A Look at the NASPE Expert Consensus Statement on Resynchronization Therapy for Heart Failure

NASPE-Heart Rhythm Society issued an Expert Consensus Statement in December of 2003 entitled Resynchronization Therapy for Heart Failure.¹ This work was the culmination of dialogue which took place at NASPE 2003. This document represents the combined wisdom of the world s recognized experts in the field of heart failure management and device therapy. In this article, the author summarizes the salient points of this work. The authors began by defining heart failure (HF), and presented the standard epidemiologic data related to incidence and cost of the disease to society. The classification systems currently being used to stratify patients with heart failure were reviewed. The first was the well known New York Heart Association (NYHA) Classification System, which deals primarily with the degree of physical disability present. The newer system was the AHA/ACC Guideline, which utilizes parameters of disease evolution and progression (Table 1).² The purpose of the Resynchronization Therapy for Heart Failure document, as stated by the authors, was that it was an attempt to answer the following question: Do symptomatic HF patients with low ejection fractions and QRS prolongation derive an incremental benefit from the addition of cardiac resynchronization (CRT) or CRT-D (CRT with ICD) to optimal pharmacotherapy?

Electrical Remodeling

The well known process of mechanical remodeling in HF was reviewed, but there is also a process of electrical remodeling which takes place. There are multiple consequences of this electrical remodeling with advancing HF. These consequences include a prolongation in the duration of the action potential and alterations in the movement of calcium during the depolarization-repolarization process. As a result, a form of triggered automaticity/reentry combination occurs and may lead to a polymorphic ventricular tachycardia (VT) seen in congenital long QT syndromes. In addition, a reentrant monomorphic VT and conduction delay may ensue. As a result, a high incidence of sudden death is seen in the HF population along with a greater potential for experiencing the proarrhythmic effects of antiarrhythmic drugs. The incidence of QRS duration being greater than 120 ms in HF patients is 15% for all heart failure patients, and greater than 30% for those with moderate to severe symptoms. This conduction abnormality may lead to a mechanical dyssynchrony of contraction (leading to increase in mitral regurgitation, left ventricular (LV) systolic and diastolic delays and reduced diastolic filling times). A registry study from Italy collected data on 5,517 HF patients and found that left bundle branch block was associated with increased one-year mortality and risk from sudden cardiac death.³ It was theorized that cardiac resynchronization therapy should reverse/correct these effects. Various clinical trials have been conducted which have looked at the effects of CRT therapy alone and with ICD included. These trials have included PATH-CHF, PATH-CHF II, MUSTIC SR, MUSTIC AF, MIRACLE, CARE-HF, PAVE, MIRACLE ICD, VENTAK CHF/CONTAK CD, COMPANION, and PACMAN.⁴

Study Endpoints

A variety of study designs and inclusion/exclusion criteria were represented by these studies. However, there were commonalities within many studies related to study endpoints. Endpoints within multiple studies included: coronary sinus (CS) lead implant/system safety, functional class and quality of life, exercise capacity/VO2, measures of disease progression, and hospitalization/mortality (Table 2). Three studies examined issues of lead system implanting success and safety. Successful first-time placement occurred in 90% of cases. Lead placement skill increased with subsequent placements, demonstrating that there was a learning curve involved in coronary sinus lead placement. Risks with lead placement seemed to be comparable to that of standard systems. CS dissection incidence was 2-4%, and perforation of the coronary sinus was rare. There were no device-related deaths in these three studies. Five studies have reported results of functional class and quality of life measures after initiation of CRT therapy. CRT was seen to improve these parameters in each study, but the effect was rather limited to patients with NYHA classes III and IV. At least four studies have examined exercise capacity/VO₂ as an endpoint. A significant improvement in exercise capacity was seen with CRT. The cumulative results of four studies have reported on measures of disease progression as study endpoints. The effect of CRT over at least six months appeared to decrease ventricular size and improve systolic function. Diastolic function and sphericity do not appear to be affected. Left ventricular mass was decreased in one study.⁵ Another study reported that the withdrawal of CRT after one month led to reversal of the positive effects on the cardiac structures.⁶ Long-term follow-up and examination of structural effects were recommended as areas for future study. Five studies have examined/reported on the endpoints of hospitalization/mortality. They have reported that symptoms were improved post implant. All-cause mortality and all-cause hospitalization have also been reduced. The benefit from improved mortality rate, however, seems to be associated with the implant of CRT-D devices.

Expanding Indications for Electrical Heart Failure Devices

Three future areas of study for heart failure devices were discussed. The first was in the setting of chronotropic incompetence, a condition which occurs often in the HF setting as multiple drugs are being prescribed. The application of atrial rate support with group may prove to be beneficial. The incidence of atrial fibrillation increases as the severity of heart failure increases. It has been estimated that up to 50% of NYHA Class IV patients have atrial fibrillation, and it is thought to be a risk factor for increased mortality in the heart failure population. The use of atrial fibrillation management in combination with CRT has not been tested, but future trials will do so. Right heart hemodynamics can be measured through the use of a device currently being investigated. This technology offers the capability of monitoring right heart function, enabling appropriate pharmacologic intervention. The outcomes of these therapies can then be documented and guide subsequent interventions. Results from Heart Rate Variability Logs, which are included in the software of the CRT devices, have not been reported extensively in the literature. The predictive value of this information in suggesting increased probability of sudden cardiac death may prove this to be a valuable tool.

Technical Issues

The placement of leads in the CS increases the risk of procedural complications. In order to increase the safety of the procedure, it has been recommended that the implanter be familiar with over the wire techniques. The CRT device implant procedure should not last longer than four hours, as longer procedures tend to increase the potential for complications. In addition, if an ICD will also be implanted, it may be advisable to defer defibrillator testing to a later time if patient stability is in question. The implanter is advised to document the RAO and LAO venograms obtained prior to CS lead placement to assist in guiding current and future attempts at lead placements. Should the implanter fail to secure adequate lead placement through the transvenous approach, an epicardial approach may need to be considered. Another implantation-related issue involves the effect of atrial and ventricular remodeling, and how this may affect the anatomy of the CS. Increased right atrial pressure leads to atrial dilation, thus altering the shape of the right atrium. This shape may be altered from one that is tubular to one that is spherical. The angulation of the CS may also be altered due to the remodeling of the left ventricle, which causes dilation of the mitral annulus and thus impacts on CS and great cardiac vein position. This leads to increased difficulty in lead placement. In addition, the veins that follow diseased arteries may be excessively tortuous and further challenge the implanter. Coronary sinus epicardial capture thresholds differ from those seen with right ventricular (RV) endocardial pacing. Stimulation of the LV occurs through the venous wall as opposed to RV stimulation which is against the endocardium. In addition, the LV electrode-myocardial interface distance is greater. With the current systems, separate output circuits exist for the right and left, and current is controlled separately. Thus, the timing of left and right stimulation can vary.

Resynchronization and Outcomes

The criteria for optimization of the AV interval in the acute phase (post implant) has not been well tested/defined. The goal for AV optimization has been to determine the AV interval that maximizes left ventricular filling and stroke volume. The timing of events in CRT may not be consistent, based on whether the atrium is sensed or paced, and also based on the placement of the right atrial lead. Formulas for AV interval programming and methods for assessing the hemodynamics of such programming have varied. Also, it is not known which AV optimization parameters are ideal for follow-up of the chronic CRT patient. The method of selection of LV stimulation site has not been standardized. Multiple measures of LV hemodynamics have been used for assessment of lead placement. Many parameters have been used to measure the clinical outcomes of CRT. These have included peak oxygen consumption on cardiopulmonary exercise testing, the six-minute walk distance, and echocardiographic measures of LV size and function. Brain natiuretic peptide (BNP) is being used in some studies not yet reported. CRT alone has impacted all of the aforementioned parameters but not mortality. However, CRT-D has impacted on all of these plus mortality rate. Echocardiography is the most commonly used tool examine the impact of CRT on the heart muscle. Serum markers are being utilized in some of the newer studies, i.e. norepinephrine, brain natiuretic peptide, and tumor necrosis factor. Data is also being collected on arrhythmia frequency post CRT.

Certification

The consensus group issued suggested guidelines for training of implanters of CRT devices. The official NASPE guidelines for pacemaker and defibrillator implantation are in the revision process at the present, and will be reissued with new CRT implantation guidelines included. Codes for Resynchronization Therapy In January of 2003, new physician billing codes (CPT) were made available for use of the coronary sinus lead (Table 3). This follows new hospital DRG codes for resynchronization therapy, which had been issued in 2002 (Table 4).

Summary Guidelines

The summary guidelines for the conference were presented in a flow diagram which attempted to provide a road map for treatment of the HF patient: Patients with EF Conclusion The authors concluded that there are certain issues that must be dealt with in the care and management of the CRT patient. These include long-term benefit concerns, the complexity of the devices that are being developed, optimization of implantation and programmability, and identifying those patients who will benefit most from therapy. In addition, the economics of treatment and ethics must be addressed. Much work has been done, but many challenges await!

Disclosure: The author reports financial interest in the form of stock ownership in Guidant and Medtronic, and also that these companies provide financial support to the author s Order and Disorder Electrophysiology Training Program.