVP gradient (ie, the driving pressure for shunt flow) decreased at peak exercise from 16.8±6.9 to 11.4±5.5 mm Hg, because of increased CVP (17.5±5.4 to 20.3±7.9 mm Hg; P=0.04) and decreased PCWP (34.1±7.6 to 31.6±8.0 mm Hg; P=0.025). Baseline PCWP-CVP gradient during exercise correlated with changes of both PCWP-CVP and PCWP: Δ(PCWP-CVP)=10.0-0.89·(PCWP-CVP)baseline ( r2=0.56) and ΔPCWP=7.54-0.60·(PCWP-CVP)baseline ( P=0.001). Hemodynamics of patients with EF ≥50% and those with EF <50% responded similarly to IASD. Conclusions In heart failure patients with EF ≥40%, IASD significantly reduced PCWP and PCWP-CVP at peak exercise. Patients with higher baseline PCWP-CVP gradient had greater reductions in both parameters at follow-up. Results were sustained through 12 months and were independent of whether EF was ≥50% or between 40% and 49%. Additional studies will help further define the baseline hemodynamic predictors of exercise, hemodynamic, and clinical efficacy of the IASD. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01913613.

Device therapy: Interatrial shunt device for HFpEF.

Device therapy: Interatrial shunt device for HFpEF.

Interatrial shunt devices for heart failure with normal ejection fraction: a technology update.

Heart failure with normal ejection fraction (HeFNEF) accounts for ~50% of heart failure admissions. Its pathophysiology and diagnostic criteria are yet to be defined clearly which may hinder the search for effective treatments. The clinical hallmark of HeFNEF is exertional breathlessness, often due to an abnormal increase in left atrial pressure during exercise. Creation of an interatrial communication to offload the left atrium is a possible therapeutic approach. There are two percutaneously delivered devices currently under investigation which are discussed in this review.

Efficacy and Safety of Inter-Atrial Shunt Devices for Heart Failure With Reduced or Preserved Ejection Fraction: Early Experiences

Elevated left atrial (LA) pressure is thought to be the common final pathological way in decompensated heart failure (HF). We aimed to gather currently available clinical evidence to evaluate the feasibility of inter-atrial shunt devices in HF patients. We searched PubMed and Cochrane Library databases through 23rd April 23, 2016. Data were extracted by two investigators independently. We pooled outcomes of interest in Revman 5.2 (The Cochrane Collaboration, Oxford, United Kingdom). A total of four records were identified in the final review, involving HF patients with reduced ejection fraction (EF) and those with preserved EF. Pooled analysis showed that pulmonary capillary wedge pressure significantly reduced after inter-atrial shunt devices implantation, with a mean difference (MD) of -3.54mmHg (95% confidence interval [CI]=-5.63 to -1.45mmHg) and low heterogeneity (I2=16%), 6-minute walk distance significantly increased, with a MD of 36.84m (95% CI=3.52 to 70.16m) and low heterogeneity (I2=0%), and Minnesota Living with Heart Failure score significantly improved (MD=-22.99 with 95% CI -44.45 to -1.52) following shunting. No evidence of worsening pulmonary hypertension was observed in these studies. No device-related deaths, thrombo-embolic or cardiac events were recorded during follow-up. Current evidence suggests that inter-atrial shunting might be a potential and promising therapy for HF, regardless of the ejection fraction.

Cardiac Unloading with an Implantable Interatrial Shunt in Heart Failure: Serial Observations in an Ovine Model of Ischemic Cardiomyopathy

ABSTRACTBackground: Patients with dilated cardiomyopathy often have progressive heart failure with systolic dysfunction, ventricular remodeling and clinical decompensation heralded by elevations of filling pressures. Our hypothesis is that an interatrial shunt device can regulate left atrial pressure and stabilize left ventricular function without overloading the right heart.Methods: Sheep (N = 21) were subjected to repeat coronary microembolization until left ventricular dysfunction with reduced LVEF was documented. After study group assignment, animals were chronically instrumented during thoracotomy. Shunts were implanted in n = 14 and n = 7 were sham controls. Hemodynamic and echocardiographic responses were serially evaluated for 12 weeks.Results: Comparisons at study termination showed improved outcomes with interatrial shunting (LVEF 46 ± 11% vs. 18 ± 3%; fractional shortening 19 ± 6% vs. 6 ± 1%; ventricular septal thickness 1.2 ± 0.2 cm vs. 1.0 ± 0.3 cm; left atrial pressure 14 ± 3 mmHg vs. 25 ± 5 mmHg; mean pulmonary artery pressure 24 ± 4 mmHg vs. 37 ± 8 mmHg; right atrial pressure 8 ± 4 mmHg vs. 15 ± 4 mmHg; LV dP/dtmax 1515 ± 391 mmHg·s−1 vs. 879 ± 333 mmHg−s−1; LV dP/dtmin −2116 ± 569 mmHg·s−1 vs. −1138 ± 545 mmHg·s−1; p ≤ 0.03 for all comparisons). These findings were supported by gross pathological observations and there was a survival advantage with shunting (13/14 vs. 4/7 at 12 weeks, p = 0.047). Shunts were small with Qp:Qs 1.2 ± 0.1 and all devices were patent at necropsy.Conclusion: In an animal model of ischemic cardiomyopathy, interatrial shunting selectively unloaded the left-heart leading to sustained reductions in left-atrial pressure, improved left ventricular performance, preserved inotropic and lusitropic function with blunted remodeling. Secondary pulmonary hypertension was absent and right-sided cardiac pressures and function were preserved.

One-Year Outcomes After Transcatheter Insertion of an Interatrial Shunt Device for the Management of Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II-IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913613.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure: Rationale and Design of the Randomized Trial to REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I).

Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressure-either at rest or with exertion-is a common factor among all forms of HFpEF and one of the primary reasons for dyspnea and exercise intolerance in these patients. On the basis of clinical experience with congenital interatrial shunts in mitral stenosis, it has been hypothesized that the creation of a left-to-right interatrial shunt to decompress the left atrium (without compromising left ventricular filling or forward cardiac output) is a rational, nonpharmacological strategy for alleviating symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device has been developed and evaluated in patients with HFpEF in single-arm, nonblinded clinical trials. These studies have demonstrated the safety and potential efficacy of the device. However, a randomized, placebo-controlled evaluation of the device is required to further evaluate its safety and efficacy in patients with HFpEF. In this article, we give the rationale for a therapeutic transcatheter interatrial shunt device in HFpEF, and we describe the design of REDUCE Elevated Left Atrial Pressure in Heart Failure (REDUCE LAP-HF I), the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02600234.

Creating interatrial shunts in heart failure and pulmonary hypertension.

Patients with elevated filling pressures are at increased risk of adverse cardiovascular (CV) outcomes. Structural interventions to lower elevated either left or right atrial filling pressures are gaining attention. Studies in heart failure show that lowering left atrial pressure may reduce CV events while improving functional capacity. In recognition of this, trials are ongoing studying the effects of percutaneously implanted interatrial shunt devices (IASD). The preliminary results of IASD implantation suggest that periprocedural complications are rare and midterm safety good. Although both haemodynamic and functional parameters improve after IASD implantation, study designs, including sample size and duration, preclude definite conclusions regarding potential efficacy. In this paper, we briefly summarise current knowledge in the field, and give a perspective on the data needed to make interatrial device shunt therapy a part of our armamentarium in patients with heart failure or pulmonary hypertension and increased filling pressure.

A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial

Heart failure with preserved ejection fraction (HFPEF) is a common, globally recognised, form of heart failure for which no treatment has yet been shown to improve symptoms or prognosis. The pathophysiology of HFPEF is complex but characterised by increased left atrial pressure, especially during exertion, which might be a key therapeutic target. The rationale for the present study was that a mechanical approach to reducing left atrial pressure might be effective in HFPEF. The REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF) study was an open-label, single-arm, phase 1 study designed to assess the performance and safety of a transcatheter interatrial shunt device (IASD, Corvia Medical, Tewkesbury, MA, USA) in patients older than 40 years of age with symptoms of HFPEF despite pharmacological therapy, left ventricular ejection fraction higher than 40%, and a raised pulmonary capillary wedge pressure at rest (>15 mm Hg) or during exercise (>25 mm Hg). The study was done at 21 centres (all departments of cardiology in the UK, Netherlands, Belgium, France, Germany, Austria, Denmark, Australia, and New Zealand). The co-primary endpoints were the safety and performance of the IASD at 6 months, together with measures of clinical efficacy, including functional capacity and clinical status, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01913613. Between Feb 8, 2014, and June 10, 2015, 68 eligible patients were entered into the study. IASD placement was successful in 64 patients and seemed to be safe and well tolerated; no patient had a peri-procedural or major adverse cardiac or cerebrovascular event or need for cardiac surgical intervention for device-related complications during 6 months of follow-up. At 6 months, 31 (52%) of 60 patients had a reduction in pulmonary capillary wedge pressure at rest, 34 (58%) of 59 had a lower pulmonary capillary wedge pressure during exertion, and 23 (39%) of 59 fulfilled both these criteria. Mean exercise pulmonary capillary wedge pressure was lower at 6 months than at baseline, both at 20 watts workload (mean 32 mm Hg [SD 8] at baseline vs 29 mm Hg [9] at 6 months, p=0·0124) and at peak exercise (34 mm Hg [8] vs 32 [8], p=0·0255), despite increased mean exercise duration (baseline vs 6 months: 7·3 min [SD 3·1] vs 8·2 min [3·4], p=0·03). Sustained device patency at 6 months was confirmed by left-to-right shunting (pulmonary/systemic flow ratio: 1·06 [SD 0·32] at baseline vs 1·27 [0·20] at 6 months, p=0·0004). Implantation of an interatrial shunt device is feasible, seems to be safe, reduces left atrial pressure during exercise, and could be a new strategy for the management of HFPEF. The effectiveness of IASD compared with existing treatment for patients with HFPEF requires validation in a randomised controlled trial. Corvia Medical Inc.

Left-to-right atrial shunting: new hope for heart failure?

So far, no treatments have proven effective for heart failure with preserved ejection fraction—a syndrome with dismal prognosis. 1 Rossignol P Zannad F Regional differences in heart failure with preserved ejection fraction trials: when nephrology meets cardiology but east does not meet west. Circulation. 2015; 131: 7-10 Crossref PubMed Scopus (22) Google Scholar The syndrome is heterogeneous and associated with many comorbidities. Pathophysiology of the disorder is poorly understood, although a common hallmark is large artery stiffness and heart stiffness, whether related to fibrosis or myocardial titin-based stiffness. As a consequence, the heart's ability to cope with exercise-induced haemodynamic overload is restricted. Exercise would inevitably produce an abrupt rise in pulmonary and left atrial pressure, the main driver of dyspnoea in patients with heart failure with preserved ejection fraction. Dyspnoea is a highly distressing symptom and is the main reason for the frequent hospital admissions in these patients. In people with suspected heart failure with preserved ejection fraction, retrospective data suggest that invasive exercise testing substantially improves prediction of long-term mortality, since an excessive rise in pulmonary capillary wedge pressure during exercise despite a normal pressure at rest was associated with increased mortality. 2 Dorfs S Zeh W Hochholzer W et al. Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction. Eur Heart J. 2014; 35: 3103-3112 Crossref PubMed Scopus (172) Google Scholar Thus, high pulmonary capillary wedge pressure at rest or during exercise might be a therapeutic target in patients with heart failure with preserved ejection fraction. 3 Borlaug BA Koepp KE Melenovsky V Sodium nitrite improves exercise hemodynamics and ventricular performance in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2015; 66: 1672-1682 Crossref PubMed Scopus (154) Google Scholar Could left-to-right atrial shunting divert excessive pressure during exercise and serve as a decompression security valve? Cardiology technology—from old to newToday's Lancet brings together a collection of cardiology research and commentary ahead of the American College of Cardiology (ACC) Annual Meeting, Chicago, IL, USA (April 2–4). The theme of this year's meeting is ignite innovation, as the ACC invites delegates to think in new and disruptive ways, in the context of current rapid technological change. Full-Text PDF Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proof-of-principle cohort studyThis 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. Full-Text PDF A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trialImplantation of an interatrial shunt device is feasible, seems to be safe, reduces left atrial pressure during exercise, and could be a new strategy for the management of HFPEF. The effectiveness of IASD compared with existing treatment for patients with HFPEF requires validation in a randomised controlled trial. Full-Text PDF

Novel device-based interventional strategies for advanced heart failure.

While heart failure is one of the leading causes of mortality and morbidity, our tools to provide ultimate treatment solutions are still limited. Recent developments in new devices are designed to fill this therapeutic gap. The scope of this review is to focus on two particular targets, namely (1) left ventricular geometric restoration and (2) atrial depressurization. (1) Reduction of the wall stress by shrinking the ventricular cavity has been traditionally attempted surgically. Recently, the Parachute device (CardioKinetix Inc., Menlo Park, CA, USA) has been introduced to restore ventricular geometry and cardiac mechanics. The intervention aims to partition distal dysfunctional segments that are non-contributory to the ventricular mechanics and forward cardiac output. (2) Diastolic heart failure is characterized by abnormal relaxation and chamber stiffness. The main therapeutic goal achieved should be the reduction of afterload and diastolic pressure load. Recently, new catheter-based approaches were proposed to reduce left atrial pressure and ventricular decompression: the InterAtrial Shunt Device (IASD™) (Corvia Medical Inc., Tewksbury, MA, USA) and the V-Wave Shunt (V-Wave Ltd, Or Akiva, Israel). Both are designed to create a controlled atrial septal defect in symptomatic patients with heart failure. While the assist devices are aimed at end-stage heart failure, emerging device-based percutaneous or minimal invasive techniques comprise a wide spectrum of innovative concepts that target ventricular remodeling, cardiac contractility or neuro-humoral modulation. The clinical adoption is in the early stages of the initial feasibility and safety studies, and clinical evidence needs to be gathered in appropriately designed clinical trials.

Abstract 15897: Identification of Candidates for Novel Interatrial Shunt Devices Through Non-invasive Testing in Patients With Heart Failure and Preserved Ejection Fraction

Introduction: Interatrial shunt devices (IASD) are a novel therapeutic option for heart failure and preserved ejection fraction (HFpEF). IASDs work by decompressing the overloaded left atrium (LA) via shunting of blood to the right atrium (RA). Thus, optimal candidates for the IASD intervention will have an elevated pressure gradient between the LA and RA. We hypothesized that increased LA-RA gradient could be diagnosed non-invasively by echo. Methods: A total of 293 consecutive patients with HFpEF who also underwent invasive hemodynamic testing were were identified. All patients underwent comprehensive echo, including tissue Doppler. Patients were categorized into 2 groups based on the LA-RA pressure gradient (PCWP-RA pressure) at time of invasive hemodynamic testing (PCWP-RAP &gt; 10 mmHg [large pressure gradient] vs. PCWP 0-5 mmHg [low pressure gradient]), and clinical, laboratory, and echocardiography parameters were compared between groups. Results: Mean age was 64±12 years, 59% were female, 36% were African American, and comorbidities were common. Of the 293 patients, n=58 had PCWP-RAP gradient of 0-5 mmHg and n=114 had PCWP-RAP &gt; 10 mmHg, with the rest of the patients (n=56) in the PCWP-RAP 5-10 mmHg range. Patients with an elevated PCWP-RAP gradient were more often female and obese and less likely to have a history of atrial fibrillation (Table). On echocardiography, the 2 parameters that were most different between groups were TAPSE and lateral e’ velocity such that an elevated ratio of TAPSE to lateral e’ velocity identified patients with HFpEF who were most likely to have an elevated PCWP-RAP gradient &gt; 10 mmHg (area under the ROC curve = 0.69 [95% CI 0.60-0.78]; P=0.001). Conclusions: An elevated TAPSE/lateral e’ velocity ratio on echo in HFpEF is associated with invasive PCWP-RAP gradient &gt; 10 mmHg at rest and may aid in the identifying suitable HFpEF candidates who would benefit from an IASD.

Rationale and Design of the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (Reduce LAP-HF) Trial

ObjectiveHeart failure with preserved ejection fraction (HFpEF) is characterized by elevated left atrial pressure during rest and/or exercise. The Reduce LAP-HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial will evaluate the safety and performance of the Interatrial Shunt Device (IASD) System II, designed to directly reduce elevated left atrial pressure, in patients with HFpEF. MethodsThe Reduce LAP-HF Trial is a prospective, nonrandomized, open-label trial to evaluate a novel device that creates a small permanent shunt at the level of the atria. A minimum of 60 patients with ejection fraction ≥40% and New York Heart Association functional class III or IV heart failure with a pulmonary capillary wedge pressure (PCWP) ≥15 mm Hg at rest or ≥25 mm Hg during supine bike exercise will be implanted with an IASD System II, and followed for 6 months to assess the primary and secondary end points. Safety and standard clinical follow-up will continue through 3 years after implantation. Primary outcome measures for safety are periprocedural and 6-month major adverse cardiac and cerebrovascular events (MACCE) and systemic embolic events (excluding pulmonary thromboembolism). MACCE include death, stroke, myocardial infarction, or requirement of implant removal. Primary outcome measures for device performance include success of device implantation, reduction of PCWP at rest and during exercise, and demonstration of left-to-right flow through the device. Key secondary end points include exercise tolerance, quality of life, and the incidence of heart failure hospitalization. ConclusionReduce LAP-HF is the first trial intended to lower left atrial pressure in HFpEF by means of creating a permanent shunt through the atrial septum with the use of a device. Although the trial is primarily designed to study safety and device performance, we also test the pathophysiologic hypothesis that reduction of left atrial pressure will improve symptoms and quality of life in patients with HFpEF.

Management of a patient with preserved ejection fraction heart failure with an interatrial shunt device

Management of a patient with preserved ejection fraction heart failure with an interatrial shunt device

(198) - Percutaneous Implantation of a Novel Interatrial Shunt Device in Patients with Heart Failure and Preserved or Mildly Reduced Ejection Fraction: Initial Results of a Pilot Trial

Heart failure with preserved or mildly reduced ejection fraction (HFpEF) is common and, to date, therapeutic options are very limited. Increased left atrial pressure is the common hemodynamic abnormality in HFpEF. We report the one month outcome of patients treated with a novel device intended to lower left atrial pressure by creating a small permanent shunt in the atrial septum.

Effects of an Interatrial Shunt on Rest and Exercise Hemodynamics: Results of a Computer Simulation in Heart Failure

BackgroundA treatment based on an interatrial shunt device has been proposed for counteracting elevated pulmonary capillary wedge pressure (PCWP) in patients with heart failure and mildly reduced or preserved ejection fraction (HFpEF). We tested the theoretical hemodynamic effects of this approach with the use of a previously validated cardiovascular simulation. Methods and ResultsRest and exercise hemodynamics data from 2 previous independent studies of patients with HFpEF were simulated. The theoretical effects of a shunt between the right and left atria (diameter up to 12 mm) were determined. The interatrial shunt lowered PCWP by ∼3 mm Hg under simulated resting conditions (from 10 to 7 mm Hg) and by ∼11 mm Hg under simulated peak exercise conditions (from 28 to 17 mm Hg). Left ventricular cardiac output decreased ∼0.5 L/min at rest and ∼1.3 L/min at peak exercise, with corresponding increases in right ventricular cardiac output. However, because of the reductions in PCWP, right atrial and pulmonary artery pressures did not increase. A majority of these effects were achieved with a shunt diameter of 8–9 mm. The direction of flow though the shunt was left to right in all of the conditions tested. ConclusionsThe interatrial shunt reduced left-sided cardiac output with a marked reduction in PCWP. This approach may reduce the propensity for heart failure exacerbations and allow patients to exercise longer, thus attaining higher heart rates and cardiac outputs with the shunt compared with no shunt. These results support clinical investigation of this approach and point out key factors necessary to evaluate its safety and hemodynamic effectiveness.

Interatrial shunt closure devices in patients with nickel allergy

We assessed outcomes in nickel allergic patients treated with percutaneous interatrial shunt device closure with the Helex device. Nickel toxicity has been well described in patients undergoing interatrial shunt closure with the Amplatzer device, which has a nitinol design. There have been no reports using Helex in nickel allergic patients. Ninety-five consecutive patients underwent percutaneous interatrial shunt closure at a single US center by one operator. In those with possible nickel allergy, patch testing with the North American Contact Dermatitis Group standard series and a metal series was performed. The mean age was 48 +/- 16 years (range 18-81), 48% were male, 21 (22%) had atrial septal defect, and 74 (78%) had patent foramen ovale. Six patients had a positive skin test to nickel and underwent successful closure with Helex. Of the remaining 89 patients, 88 were closed with Amplatzer and one with Helex. All procedures were successful with no deaths, myocardial infarctions, strokes, or systemic emboli at six-month followup. None of the Helex patients developed an allergic reaction, significant chest pain, or arrhythmia. Of those without pre-procedural known nickel allergy, 12% had palpitations, 5% had atrial fibrillation, and 13% had chest pain. When compared with a published report that 89% of nickel-allergic patients developing an allergic reaction to the Amplatzer or Premere device, Helex appeared far safer in nickel allergic patients (P < 0.001). In patients with nickel allergy, percutaneous interatrial shunt device closure with Helex device is safe, and is not associated with allergy to nickel.