Some Things We Just Can’t Have: The Demise of LAPTOP

There are many patients with heart failure (HF), with or without ventricular dysfunction, who have recurring hospitalizations for breathlessness and can be difficult to manage. Often one’s ability to determine a patient’s volume status by exam is limited, particularly in patients with obesity and underlying lung disease. An ideal of many HF specialists is to be able to look at a patient with HF and know exactly what his or her left atrial pressure is. For the past several years, various implantable hemodynamic sensors have been developed to measure intracardiac pressure to guide the management of patients with HF. Such devices include right ventricular, pulmonary artery, and left atrial pressure sensors.¹  

The LAPTOP-HF study is (was) a prospective, multi-center, IDE trial that involved placement of a left atrial pressure (LAP) transducer, sponsored by St. Jude Medical. Patients with class III HF for at least 6 months and at least one hospitalization in the past year were enrolled and stratified based on whether or not the ejection fraction was ≤ or >35%, and whether or not they had an indication for cardiac resynchronization therapy. Patients were randomized 1:1 to either treatment group, and had the LAP sensor implanted, ongoing LAP readings utilizing a personal monitor device, and LAP-based medication dosing, or a control group with no LAP sensor implant, but which received the personal monitor device for medication reminders. The goal was to enroll 730 patients at up to 75 U.S. sites.

The LAP is attached to the end of a transvenous pacing-type lead. The distal end of the lead houses the sensor and is placed in the LA using a transfemoral, transseptal approach. The proximal end of the lead is then snared from the femoral site using a subclavian/superior vena cava approach and pulled to the shoulder. The lead is attached to a generator-type device that is placed in the infraclavicular subcutaneous region like a pacemaker. An external communication device can retrieve the atrial intracardiac electrograms and LA pressure. Although the procedure is technically challenging, and enrollment in the trial was slow, over half of the enrollment target was met and much was learned. 

In one patient who was enrolled in the LAPTOP study at Northwestern, a LAP sensor and a dual chamber implantable cardioverter defibrillator (ICD) were implanted during the same procedure using two separate devices placed close to each other in a left subcutaneous pocket. However, the patient developed progressive HF and QRS widening after several months. Therefore, he underwent upgrade of the ICD to a cardiac resynchronization therapy defibrillator (CRT-D). Figure 1 shows the elegant ability of the LAP sensor to detect and display a reduction in left atrial pressure during delivery of CRT. 

In early June 2014, the Data and Safety Monitoring Board terminated the LAPTOP-HF trial before completion. The decision was apparently based on futility to reach the primary endpoint, and a concern over a high number of implant-related complications related to transseptal catheterization. Much was learned during the LAPTOP-HF trial related to the ability to directly measure LAP in patients with HF. It will be interesting to see how well the recently FDA-approved pulmonary artery pressure sensor provides similar hemodynamic information. Just as importantly, however, there may also be a lot to learn from the early study termination of LAPTOP-HF. 

Despite the power and appeal of the data obtained from a permanently implanted lead in the LA that is able to continuously measure intracardiac pressure in patients with HF, there may be some data that we just can’t have. For some technologies, the risks related to getting the information are just not worth the benefit to the patient. Specifically, we learned from LAPTOP-HF that transseptal catheterization is a procedure that has inherent risks that cannot always be avoided, even in the hands of seasoned clinical investigators, is associated with severe complications such as aortic puncture and cardiac perforation, is more challenging when performed in patients with advanced HF and a severely dilated heart, and is a skill that requires a great deal of experience and expertise. It is a lesson that should be strongly considered when, and if, new therapies such as left atrial appendage occlusion, which requires transseptal catheterization, becomes commercially available and decisions are made regarding the training and background that will be required by physicians who will be doing these procedures.

Reference 

1. Ritzema J, Troughton R, Melton I, et al. Physician-directed patient self-management of left atrial pressure in advanced chronic heart failure. HOMEOSTASIS Study Group. Circulation. 2010;121:1086-1095.