K. S
EIDLIntroduction
Heart failure is a common condition with an estimated overall prevalence of 1–2%. Prevalence increases by age, with a marked rise above the age of 60 years [1, 2]. The progress in the pharmacological treatment of heart failure has been substantial [3, 4], but 1-year mortality is still around 10–14% [5, 6].
Healthcare expenditures for heart failure are significant, accounting for nearly 2% of the healthcare budget, 65–75% of which relates to hospital care [7, 8].
Patients with severe heart failure refractory to drug treatment can be offered heart transplantation or a cardiac assist device as a bridge to trans- plantation. Such treatment, however, is available for only a limited number of patients, so there is a clear need for additional treatment options.
It is estimated that 30% of patients with severe heart failure have intra- ventricular conduction disturbances characterised by wide QRS complexes and an uncoordinated ventricular contraction pattern [9, 10]. The delay in ventricular electrical activation may be overcome by biventricular pacing. A large number of uncontrolled and controlled randomised studies dealing with cardiac resynchronisation therapy (CRT) demonstrate improvements in central haemodynamics, exercise tolerance, and quality of life in patients with severe heart failure and wide QRS complexes [11–13].
The aim of the present study was to assess (1) the clinical effectiveness of a conventional individual optimised drug therapy for heart failure in com- parison to the combination of drug treatment plus biventricular pacing, and (2) to evaluate its cost-effectiveness in respect of hospitalisations and outpa- tient visits.
Herzzentrum Ludwigshafen, Ludwigshafen, Germany
Methods
Between January 1995 and December 2002, 1118 consecutive patients with heart failure were included in a left ventricular dysfunction registry. The inclusion criterion was an ejection fraction below 45%. Mean age was 65 ± 11 years, 78% of patients were male, and the mean ejection fraction was 29 ± 8%. The aetiology of left ventricular dysfunction was coronary artery disease in 65%, non-ischaemic cardiomyopathy in 31%, and hypertensive heart dis- ease in 4%. In this study population of 1118 patients, 97 patients received a CRT device because of severe heart failure which was refractory to optimised drug treatment (Table 1).
Table 1.Clinical data of patients included in the left ventricular dysfunction registry
LVD patients CRT patients
(n = 1021) (n = 97)
Age (mean ± SD, years) 65 ± 9 65 ± 8
Male gender (%) 78 87
Coronary artery disease (%) 66 39
Non-ischaemic cardiomyopathy (%) 29 61
Diabetes mellitus (%) 28 22
Arterial hypertension (%) 59 43
LVD, left ventricular dysfunction; CRT, cardiac resynchronisation therapy
Within this study population we performed a matched controlled study for inter-individual comparison between similar patient groups in respect of clinical and economic data. Patients were matched for age, ejection fraction, NYHA functional class, and follow-up duration of 18 months. Overall 42 patients were enrolled in this comparison study: 14 patients in the control group versus 14 patients in the CRT pacemaker versus 14 patients in the CRT implantable cardioverter–defibrillator (ICD) arm. In this inter-individ- ual comparison, cost-effectiveness was evaluated on the basis of the follow- ing data: symptoms, number of hospital stays, number of hospital days, and number of outpatient visits during a 12-month follow-up.
In addition, an intra-individual comparison was performed. For this pur-
pose the clinical and economic data regarding these patients were collected
for the entire year preceding the implantation and the year after implanta-
tion of a CRT device.
Results
Data for the patients of these three groups are shown in Tables 2 and 3. There was no significant difference in regard to age, gender, structural heart dis- ease, diabetes, hypertension, ejection fraction, and NYHA functional class.
However, there was a significant difference in QRS duration. Patients in the control arm had a mean QRS duration of about 107 ± 20 ms, patients in the CRT pacemaker arm had a mean QRS duration of 160 ± 23 ms, and patients in the CRT ICD arm had a mean QRS duration of 153 ± 40 ms.
During the 12-month period 71% of the patients in the control arm were in NYHA functional class III, 7% in NYHA class IV, and only 21% in NYHA class II. In contrast, during the same follow-up period 71% of the patients with the pacemaker were in NYHA class II, 21% remained in NYHA class III, and only 7% were in NYHA class IV. Similar results were obtained in the patients with the ICD: 79% of these patients were in NYHA class II, 14% in NYHA class III, and 7% in NYHA class IV (Fig. 1) during follow-up.
Table 2.Clinical data of patients in the inter-individual and intra-individual comparison groups
Control CRT pacemaker CRT ICD P value
(n = 14) (n = 14) (n = 14)
Age (mean ± SD, years) 66 ± 7 67 ± 5 67 ± 5 0.61
Male gender (n) 14 14 14 1
Coronary artery disease (n) 8 6 6 0.68
Non-ischaemic CMP (n) 6 8 8 0.28
Diabetes mellitus (n) 1 2 1 0.76
Arterial hypertension (n) 4 5 6 0.73
Ejection fraction (%) 24 ± 6 25 ± 6 24 ± 6 0.89
QRS duration (mean ± SD, ms) 107 ± 22 160 ± 23 153 ± 40 0.009
NYHA class II (n, %) 4, 29 1, 7 2, 14 0.63
NYHA class III (n, %) 9, 64 11, 79 10, 71
NYHA class IV (n, %) 1, 7 2, 14 1, 14
Table 3.Drug treatments in the inter-individual and intra-individual comparison groups
Control CRT pacemaker CRT ICD P value
(%) (%) (%)
Beta-blocker 67 67 71 0.67
ACE inhibitor 86 86 93 0.45
Diuretic 83 100 93 0.32
Digitalis 79 86 86 0.84
Inter-individual Comparison
During a follow-up of 12 months patients in the control group had 2.3 ± 1.8 hospital stays, versus 1.5 ± 1.9 hospital stays in the patient population with the ICD device and only 0.6 ± 0.9 hospital stays in the patient population with the pacemaker. These differences were significant (Fig. 2). In respect of the mean number of hospital days during the 12-month follow-up, patients in the control group had 24 ± 22 days in hospital; patients in the CRT/ICD arm had 16 ± 22 days in hospital versus only 12 ± 19 days for the patients in the CRT pacemaker arm (Fig. 3).
No differences were noted in the number of outpatients visits (Fig. 4).
Fig. 1a–c.NYHA functional class in the control group (a) and in the pacemaker (b) and ICD groups (c) before and after implantation
a
b
c
Intra-individual Comparison
The mean number of hospital stays in CRT pacemaker patients was reduced from 2.4 ± 1.7 stays before pacemaker implantation to 0.6 ± 0.9 hospital stays after implantation (Fig. 5). Similar results were obtained in patients with the ICD (Fig. 6): during the year before implantation the mean number of hospital stays was 2.9 ± 1.1, after CRT implantation 1.5 ± 1.9.
The mean number of hospital days was reduced in the year after CRT device implantation in comparison to the year preceding the implantation: in the pacemaker group from 23 ± 18 to 12 ± 19 days, in the ICD group from 42 ± 22 to 16 ± 22 days (Figs. 7, 8).
Fig. 2.Mean number (± SD) of hos- pital stays per patient in the three groups during 12-month follow-up
Fig. 3.Mean number (± SD) of days in hospital per patient in the three groups during 12-month follow-up
Fig. 4.Mean number (± SD) of out- patients visits per patient in the three groups during 12-month fol- low-up
The mean number of hospital stays and the mean number of hospital days during the year before CRT device implantation were similar and were in the same range as in the control group (2.3 ± 1.8 stays) (Figs. 5–8).
Fig. 5.Mean number (± SD) of hos- pital stays per patient in the control group and in the pacemaker group before and after implantation
Fig. 6.Mean number (± SD) of hos- pital stays per patient in the control group and in the ICD group before and after implantation
Fig. 7.Mean number (± SD) of days in hospital per patient in the con- trol group and in the pacemaker group before and after implantation
Fig. 8.Mean number (± SD) of days in hospital per patient in the con- trol group and in the ICD group before and after implantation
No differences were observed regarding outpatient visits in this study population (Figs. 9, 10). The important change after CRT implantation was the highly significant reduction in hospital stays and hospital days, which explained the cost reduction after CRT device implantation in this study.
Fig. 9.Mean number (± SD) of out- patients visits per patient in the control group and in the pacemaker group before and after implantation
Fig. 10.Mean number (± SD) of out- patients visits per patient in the control group and in the ICD group before and after implantation
Discussion
This study demonstrates a reduction in the need for hospitalisation and hos- pital days in parallel to clinical improvements by CRT in selected patients with severe heart failure. Similar findings were obtained by Braunschweig et al., which showed that the need for hospital care decreased significantly after biventricular pacing [14]. The total number of hospital days for all patients was 253 days in the year before versus 45 days in the year after biventricular pacing. For heart-failure-related hospital days the respective figures were 183 and 39 days. Biventricular pacing led to improvement in 13 of 16 patients with severe heart failure and wide QRS complexes in this open study. The improvement resulted in reduced need for hospital care.
In 2004, Dixon et al. demonstrated that CRT results in a significant
improvement in clinical parameters and considerable reductions in hospital
admissions and costs in patients with chronic heart failure [15].
In heart failure management it is essential to bring down the costs relat- ing to hospital care. Recent studies indicate that a comprehensive heart fail- ure care programme can reduce the need for hospital care [16]. In the pre- sent study all patients were recruited from a left ventricular dysfunction reg- istry with continued follow-up who still required a substantial amount of hospital care. We therefore believe that biventricular pacing rather than fre- quent follow-up was a reason for the improvement observed. Pacemaker therapy is not an inexpensive treatment and incurs costs for equipment, implantation procedure, and follow-up. The small number of patients does not justify more extensive cost–benefit analysis.
It is important to remember that it is hard to prove the cost-effectiveness of a novel treatment before it has been properly developed. For this reason, the pacemaker-related costs in the study were justifiable in view of the ongo- ing development and assessment of this treatment. In the future, the costs of biventricular pacing may be reduced as left ventricular lead technology is simplified and the patient selection improves. Nevertheless, these findings do indicate that CRT might reduce the costs for hospital care in selected patients with severe heart failure, at least over the first year. This treatment can therefore serve as a bridge to heart transplantation in those eligible, and improve the well-being and reduce the hospital care costs of these severely incapacitated patients [16].
The interpretation of our results is limited by the fact that the study was uncontrolled and enrolled only a small number of patients. Larger controlled studies are underway and will add valuable information to the issues dis- cussed above.
In this uncontrolled study, biventricular device therapy improved NYHA functional class and the clinical improvement was accompanied by a signifi- cantly reduced need for hospital care.
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