Critical evaluation of the optimal medical therapy in the cardiac resynchronization therapy candidates – single centre experience

Summary

The aim of the present study was to evaluate the optimal medical therapy in the chronic heart failure (CHF) patients referred from the comunity centres and the outpatients cardiology clinics for the cardiac resynchronization therapy with defibrilator (CRTD) to the Department of Cardiology, Na Homolce Hospital with the device implantation between 1st January 2008 and 30st September 2009.

Methods:
The optimal medical therapy was analysed retrospectively from the medical records of 179 consecutive CHF patients NYHA class III–IV. Beta-blockers (BB) were used only in 81% subjects referred for CRTD, ACE inhibitors (ACEI) were used only in 68% patients Angiotensin receptor blockers (ARB) were used in 18 % subjects. ACEI or ARB were used in 81%, spironolacton was use in 59%. Recommended target DD for BB (carvedilol 25 mg bid) was used only in 13% subjects, recommended target DD for ACEI (enalapril 10 mg bid) was used only in 9.4% patients.

Results:
In the Department of Cardiology, the optimal medical therapy was changed after CRTD, BB were used in 95% subjects at discharge (p < 0.01) and the number of patients reaching at least of 50% of recommended daily dose (DD) of BB increased (p < 0.05). ACEI were recommended after CRTD in 80% subjects after implantation (p < 0.05), the number of patients reaching at least of 50% of recommended DD for ACEIs increased too (p < 0.05). There was no significant difference in ARB use recomended in the hospital (19%  after CRTD – NS). ACEI or ARB were used in 98% patients after the device implanted (p < 0.05) and spironolacton in 77% after CRTD (p < 0.05).

Conclusions:
Despite optimal composition of the optimal medical heart failure therapy only small number of CRTD candidates are reaching recommended drug dose. The optimization of the medical therapy in the specialized center lead to significantly higher proportion of CHF using the optimal therapy with the increased dose of BB and ACEI.

Key words:
chronic heart failure – cardiac resynchronization therapy – optimal medical therapy

Introduction

The cardiac resynchronization therapy (CRT) with automatic defibrilator (CRTD) improves outcomes in CHF patients NYHA class III and IV, with low LV EF, wide QRS complex and/or echocardiographic evidence of cardiac dyssynchrony [1]. CRTD also reduces morbidity and mortality in less symptomatic CHF patients NYHA class I and II with low LV EF ≤ 30% and QRS duration ≥ 130 ms [2]. The effectivity of device therapy is additional to optimal medical therapy, based on sympatoadrenal and renin-angiotensin-aldosteron (RAAS) blockade [2–9]. The reaching target drug dose is very often difficult because of the adverse symptomatic hypotension and bradycardia during up-titration of ACEI and BB. According to the results of CARE-HF study, ACEIs were used in 95% of patients and BB were used in about 70% of the patients treated with active CRT. The aldosteron blockade and digoxin was used in 54% and 40% of subjects in CARE-HF study [1].

Aim of the study

To evaluate the pharmacotherapy composition and the doses in the CRTD candidates referred to the Cardiocenter and to compare the medical therapy of the CRTD candidates from the referral units with a therapy after the device implantation at the specialized center.

Patients population

The pharmacotherapy was analysed retrospectively from medical records of 179 consecutive CHF patients (pts) NYHA class III and IV, referred for the first CRTD implantation to the Cardio­vascular Centre Na Homolce Hospital, Prague, Czech Republic between 1-Jan-2008 to 31-Aug-2009. The mean age of the subjects was 68.47 years, 21% of pts were women, 63% pts had coronary artery disease (CAD), the mean LV EF was 29.12%, the mean QRS duration was 155 msec and the cardiac dyssynchrony was identified in 32% of the pts. The patients characteristics are shown in the tab. 1.

Methods

The optimal medical therapy before and after the device implantation was obtained from the patients medical records retrospectively. The therapy composition and the daily drug dose were asessed in each subject. The mean daily dose (DD) of recommended drug therapy was calculated for the standard drug (calculated daily dose CDD). The daily dose of BB was calculated for carvedilol with target dose 50 mg daily, the daily dose of ACEI was calculated for enalapril with target daily dose 20 mg daily and the ARB daily dose was calculated for lo­sartan with target dose 50 mg daily. For the statistical analyses, unpaired t-test and McNamarra test were used with the level of significance p < 0.05.

Results

Beta-blockers (BB) were used in 81% subjects referred for the CRTD and in 95% at the discharge from the center (p < 0.01). The calculated daily dose (CDD) of carvedilol did not differ, but there was a significant increase in the number of the pts reaching at least of 50% of recommended DD (p < 0.02). ACE inhibitors (ACEI) were used in 68% patients before and in 80% subjects after the device implantation (p < 0.05). CDD for enalapril did not change, but there was a significant increase in the number of the pts reaching at least 50% of the recommended DD (p < 0.05). Angiotensin receptor blockers (ARB) were used in 18% subjects before and in 19% after the CRTD (N.S.). ACEI or ARB were used in 81% before and in 98% subjects after device implanted (p < 0.05). Spironolacton was use in 59% before and in 77% after the CRTD. The recommended target DD for BB (carvedilol 25 mg bid) was used only in 13% subjects before the device implanted, the target DD for ACE (enalapril 10 mg bid) was used only in 9.4% pts. The results are shown in tab. 2. Other therapy included: digoxin, furosemide or other diuretic, aspirin, warfarin, amiodarone, calcium channel blocker, allopurinol, statin and thyroid replacement therapy. The change of “other” medical therapy before and after CRTD is show in the tab. 3. The dose change of “other” medical therapy was not significant (N.S.). The daily dose of furosemide before CRTD was 67 mg and 59 mg after device implanted (N.S.). The daily dose for digoxin (mean 0,125 mg/day), aspirin (100 mg/day) and amiodarone (200 mg/day) was unchanged before and after CRTD.

Discussion

The resynchronisation therapy is indicated for the severely symptomatic CHF patients NYHA class III and IV, with the ischemic and non-ischemic etiology, with the LV dilatation and severe systolic LV dysfunction (LV EDD > 55 mm, LV EF ≤ 35%), and QRS duration ≥ 120 msec, when the standard medical therapy is not effective. The optimal CHF pharmacotherapy is based on the drug combination with the evidence of the improvement of morbidity and mortality. The optimal drug combination should be associated with the reaching of the recommended drug dose. The dose effect of BB and ACEI was documented in clinical trials [10–13]. The up-titration of BB and ACEI to the target doses is usualy limited by the adverse symptomatic hypotension and bradycardia.

Our present study showed, that only small proportion of CHF patients referred for the CRTD reached the recommended dose of BB and ACEI despite the optimal drug composition. The reason for this under-treatment might be the concern on the risk of symptomatic bradycardia or heart failure deterioration at BB up-titration. Cardiac pacing in CRTD candidates allows BB up-titration also in very symptomatic subjects NYHA class IV, the interval between dose doubling is usualy wider in the clinical practice. NYHA class III/IV patients with advanced CHF and low cardiac output also do not tolerate up-titration of ACEI/ARB therapy because of post dose symptomatic hypotension. This could be avoided with the low dose given in the afternoons or evenings. Another reason for not reaching recommended target drug dose might be also the fact, that not all CHF patients are followed by cardiologists trained in heart failure isssues.

After the CRTD, the optimal pharmacotherapy was introduced in the significantly higher proportion of CHF patients. After the CRTD, up to 95% patients were treated with BB, but with the low daily dose calculated for carvedilol 26 mg daily. All CHF patients should be treated with RAAS blockers too. In our study, the treatment with ACEI after the CRTD was initiated in the higher proportion of CHF subjects too, with the succesfull dose up-titration. But the daily dose calculated for enalapril was also low: 8.37 mg daily. The therapy with ACEI or ARB alternatively in ACEI intolerant subjects was reached in 98% of CHF patients after the CRTD activation. The dose of ARB should be definitely higher according to results of HEAAL study [13]. Thanks to these results we are changing our practice and we are recommending to have clinical visit of the CRTD candidates at the tertiary care heart failure clinic with check-up of the optimal medical therapy.

Conclusion

Despite the optimal composition of heart failure pharmacotherapy, the only small number of NYHA class III and IV patients refered for CRTD reached recommended drug dose before the device implantation. The optimal medical therapy introduced in the specialized center was given in the significantly higher proportion of the CHF pts with the increased BB and ACEI daily dose after resynchronization pacing started. CRTD candidates should be refered for the clinical evaluation to the specialized tertiary care heart failure clinics organized at cardiocentres in advance the device implantation.

Filip Málek, M.D., Ph.D., MBA

www.homolka.cz

e-mail: filip.malek@homolka.cz

Doručeno do redakce: 24. 12. 2010

Přijato po recenzi: 10. 3. 2011