Electrical Bioimpedance for Cardiac Output Monitoring

CMS NCA document | source_status=Closed | review_type=2nd Recon | public_comment_open=False | document_id=CAG-00001R2

CMS was asked to make a National Coverage Determination (NCD) that would expand Medicare coverage to include Transthoracic Electrical Bioimpedance (TEB) for the management of drug resistant hypertension and additional types of hypertension. Our existing policy permits Medicare contractors to determine whether or not TEB is reasonable and necessary under § 1862(a)(1)(A) for management of drug resistant hypertension. 20.16(A)(2) of the Medicare National Coverage Determination Manual. After considering the additional evidence, we have determined that the evidence does not warrant expanded coverage at this time. Still, we will retain our policy permitting Medicare contractors to make a reasonable and necessary determination under § 1862(a)(1)(A) for the use of TEB in the management of drug resistant hypertension in beneficiaries.

Decision Memo: To: Administrative File: CAG #00001R2 Electrical Bioimpedance for Cardiac Output Monitoring From: Steve Phurrough, MD, MPA Director, Coverage and Analysis Group; Louis Jacques, MD Division Director Francina C. Spencer Lead Analyst Madeline Ulrich, MD, MS Lead Medical Officer Subject: Coverage Decision Memorandum for Electrical Bioimpedance for Cardiac Output Monitoring Date: November 20, 2006 I. Decision CMS was asked to make a National Coverage Determination (NCD) that would expand Medicare coverage to include Transthoracic Electrical Bioimpedance (TEB) for the management of drug resistant hypertension and additional types of hypertension. Our existing policy permits Medicare contractors to determine whether or not TEB is reasonable and necessary under § 1862(a)(1)(A) for management of drug resistant hypertension. 20.16(A)(2) of the Medicare National Coverage Determination Manual. After considering the additional evidence, we have determined that the evidence does not warrant expanded coverage at this time. Still, we will retain our policy permitting Medicare contractors to make a reasonable and necessary determination under § 1862(a)(1)(A) for the use of TEB in the management of drug resistant hypertension in beneficiaries. II. Background The American Heart Association, in a scientific statement published in its journal Hypertension, on January 24, 2006, reported that 27 % of adult Americans have hypertension. Statistics published on the Association’s web site indicate that nearly 2/3 of people do not know they have the condition, and that 70% of patients under treatment do not have the condition controlled. The cause is unknown in 90-95% cases of hypertension, although a number of known risk factors may contribute to its development. Cases without specifically recognized causes are referred to as essential hypertension. In the relatively small number of cases in which another discrete disease process, such as renal artery stenosis, is found to cause the elevation of blood pressure, it is then referred to as secondary hypertension. The rationale for treating hypertension, which in and of itself is asymptomatic, is the prevention of end organ damage, e.g. stroke, kidney failure, heart failure, that may develop in patients who have had high blood pressure for many years. Blood pressure (BP) is reported in millimeters of mercury (mmHg) with two numbers. The first number is the systolic pressure and is a measure of the force of blood propelled through arteries with each contraction of the left ventricle of the heart. The second number is the diastolic pressure and is a measure of the force exerted by blood flow in the arteries between left ventricular contractions. High blood pressure or hypertension is diagnosed by multiple measurements with a medical instrument known as a sphygmomanometer, commonly referred to as a blood pressure cuff. In a given individual, measured blood pressure will vary in response to many factors, including recent physical exertion, fluid status, site of measurement (e.g. left arm, right arm, thigh), the size of the blood pressure cuff, and other factors. Thus, the value of an isolated blood pressure measurement is minimal, and common practice is to base treatment decisions on multiple measurements over time. The measurement should be performed by a qualified health care professional with the patient at rest. Measurements greater than or equal to 140(systolic)/90(diastolic) recorded on multiple occasions are sufficient for the diagnosis of hypertension or high blood pressure. Lower cutoff values have been advocated for some patient populations predisposed to end organ damage, e.g. diabetics. Treatment of newly diagnosed essential hypertension usually begins with recommendations for lifestyle modification to temper the effects of known risk factors and prevent or delay progression to end organ damage, particularly to the cardiovascular system. Recommended lifestyle changes may include regular exercise, smoking cessation, decreased alcohol intake, sufficient rest, and changes to reduce dietary sodium and fat content as well as to maintain or attain a healthy weight. If goal blood pressure has not been achieved after a reasonable trial of lifestyle modification, or in the presence of comorbid conditions or predisposing inherited factors, antihypertensive medication is usually prescribed. Usual current recommendations are to begin treatment with a thiazide diuretic (unless contraindicated) and, if goal is still not reached, to add one or two additional medications at therapeutic dose levels until pressure is controlled. Medications have side effects that may be difficult for some patients to tolerate, or the particular drug combination chosen may not sufficiently reduce blood pressure in a particular patient. Physicians may try several drug combinations over a period of time, along with continuance of lifestyle modifications, before achieving long lasting control. Though there are many individual drugs that may be used for blood pressure control, the actual number of therapeutic options available to treat the patient is somewhat limited. Individual antihypertensive medications typically fall into one of several pharmacologic classes: diuretics, beta adrenergic blockers (β blockers), alpha blockers, calcium channel blockers (CCBs), vasodilators, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) and centrally acting agents. Within a given class, individual drugs generally lower blood pressure through a common mechanism and display similar side effects. Thus, if a patient fails to respond favorably to a particular drug it is less likely that he will respond favorably to another drug in the same class. With few exceptions, e.g. concurrent use of a potassium sparing and a non-potassium sparing diuretic, patients rarely are prescribed concurrent therapy with multiple drugs belonging to the same class. Generally, the treating practitioner will initiate a new medication at a lower than maximum dose and, if the target blood pressure is not achieved will titrate upwards until the patient experiences intolerable side effects, the maximum labeled dose is reached, or the blood pressure goal is attained. The proposed role of TEB measurement in the treatment of hypertension is that medication choices based on TEB results may lead to normalization of hemodynamic parameters. In theory, this will in turn result in better BP control. A recent review article listed a number of hemodynamic parameters that TEB is capable of measuring: (Ventura et al, 2005.) These are listed below. stroke volume (SV) “the amount of blood ejected from the left ventricle” systemic vascular resistance (SVR) “the force the left ventricle must overcome to expel blood into the systemic vasculature, also called total peripheral resistance” cardiac output (CO) “the flow of blood pumped by the heart each minute”, the product of the heart rate (HR) and SV mean arterial pressure (MAP) “the product of two hemodynamic components, CO and SVR” thoracic fluid content (TFC), “an index of fluid” with an inverse relationship to total thoracic impedance In our prior reconsideration decision, two other hemodynamic measures were defined. cardiac index (CI), “the CO divided by the patient’s body surface area” and systemic vascular resistance index (SVRI), which is computed from the CI and stroke volume III. History of Medicare Coverage There have been two previous decisions relating to coverage of Electrical Bioimpedance for Cardiac Output Monitoring. Under the first TEB coverage determination, effective July 1, 1999, TEB was covered for the “noninvasive diagnosis or monitoring of hemodynamics in patients with suspected or known cardiovascular disease.” The NCD did not specifically mention use of TEB in connection with treatment of hypertension, nor had evidence for such use been submitted. On August 7, 2003, CMS issued a reconsideration decision memorandum which clarified the circumstances under which TEB use would be considered reasonable and necessary. Upon review of evidence related to hypertension CMS determined that the coverage and description of the specifics of the situation in which TEB is reasonable and necessary for the treatment of drug resistant hypertension is left to contractor discretion, and that all other uses of TEB for hypertension are noncovered. Current Request On February 28, 2006, CMS opened a reconsideration of NCD 20.16 at the request of CardioDynamics. “The purpose of this letter is to formally request that CMS reconsider TEB coverage in hypertension and issue an NCD with the following language: “TEB is covered for the management of hypertensive patients on one or more antihypertensive drugs who are not at goal blood pressure. TEB is covered for hypertension that is essential or secondary, benign or malignant, or with or without comorbidities.” By letter on September 23, 2006, the requestor sought to revise its request to: “ TEB is covered for the following subgroup of patients with hypertension: 1. Hypertensive patients who are not at goal BP on three or more antihypertensive drugs. 2. High-risk hypertensive patients who are not at goal BP on two or more antihypertensive drugs. High-risk patients are defined by JNC guidelines and include patients with: a. Diabetes mellitus; b. Chronic kidney disease, defined as GFR <60 ml/min or albuminuria (>300 mg/d or 200 mg albumin per gram of creatinine). Conditions Prior to receiving a TEB test for hypertension, the patient must have been diagnosed and treated for hypertension a period of at least six months. Frequency Limitation TEB testing for hypertension as a covered indication is limited to a maximum of four tests per patient in a 12 month period. If a patient has received a previous TEB test for hypertension, an additional TEB test for hypertension cannot be performed for at least 30 days. Noncoverage TEB for hypertension is not covered: a) as a screening test; b) for any patient already at goal BP; c) for any patient not at goal BP on only one antihypertensive drug.” These requests are for expansion of coverage under the current benefit category, Benefit Category Medicare is a defined benefit program. An item or service must fall within a benefit category as a prerequisite to Medicare coverage. § 1812 (Scope of Part A); § 1832 (Scope of Part B) § 1861(s) (Definition of Medical and Other Health Services). At a minimum, TEB is considered to be within the benefit category of Diagnostic Tests (other). §1861(s)(3) This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service. IV. Timeline of Recent Activities Date Action February 28, 2006 CMS accepts a formal request for reconsideration of TEB for expanded coverage for hypertension. A tracking sheet was posted on the web site and the initial 30 day public comment period commenced. March 30, 2006 The initial 30 day public comment period ended. April 6, 2006 Public comments posted to the web site. August 24, 2006 The proposed decision memorandum inviting public comments was posted. The 30 day public comment period began. September 23, 2006 The second 30 day public comment period ended. September 23, 2006 Revised coverage request received. V. FDA Status Companies manufacturing TEB devices have obtained clearance for marketing of these devices under the Food and Drug Administration’s (FDA) 510(k) process. The FDA considers TEB devices to be Class II devices. The predicate devices upon which clearance was based are previous cardiac output monitors employing impedance plethysmography. Several TEB devices have been cleared through the FDA for marketing to monitor hemodynamic parameters. VI. General Methodological Principles When making national coverage determinations, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within a benefit category is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. The critical appraisal of the evidence enables us to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for patients. An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary. A detailed account of the methodological principles of study design that the agency utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix A. In general, features of clinical studies that improve quality and decrease bias include the selection of a clinically relevant cohort, the consistent use of a single good reference standard, and the blinding of readers of the index test, and reference test results. Public comment sometimes cites the published clinical evidence and gives CMS useful information. Public comments that give information on unpublished evidence such as the results of individual practitioners or patients are less rigorous and therefore less useful for making a coverage determination VII. Evidence A. Introduction We are providing a summary of the evidence that we considered during our review. We considered additional evidence submitted during the two public comment periods. A reasonable and necessary diagnostic test must provide information that is used by the treating physician to appropriately guide the management of the patient’s specific medical problem. 42 CFR. § 410.32(a) A principal outcome of interest in assessing the utility of a diagnostic test is its ability to improve health outcomes of persons who are tested. B. Discussion of evidence reviewed 1. Question: Is the evidence sufficient to conclude that hemodynamic monitoring with thoracic electric bioimpedance (TEB), when used by the treating physician to guide management of the patient’s medical problem, improves health outcomes in Medicare beneficiaries with hypertension who are on one or more antihypertensive drugs and who are not at goal blood pressure? 2. External technology assessments CMS did not commission a new external technology assessment (TA) for the current reconsideration request; however, the Agency for Healthcare Research and Quality (AHRQ) did complete a TA on TEB under contract from CMS in 2002. That assessment may be found on the CMS website at http://www.cms.hhs.gov/mcd/viewtechassess.asp?id=23 . CMS was unable to locate any other TAs for TEB. 3. Internal technology assessments CMS performed an extensive literature search utilizing PubMed for new randomized controlled trials (RCTs) and systematic reviews evaluating the use of TEB in the medical management of hypertensive patients. The literature search was limited to the English language and specific to the human population. The CONTROL study provides the only new peer-reviewed published RCT data on the use of TEB in the management of ambulatory hypertensive patients since our previous TEB reconsideration. The terms ICG (impedance cardiography) and TEB are used interchangeably in documents. The current request for coverage of TEB in the management of hypertension included ten documents, most prominent of which was the recently published “Consideration of Noninvasive Hemodynamic Monitoring to Target Reduction of Blood Pressure Levels” (CONTROL) study (Smith et al, 2006). This publication was accompanied by a published editorial comment and will be presented in greater detail below. The requestor also submitted a manuscript describing a cost effectiveness analysis of TEB. CMS does not consider cost in making NCDs. This policy is explicitly noted in a guidance document that is publicly available at the URL below. http://www.cms.hhs.gov/mcd/ncpc_view_document.asp?id=6 "Cost effectiveness is not a factor CMS considers in making NCDs. In other words, the cost of a particular technology is not relevant in the determination of whether the technology improves health outcomes or should be covered for the Medicare population through an NCD." Other documents submitted by the requestor are listed below. Full citations are provided in the References section. Sramek BB, Tichy JA, Hojerova M, Cervenka V, 1996: Normohemodynamic Goal-Oriented Antihypertensive Therapy Improves The Outcome (abstract only) This abstract was submitted in support of the last TEB reconsideration request, however no published, peer-reviewed, study is available and therefore it was not used in our analysis. Sharman DL, Gomes CP, Rutherford JP. 2004: Improvement in Blood Pressure Control With Impedance Cardiography-Guided Pharmacologic Decision Making This study reports on “impedance cardiography” or ICG (another term for TEB) use in the treatment of 21 older patients whose blood pressure was uncontrolled on two medications. There was no control group. All patients received the same number of visits and ICG measurements and were treated according to the algorithm reported in Hypertension which was extensively reviewed in the last CMS reconsideration decision. (Taler SJ, Textor SC, Augustine JE, 2002) Overall, participants’ entry systolic blood pressure (SBP) was 157.2 ± 13.9 and diastolic blood pressure (DBP) was 78.7 ± 9.9. At the end of three months SBP was 147 ± 18 and DBP was 76 ± 11. Subgroup analysis showed that twelve patients (57.1%) achieved blood pressure <140/90, (SBP 126.6 ± 7.8, DBP 73.9 ± 9.7) while nine (42.9%) had final blood pressure >140/90, (SBP 160.7 ± 81.3, DBP 81.3 ± 11.1). The authors state that the difference in results between subgroups is that patients achieving better control reduced their systemic vascular resistance index (SVRI, measured as dyne x sec x m² x cm 5 ) to a greater extent though use of ICG measurements. ( p<0.05 ) Entry SVRI Final SVRI Lower BP group 2986 ± 806 2640 ± 697 Higher BP group 2923 ± 645 3076 ± 468 The authors conclude that patients who were unresponsive to treatment “have an obvious need for further dose or drug changes” such as “intensification of a diuretic regimen” as was done in the 2002 Taler study. However, “(d)iuretics were not widely prescribed in this group…due to patient and physician preference with an appreciation of increased symptoms, and patient noncompliance…often associated with diuretics.” It is not clear how problems of physician and patient preference and non-compliance are improved through ICG or TEB, and authors conclude that “(a)dditional reports will continue to refine the role of ICG in the treatment of hypertension.” Sanford T, Treister N, Peters C, 2005: Use of Noninvasive Hemodynamics in Hypertension Management (report of three cases). The authors report improved blood pressure control in three patients, four to six weeks after medication changes suggested by ICG data. They conclude “individualized approach to therapy may lead to fewer side effects from medications and reduce the number of visits required to achieve BP control.” The small number of patients and short follow-up are insufficient to provide information useful to the current decision. Ashida T, Nishioeda Y, Kimura G, Kojima S, Kawamura M, Imanishi M et al. 1989: Effects of Salt, Prostaglandin, and Captopril on Vascular Responsiveness in Essential Hypertension. This article provides a brief discussion of mechanisms of hypertension and does not include discussion of the use of TEB. Alfie J, Waisman GD, Galarza CR, Magi MI, Vasvari F, Mayorga M et al., 1995: Relationship Between Systemic Hemodynamics and Ambulatory Blood Pressure Level are Sex Dependent This study compares sex-related differences in hypertensive men and women using impedance cardiography to estimate hemodynamic measures and ambulatory monitoring to record blood pressure. The authors concluded that the relationship of “hypertension severity and systemic vascular resistance was dependent on the sex of the patient.” This was not a treatment study and did not provide information as to how the results should be used in management of hypertension. Galarza CR, Alfie J, Waisman GD, Mayorga LM, Camera LA, del Rio M et al.1996: Diastolic Pressure Underestimates Age-Related Hemodynamic Impairment The authors compared demographic and hemodynamic data (obtained with ICG) to “demonstrate simultaneous age-related impairment in vascular resistance and arterial compliance,” which suggest that SBP, but not DBP, is a reliable indicator of hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly. The goal of the study was explanation of mechanisms, not treatment, and it did not show how this information should be used to establish improved blood pressure control. Hinderliter AL, Blumenthal JA, Waugh R, Chilukuri M, Sherwood A, 2004: Ethnic Differences in Left Ventricular Structure: Relations to Hemodynamics and Diurnal Blood Pressure Variation One hundred seventy-one men and women, aged 25 to 45 years, equally divided between those with “normal” BP (<140/85 mmHg) and those with “marginally elevated” BP (140-160/85-95 mmHg) received various measurements including ICG, office and ambulatory BP, echocardiograms, Doppler studies and various blood chemistries, which showed “greater left ventricular relative wall thickness in African American subjects as compared to whites with similar levels of resting BP.” The authors believe this difference “may be mediated, in part, by hemodynamic influences” and that “enhanced understanding of the genetic and environmental factors that determine these differences in left ventricular load may result in interventions that could lessen the burden of hypertensive heart disease in African Americans.” Goal of study was not blood pressure treatment, but rather to explain the reasons for differences in left ventricular structure observed in young African American hypertensives. The study did not show how this information could be used to improve blood pressure control. Hinderliter AL, Sherwood A, Blumenthal JA, Light KC, Girdler SS, McFetridge J et al., 2002: Changes in Hemodynamics and Left Ventricular Structure After Menopause Sixty-four premenopausal and 54 postmenopausal women, aged 47 to 55 years with screening BP <180/90 mmHg were studied. They underwent various measurements including ICG, office and ambulatory BP, echocardiograms, Doppler studies, and various blood chemistries. The authors note “that menopause is associated with concentric remodeling of the left ventricle… characteristically seen in subjects with increased peripheral resistance and…associated with and enhanced risk of cardiovascular events.” And, “(d)espite nearly identical blood pressures at rest, post menopausal women had a significantly higher peripheral vascular resistance than premenopausal subjects.” The study confirmed earlier investigations, which showed echocardiographic and hemodynamic changes associated with menopause. The study did not suggest how this information could be used to improve blood pressure control. CMS also noted reference to nine articles in the February 2005 Supplement to the American Journal of Hypertension. One of those articles (Sanford T, Treister N, Peters C, 2005) was submitted with the reconsideration request and is discussed above. We reviewed the other eight articles, but none involved a clinical study using TEB to manage hypertension. Overall, they suggested areas for additional study, but did not provide evidence on health outcomes related to the use of TEB in the Medicare population for the current reconsideration. A review article (Ventura HO, Taler SJ, Strobeck JE, 2005) concluded that “future studies will confirm recent findings that hemodynamic measurements in individual patients will improve diagnosis, risk assessment and treatment for these patients. It is also possible that further exploration of the implications of hypertension as a hemodynamic disease will lead to studies demonstrating that earlier detection and treatment of the hemodynamic components of hypertension may change the natural history of this disease process.” Another article (Abdelhammed AI, Smith RD, Levy P, Smits GJ, Ferrario CM, 2005), found differences in “hemodynamic profiles between hypertensive and nonhypertensive subjects”…which “may be helpful in diagnostic, prognostic and therapeutic decision making in hypertensive subjects.” The article concluded that “significant variation in hemodynamic values among BP categories exists. Hemodynamic findings in an individual patient cannot be predicted by BP values, demographic information, or medications. Noninvasive ICG can help to characterize hemodynamic values and to identify variance at similar BP levels, which may improve BP management.” These articles have been listed in the bibliography for reader reference. Summary of the CONTROL trial No new evidence was submitted with the revised coverage request dated September 23, 2006; however, the document contained responses to issues raised in our draft decision memorandum, which will be discussed below. The stated hypothesis of the CONTROL trial was that “ICG-guided treatment could aid physicians in reducing BP more effectively than standard care in a population of uncontrolled hypertensive patients receiving 1 to 3 medications in a primary care setting.” Between November 2002 and November 2004, eleven primary care centers screened 262 patients with a diagnosis of essential hypertension, aged 18 to 75, on 1 to 3 antihypertensive medications with systolic BP140-179 mmHg and/or diastolic BP 90-109 mmHg. Exclusion criteria were: >3 antihypertensive medications, history of heart failure, ejection fraction (EF) <40%, atrial fibrillation, severe valvular or renal disease, nephrotic syndrome, cirrhosis, and a cerebrovascular event within 3 months. Patients were also excluded if they had “abnormal laboratory findings” that are not further described, nor were any laboratory values reported in the study. By letter the requestor has advised that these lab values were: Hematology: hemoglobin <10g/dL; WBC <2000/mL; platelets <100,000/mL Blood chemistries: ALT and/or AST >2.5x upper limit of normal; creatinine >3.0mg/dL; potassium <3.3mEq/dL; Hemoglobin A1c > 10% Technical limitations of ICG also caused exclusion for height <47 or >75 inches, weight <66 or >341 pounds, hypersensitivity to sensor gel or adhesive, skin lesion at a sensor site, or the presence of activated minute-ventilation pacemaker. One-hundred eighty-four patients were randomized in a 3:2 ratio to either standard care or ICG-guided care. After randomization, 18 patients were excluded for BP < 140/90 upon remeasurement, and 2 patients withdrew early from the study. No information was provided about the method of randomization in the published report of the trial. The requestor subsequently advised CMS that all trial participants remained under the treatment of their usual physicians. By letter we were advised that “Randomization was stratified by site with block randomization through a central telephone service”. The duration of the selection process and how the actual selections were made has not been provided and we have not determined what other efforts may have been employed to reduce bias. The authors did not indicate the number of patients lost in each study arm, but subsequently, by letter, we were advised that “18 patients (11 standard, 7 hemodynamic) who had systolic BP <140 mm Hg and diastolic BP <90 mm Hg at screening” were excluded because post-washout BP (which was higher) rather than screening BP had been used for selection. Two patients moved and were not further evaluated. The other 18 patients completed an average of 3.4 visits during the study. A chart indicated that if these patients were included in final analysis the 77 patients in the HC arm would have had an SBP change of -17±18 compared to -9±4 for the 105 patients in the standard arm. We have confirmed with the requestor that there was a transposition in the data presented in the letter regarding DBP change and that the correct information for the hemodynamic arm was -10±11 and -4±12 in the standard arm. Mean screening SBP for the 8 patients eliminated from the hemodynamic arm was 131 and mean DBP was 70. In the standard care arm for the 12 patients eliminated mean SBP was 126 and DBP 73. The trial was not an intention-to-treat analysis and data for these 20 patients were excluded from the published report of the trial. Authors offered no explanation for the 3:2 ratio of patients in the standard care group versus the ICG group, but the requestor advises by letter that: “(t)he larger number of patients in the standard arm of CONTROL was … done to increase the confidence that the standard arm results would reflect primary care results and would not be due to chance. This meant that significantly more patients were enrolled than would have been required for a trial with a 1:1 ratio”. Each of the 164 analyzable patients in the study had a total of five study visits at which BP and ICG measurements were made. Following a baseline visit they underwent a two week washout period during which all antihypertensive medications were discontinued. They received a post-washout visit at which physicians “prescribed medications consistent with published guidelines, their usual practice patterns, and patient clinical characteristics.” This was followed by three monthly visits at which BP was measured and ICG data were obtained on all patients, “but ICG findings were not revealed in the standard arm to treating physicians or patients.” In the hemodynamic arm, physicians were encouraged to use but not required to follow a hemodynamic treatment strategy (a simplified and somewhat modified version of the treatment algorithm proposed by Taler et al. (Taler SJ, Textor SC, Augustine JE, 2002). That “Hemodynamic Treatment Algorithm” is included in CMS’ August 3, 2003 “Decision Memorandum for Electrical Bioimpedance for Cardiac Output Monitoring.” No explanation for differences between the two treatment guides was offered in the published trial description. By letter, the requestor states: “The suggested medication choices based on hemodynamic data were very similar to the Mayo Clinic (Taler) algorithm except for the use of thoracic fluid content (TFC) with diuretics. Because diuretics are suggested first-line therapy in JNC guidelines, we did not want to suggest that TFC needed to be used to determine whether diuretics should be initiated. So, instead, the CONTROL hemodynamic treatment strategy suggested using visit-to-visit TFC changes as indicator of diuretic effectiveness. This is in contrast to the Mayo Clinic’s use of TFC as absolute indicator for intensification of diuretics. Since most of the patients in the Mayo Clinic trial were already on diuretics at baseline, it represented a different clinical scenario than the patients in CONTROL, many of whom were not on diuretics at baseline.” Data are not provided on adherence to the strategy or differences in outcomes within the hemodynamic group based upon adherence. The CONTROL study’s proposed treatment strategy for the experimental group, employing specific types of drugs to be prescribed based on hemodynamic data, is summarized in the table below. Hemodynamic Data Medication Choice* High Systemic Vascular Resistance Index Increase dose or add: ACEI, ARB, CCB, VD Low/Normal Cardiac Index Consider reduced dose BB Evaluate visit-to-visit Thoracic Fluid Content If diuretic previously added/increased and visit-to-visit Thoracic Fluid Content not reduced, consider increase/change: diuretic High Cardiac Index Increase dose or add: BB, CAA Normal Systemic Vascular Resistance Index Consider reduced dose: VD Evaluate visit-to-visit Thoracic Fluid Content If diuretic previously added/increased and Visit-to-visit Thoracic Fluid Content not reduced, consider increase/change: diuretic * ACEI: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CCB: calcium channel blocker; VD: vasodilator; BB: β blocker; CAA: central acting agent. Patients in both arms were educated about medication compliance and received a follow-up phone call from a nurse between visits. ICG data were discussed with the patient by the treating physician in the hemodynamic arm only. Patients were asked how many of their prescribed pills they had taken at each visit as an estimate of compliance. The authors report very high compliance overall, including 100% of pills taken in both arms of the trial at the 5 th visit. Pill count audits were not done. The study reports baseline characteristics for patients showing insignificant differences between groups, but some individual items are of interest for a Medicare decision. The mean age of participants is ~ 55 years, about a decade younger than the standard age of Medicare eligibility. Only 4% of the subjects had diabetes, whereas over 20% of adults 60 years and older have diabetes and the prevalence increases with advancing age. Presence of diabetes may affect both the intensity of treatment and the choice of medications in treating hypertension. No information is presented about non-pharmacologic lifestyle modifications that patients may have been prescribed to reduce BP, such as exercise, weight loss, smoking cessation, and decreased alcohol consumption, among others. Such modifications are considered first line therapy in beginning the treatment of hypertension, and generally only when they are unsuccessful are medications begun. Information is not provided about how long a patient had been under treatment for hypertension prior to study entry. A large percentage of both groups (42% of standard care group and 45% of hemodynamic care group) were on only one antihypertensive medication at baseline. Most guidelines on the treatment of hypertension suggest beginning drug treatment with a single medication (usually a diuretic) and adding additional medications, depending on patient characteristics and presence of comorbid conditions, until control is achieved. The number of patients (18/184 or 10%) excluded from the study after screening when it was found that their BP was <140/90 on repeat examination and the ~43% of study participants on only one medication would seem to indicate either very recently diagnosed disease or lack of intensive effort to control. At baseline, standard care (SC) patients’ BP (in mmHg.) was 147±9/87±10 and hemodynamic care (HC) patients’ BP was 148 ±12/89 ±8. After washout, SC BP was 156±13/92±9 and HC was 155±13/94±9. There were no statistically significant differences reported in any hemodynamic measures between the groups at baseline or after washout. The following table from the CONTROL study summarizes the major findings: Final BP and Hemodynamic Values Variable Standard Care (n=95) Hemodynamic Care (n=69) P Value Systolic BP, mmHg Final ∆ baseline to final ∆ post-washout to final 136 ± 15 -11 ± 18 -19 ± 17 129 ± 14 -19 ± 17 -25 ± 18 <0.01 <0.01 <0.05 Diastolic BP, mmHg Final ∆ baseline to final ∆ post-washout to final 82 ± 10 -5 ± 12 -10 ± 11 76 ± 11 -12 ± 11 -17 ± 12 <0.01 <0.001 <0.001 Heart rate, bpm Final ∆ baseline to final ∆ post-washout to final 77 ± 13 1 ± 12 -2 ± 13 76 ± 11 2 ± 13 -2 ± 13 ns ns ns Cardiac index, L/min/m² Final ∆ baseline to final ∆ post-washout to final 2.9 ± 0.5 0.1 ± 0.5 0.0 ± 0.5 2.9 ± 0.5 0.0 ± 0.5 0.0 ± 0.5 ns ns ns Systemic vascular resistance index, dyne x s x m²/cm² Final ∆ baseline to final ∆ post-washout to final 2714 ± 619 -219 ± 667 -369 ± 642 2523 ± 581 -433 ± 660 599 ± 738 <0.05 <0.05 <0.05 Thoracic fluid content, /kOhm Final ∆ baseline to final ∆ post-washout to final 27.8 ± 4.1 -0.8 ± 3.6 -1.2 ± 3.3 28.2 ± 4.9 0.1 ± 3.0 -0.2 ± 2.7 ns ns <0.05 The authors reported generalized information as to how hemodynamic data was used. Specific information as to how a particular hemodynamic measurement was used to change patient treatment was not provided. For example, “In the hemodynamic arm, the initial selection of antihypertensive medications appears to have been influenced by the hemodynamic data, because these patients were more likely to be prescribed a vasodilating agent to reduce SVRI” and “the hemodynamic treatment strategy influenced medication use when SVRI was considered high, because patients in the hemodynamic arm were more likely to have received an ACEI, ARB, or CCB, as was suggested.” The authors state “(i)n theory, the larger drop in SVRI and BP levels in the hemodynamic arm could have occurred through use of more medications, more effective medications, greater dosing intensity, more effective combination therapy, or better patient compliance. Our study allowed full discretion by the physician in choosing the agents, and a multitude of classes and doses within classes were used.” They further state the study “was designed to determine whether providing hemodynamic data to the physician and the patient could more effectively reduce BP. Whether hemodynamic data led to a more tailored approach to selection and monitoring of antihypertensive agents or by other factors, it resulted in greater reduction in BP and SVRI and better BP control,” Publication of the results of the CONTROL study in the April 2006 issue of Hypertension was accompanied by an editorial comment, “Noninvasive hemodynamic measurements an important advance in individualizing drug therapies for hypertensive patients.” (Flack JM, 2006) While the editorial finds the results of the study “encouraging” it points out that “practitioners did not follow the suggested treatment algorithm to add or increase diuretics when thoracic fluid content did not decrease in response to diuretic initiation or dose escalation” and “did not comply with all the suggested therapeutic decisions in the study treatment algorithm.” Flack lists a number of questions still to be answered relating to IC use in the management of hypertension: Does use of IC lead to more rapid control of BP through better pharmacologic choices? Does continued use of IC lead to prolonged BP control? How should multiple hemodynamic abnormalities be treated? Should hemodynamic abnormalities be treated even after normal BP is achieved? How quickly would IC be accepted? MCAC A Medicare Coverage Advisory Committee (MCAC) meeting was not convened on this issue. 5. Evidence-based guidelines CMS has not located any evidence-based guidelines for the use of TEB in the treatment of hypertension. 6. Professional Society Position Statements The American College of Cardiology (ACC) submitted a position statement during the first public comment period that is excerpted below. The entire letter may be viewed in Appendix B and at http://www.cms.hhs.gov/Medicare/Coverage/DeterminationProcess/downloads/id179a.pdf [PDF, 169KB] “Members of the ACC’s Heart Failure and Transplant Committee and Prevention Committee have reviewed the reconsideration request, along with the evidence submitted concerning use of thoracic electrical bioimpedance (TEB) in the management of patients with hypertension. We found that the evidence does not support establishment of national Medicare coverage as requested for hypertensive patients on one or more anti-hypertensive drugs who are not at goal blood pressure. Our clinical experts noted that the two small randomized studies cited by the requester focused only patients with blood pressure that was quite difficult to control. The patients were typically on multiple anti-hypertensive drugs and were, on average obese. These factors limit the extent to which the results of the studies can be generalized to the broader population of patients who have failed to achieve desired blood pressure control on only one or more antihypertensive drugs. The studies cited do provide some evidence of benefit for a more narrowly defined patient population. The ACC believes that Medicare coverage for patients with drug resistant hypertension, defined as failure to achieve goal blood pressure when adhering to full doses of an appropriate three drug regimen, including a diuretic may be appropriate. We note that the current NCD already provides local Medicare carriers with the explicit discretion to coverage TEB for this patient population”. The ACC submitted a second position statement during the second public comment period supporting their previous position, excerpt below. “We had previously found that the evidence offered for the first reconsideration was not sufficient to support establishment of national Medicare coverage as requested for hypertensive patients on one or more anti-hypertensive drugs who are not at goal blood pressure. At this time, the ACC has not been presented with sufficient evidence to alter this opinion as expressed in our previous comments on this NCA. We therefore support CMS’ proposed decision memorandum as written”. An additional position statement was received in the second public comment period from the International Society on Hypertension in Blacks (ISHIB) opposing our decision to maintain current TEB coverage and requesting extended coverage for TEB: “We therefore take the position that extending coverage nationally for impedance cardiography will ultimately lead to better patient care and fewer costly pressure related clinical outcomes because of improved therapeutic decision-making and, we posit, less therapeutic inertia. Thus, we support extending coverage for impedance cardiography to high-risk (diabetes mellitus and/or chronic kidney disease according to JNC 7 definitions) on at least 2 antihypertensive medications and to all other hypertensive patients taking at least three antihypertensive drugs”. Both of the above position statements received during the second comment period may be viewed in their entirety in Appendix B and at: http://www.cms.hhs.gov/Medicare/Coverage/DeterminationProcess/downloads/id179b.pdf [PDF, 1MB]. 7. Expert Opinion We have not currently received any expert opinions on the use of TEB for managing hypertension. 8. Public Comments Initial Comment Period: February 28, 2006 – March 30, 2006 CMS received 217 comments during the 30 day initial public comment period. Three commenters sent the same comment two times – accordingly, 214 comments were actually received. One comment received from the American College of Cardiology is discussed above in the Professional Society Position Statement section. One hundred eighty-eight comments (88%) were from physicians; 15 (7%) were from nurses, pharmacists, nurse practitioners, and physician assistants; and two commenters (1%) were family members. Nine commenters did not specify their relationship to the issue. No comments were received from persons identified as patients. Most of the public comments were personal experiences submitted by physicians using TEB in their office settings. Two hundred nine (98%) of these comments supported coverage of TEB for the assessment of hypertension in the outpatient setting. Four commenters opposed coverage of TEB and one commenter did not express an opinion. One commenter said that the existing CMS coverage is too expansive. No new published scientific evidence was submitted. Second Comment Period: August 24, 2006 – September 23, 2006 CMS received 254 comments during the 30 day second public comment period in response to our proposed decision memorandum. Two comments received from professional societies (American College of Cardiology and International Society on Hypertension in Blacks) are discussed above in the Professional Society Position Statement section. None of the other comments included additional medical literature for review. Two hundred twenty-eight comments (90%) were from physicians and other health practitioners; 22 (9%) were from Medicare patients, one comment each was received from a manufacturer of another cardiac device and a manufacturer’s trade association. Eleven of the physicians indicated they were representing group medical practices. The requestor’s revised coverage request was submitted in the form of a public comment and while it sought to add to and clarify data included in the published report of the CONTROL trial, it did not introduce new literature for review. Our response to these materials is incorporated into our revised discussion of the CONTROL trial. Comment on clinical use of TEB: Other than the American College of Cardiology comments described above, commenters opposed the proposed coverage decision. As during the previous public comment period, nearly all of the public comments were personal experiences submitted by physicians and others using TEB in their office settings. Many commenters suggested expanding TEB coverage by reducing the number of anti-hypertensive drugs required to obtain coverage. Nine commenters suggested coverage of TEB for patients on one antihypertensive medication, 125 suggested coverage for users of two or more drugs, five suggested three or more drugs, and 115 either expressed no opinion or were unclear in their suggested coverage. Response: In reviewing public comments we could find no consensus among medical professionals using the device as to when TEB was medically necessary or how often it needed to be repeated. None suggested either the quarterly schedule and yearly four test limitation or thirty day interval between tests suggested in the requestor’s recent letter. Nor did anyone suggest a 6 month attempt at BP control before using TEB. Some physicians appeared to use the device on every hypertensive patient, while others made the point that they used clinical judgment to determine when it could be useful. Frequency of use ranged from rarely on a purely clinical basis depending on experience with a particular patient to as often as 3 to 5 week intervals for up to 6 months, while adjusting medications to achieve goal BP. Not only did comments fail to support the Conditions and Frequency Limitation offered by the requestor in its September 23 revised request, but the nine comments supporting use when on one drug could be considered to be in opposition to the proposal. Comment on local Medicare contractor discretion: 150 commenters (59%) oppose the current policy of local contractor discretion for coverage of the use of TEB for drug resistant hypertension, mainly because some local Medicare contractors have chosen not to provide coverage. Response: Medicare contractors have statutory authority to develop local policy for their jurisdictions. Variation from jurisdiction to jurisdiction is clearly anticipated by and supported by statute. Comment on CMS’ interpretation of the evidence: Several comments questioned CMS’ interpretations of the Mayo Clinic and CONTROL trials. Some stated that the two trials showed improvements in BP control with TEB use and if the results are summed could be considered clinically impressive. Response: The Mayo Clinic trial was reviewed in a past reconsideration of this NCD and our detailed analysis of that trial may be found in the decision memorandum that accompanied that reconsideration. Our analysis of CONTROL is included in this decision memorandum. Comment on patient compliance: Several commentors made the point that having a printout of the TEB test results encouraged patient compliance with prescribed drugs and that when the test was repeated on subsequent visits patients had visual proof of the efficacy of their efforts to control BP. Response: We recognize that physicians may share test results with patients, whether they are derived from TEB, clinical laboratory, radiography or other modalities, in an attempt to motivate patients to comply more fully with recommended treatments. In the case of hypertension, the blood pressure measurement itself is a test result that is routinely shared with the patient at every visit. On October 17, 2006 we conducted an Ovid MEDLINE search using the following terms: Compliance/ or Patient Compliance/ limit 1 to (humans and English language) AND Pharmaceutical Preparations/ad [Administration & Dosage]. We did not find published research on whether compliance, when systematically accessed, is actually improved by the sharing of test results. That absence does not refute the possibility, it simply points to the current lack of evidence to support the anecdotal observations. VIII. CMS Analysis National coverage determinations (NCDs) are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally under title XVIII of the Social Security Act § 1869(f)(1)(B). In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B, and must not be otherwise excluded from coverage. Moreover, with limited exceptions the expenses incurred for items or services must be “reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.” §1862(a) (1) (A). This section presents the agency’s evaluation of the evidence considered and conclusions reached for the assessment question. Question Is the evidence sufficient to conclude that hemodynamic monitoring with thoracic electric bioimpedance (TEB), when used by the treating physician to guide management of the patient’s medical problem, improves health outcomes in Medicare beneficiaries with hypertension who are on one or more antihypertensive drugs and who are not at goal blood pressure? As a diagnostic test, hemodynamic monitoring would not be expected to directly change health outcomes. Rather, a diagnostic test affects health outcomes through changes in disease management brought about by physician actions taken in response to test results. Such actions may include decisions to treat or withhold treatment, to choose one treatment modality over another