Case Study

Non-responder to Responder: Optimization of Cardiac Resynchronization Therapy Using Gas Exchange

Krishan K. Kataria, MD1, Sana Grover, MBBS2, Abraham G. Kocheril, MD, FACC, FACP, FHRS3
1Christie Clinic, Urbana, Illinois, 2Pt. B.D.S. PGIMS Rohtak, India, 3Presence Medical Group, University of Illinois at Urbana-Champaign

Krishan K. Kataria, MD1, Sana Grover, MBBS2, Abraham G. Kocheril, MD, FACC, FACP, FHRS3
1Christie Clinic, Urbana, Illinois, 2Pt. B.D.S. PGIMS Rohtak, India, 3Presence Medical Group, University of Illinois at Urbana-Champaign


Cardiac resynchronization therapy (CRT) is an established device treatment for patients with advanced heart failure.1 However, in randomized clinical trials, about 30% of the patients were identified as non-responders.2-3 Device optimization is an important post-implantation option that can positively impact the outcome in this patient population. In this case report, we describe the role of cardiopulmonary exercise testing in device optimization in a patient with CRT implantation for ambulatory New York Heart Association (NYHA) class IV congestive heart failure (CHF). 

Case description

A 77-year-old man with ischemic cardiomyopathy presented to our clinic for a second opinion regarding left ventricle (LV) lead placement for completion of a CRT device. In a previous procedure at another facility, LV lead placement was unsuccessful, and an epicardial LV lead was recommended. Despite being on maximal medical management, the patient continued to be in NYHA functional class IV CHF. He underwent successful implantation of a percutaneous LV lead to complete the CRT device at our center. Immediately after CRT was activated, he had improvement in his symptoms to NYHA class III, but his overall exertion tolerance remained limited. Device programming led to the desired EKG changes (including QRS narrowing), but on three-month follow-up, the patient continued to be in NYHA functional class III. 

To achieve dynamic device optimization, a cardiopulmonary exercise test was scheduled. Using the Shape-HF™ Cardiopulmonary Exercise Testing System (Shape Medical Systems, Inc.), key measurements obtained included the ventilatory efficiency slope (VE/VCO2), change in cardiac output in relation to pulmonary flow with exercise (delta PetCO2), and heart rate response to exercise.4 The ventilation/perfusion ratio suggested that heart failure was the primary cause of his poor functional status and dyspnea. Multiple VV delay settings were tested, and on the basis of the relative cardiopulmonary response, the device was programmed to a VV delay of 20 ms with LV first. 

The patient showed significant clinical improvement on subsequent follow-up, with his NYHA functional class improving to II. These benefits persisted at one-year follow-up.


Cardiac resynchronization therapy by biventricular pacing has shown significant mortality and morbidity benefit in patients with advanced heart failure. Despite the advances in therapy, a substantial number of patients did not respond to the device therapy in randomized, controlled trials. Device optimization is an important tool that can help in improving clinical outcomes in the post-implantation patient population. 

Device optimization utilizes the programming of atrioventricular (AV) and interventricular (VV) intervals to achieve the desired hemodynamic and clinical outcomes. Most of these attempts are based on either resting echocardiography-guided techniques or heart sound/EKG-based techniques.5 These methods are based upon the resting state (static optimization), and do not take into account the dynamic physiologic changes in the heart and lungs during activity. Cardiopulmonary testing is a non-invasive method to obtain key measurements during exercise, including the ventilatory equivalents for a given metabolic demand, end-tidal CO2, and breathing effort. Cardiopulmonary exercise testing has emerged as a valuable diagnostic tool for objectively quantifying functional status in patients with heart failure. 

Cardiopulmonary exercise testing provides an opportunity to optimize AV and/or VV intervals in a CRT device during physical exertion, which can mimic the device performance in real-world situations when patients perform activities of daily living rather than at rest. A study by MacCarter et al demonstrated that CRT device optimization based on cardiopulmonary exercise testing is feasible, and that in their patient population, led to significantly improved ventilation efficiency indices both acutely and chronically.6 

We used this approach of device optimization in our patient using the Shape-HF cardiopulmonary exercise equipment. Using this technique to optimize to the best ventilatory parameters (breathing) rather than stroke volume, a change in VV delay was achieved that produced the most optimal clinical benefit as demonstrated by the favorable change in the patient’s NYHA class.


CRT is a potent treatment modality that improves quality of life, functional class, and prolongs life in patients with advanced systolic heart failure. CRT device optimization based on cardiopulmonary exercise testing can lead to significant clinical improvement and should be considered in patients who fail to show initial clinical improvement after device implantation.

Disclosures: The authors have no conflicts of interest to report regarding the content herein.


  1. Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012;60(14):1297-1313.
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  3. Young JB, Abraham WT, Smith AL, et al, Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD trial. JAMA. 2003;289:2685-2694.
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  5. Ellenbogen KA, Gold MR, Meyer TE, et al. Primary results from the SmartDelay determined AV optimization: a comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial: a randomized trial comparing empirical, echocardiography-guided, and algorithmic atrioventricular delay programming in cardiac resynchronization therapy. Circulation. 2010;122:2660-2668.
  6. MacCarter D, Miler FC, Gilmet KB, et al. Acute and chronic improvement in breathing efficiency with exercise based AV/V-V CRT optimization. J Card Fail. 2008;14(6):S63.