Best of heart failure

48 vabradine was prescribed to was the indication to start ographics are shown in is study had adopted non- ., increase in salt and fluid vers, avoidance of precipi- d hypermobility syndrome hlers–Danlos syndrome. A f these 22 patients. ogram to exclude cardiac ty-four hour Holter moni- of the 22 patients (77%) rteen of the 22 patients other medication for POTS radine (Table 2 ). In four of ed to one other drug: flu- d midodrine in two patients. at the initial dosage of ses. It was titrated up to ntrol of symptoms. n 11 patients (50%). Mean p-titration was 9.5 (4.1) mg, se twice a day. EKGs after available for retrospective 9–17) months. Six patients 3 months. In four of them, wo for complete resolution ng of the symptoms of syn- 55 days). In one patient, patients ale 15, male 7 5 (11–17) years, 14.8 (1.6) years (4.1) mg, 0.1 mg/kg (0.9–17) months (0.9–17) months 5 (13.6) bpm .6 (20.2) ms , SD standard deviation G. D. Donne et al. management of the patients or the clinicians’ decision- making. The patients had all been prescribed the drug on a compassionate basis by their clinician and after potential benefits and side effects had been discussed with them and their parents. 2 Methods We evaluated patients younger than 18 years in our institution for whom ivabradine had been prescribed, from February 2008 to June 2014. We used our institutional pharmacy database. We ascertained the indication for starting the medication and in particular those where POTS was specified. POTS was defined as a sustained heart rate increase of 30 bpm or increase of heart rate to 120 bpm within the first 10 min of orthostasis associated with symptoms of orthostatic intolerance and without significant orthostatic hypotension [ 6 ]. Gender, weight, age at commencement, dose at commencement and after up-titration, reason for discontinuation, follow-up, days of treatment, medication prior to starting ivabradine, and medications with ivabradine, outcome (improvement, worsening of symptoms), heart rate and QTc at baseline and at follow-up were evaluated. Heart rate and electro- cardiogram (EKG) were recorded before starting ivabra- dine and at follow-up. 2.1 Statistical Analysis Normally distributed data were described with the mean and standard deviation (SD), whereas non-parametric data were described with median and range. Student’s inde- pendent t test was used as appropriate. A statistically sig- nificant level was set at p \ 0.05. 3 Results From the pharmacy database, ivabradine was prescribed to 28 children \ 18 years; POTS was the indication to start ivabradine in 22. Their demographics are shown in Table 1 . All patients included in this study had adopted non- pharmacological therapies (e.g., increase in salt and fluid intake, counter pressure maneuvers, avoidance of precipi- tating factors). One (4.5%) had hypermobility syndrome and three (13.6%) confirmed Ehlers–Danlos syndrome. A tilt test was performed in all of these 22 patients. All 22 had an echocardiogram to exclude cardiac structural abnormalities. Twenty-four hour Holter moni- toring was performed in 17 of the 22 patients (77%) showing no arrhythmia. Fourteen of the 22 patients (63.6%) were on at least one other medication for POTS prior to the introduction of ivabradine (Table 2 ). In four of 22 (18%), ivabradine was added to one other drug: flu- drocortisone in two patients and midodrine in two patients. Ivabradine was prescribed at the initial dosage of 5 mg/day in two divided doses. It was titrated up to 15 mg/day according to the control of symptoms. Ivabradine was up-titrated in 11 patients (50%). Mean (SD) dose of ivabradine after up-titration was 9.5 (4.1) mg, corresponding to 0.1 mg/kg/dose twice a day. EKGs after commencing ivabradine were available for retrospective analysis in 19 patients. 3.1 Follow-Up and Outcome Median follow-up was 4.6 (0.9–17) months. Six patients were followed up for less than 3 months. In four of them, ivabradine was discontinued: two for complete resolution of symptoms, one for worsening of the symptoms of syn- cope and palpitation (after 55 days). In one patient, Table 1 Demographics and the clinician’s stat d indications for starting ivabradine POTS 22 patients Gender Female 15, male 7 Age at commencement, median (range) and mean (SD) 14.5 (11–17) years, 14.8 (1.6) years Dose after up-titration mean (SD), absolute and per kg 9.5 (4.1) mg, 0.1 mg/kg Follow-up median (range) 4.6 (0.9–17) months Duration of treatment median (range) 3.7 (0.9–17) months EKG available for retrospective analysis (number of patients) 19 Holter 24-h monitoring (number of patients) 17 Echocardiogram (number of patients) 22 Tilt test (number of patients) 22 Baseline heart rate, mean (SD) 82.5 (13.6) bpm Baseline QTc, mean (SD) 397.6 (20.2) ms EKG electrocardiogram, POTS postural orthostatic tachycardia syndrome, SD standard deviation 60 G. D. Donne et al. management of the patients or the clinicians’ decision- making. The patients had all been prescribed the drug on a compassionate basis by their clinician and after potential benefits and side effects had been discussed with them and their parents. 2 Methods We evaluated patients younger than 18 years in our institution for whom ivabradine had been prescribed, from February 2008 to June 2014. We used our institutional pharmacy database. We ascertained the indication for starting the medication and in particular those where POTS was specified. POTS was defined as a sustained heart rate increase of 30 bpm or increase of heart rate to 120 bpm within the first 10 min of orthostasis associated with symptoms of orthostatic intolerance and without significant orthostatic hypotension [ 6 ]. Gender, weight, age at commencement, dose at commencement and after up-titration, reason for discontinuation, follow-up, days of treatment, medication prior to starting ivabradine, and medications with ivabradine, outcome (improvement, worsening of symptoms), heart rate and QTc at baseline and at follow-up were evaluated. Heart rate and electro- cardiogram (EKG) were recorded before starting ivabra- dine and at follow-up. 2.1 Statistical Analysis Normally distributed data were described with the mean and standard deviation (SD), whereas non-parametric data were described with median and range. Student’s inde- pendent t test was used as appropriate. A statistically sig- nificant level was set at p \ 0.05. 3 Results From the pharmacy database, ivabradine was prescribed to 28 children \ 18 years; POTS was the indication to start ivabradine in 22. Their demographics are shown in Table 1 . All patients included in this study had adopted non- pharmacological therapies (e.g., increase in salt and fluid intake, counter pressure maneuvers, avoidance of precipi- tating factors). One (4.5%) had hypermobility syndrome and three (13.6%) confirmed Ehlers–Danlos syndrome. A tilt test was performed in all of these 22 patients. All 22 had an echocardiogram to exclude cardiac structural abnormalities. Twenty-four hour Holter moni- toring was performed in 17 of the 22 patients (77%) showing no arrhythmia. Fourteen of the 22 patients (63.6%) were on at least one other medication for POTS prior to the introduction of ivabradine (Table 2 ). In four of 22 (18%), ivabradine was added to one other drug: flu- drocortisone in two patients and midodrine in two patients. Ivabradine was prescribed at the initial dosage of 5 mg/day in two divided doses. It was titrated up to 15 mg/day according to the control of symptoms. Ivabradine was up-titrated in 11 patients (50%). Mean (SD) dose of ivabradine after up-titration was 9.5 (4.1) mg, corresponding to 0.1 mg/kg/dose twice a day. EKGs after commencing ivabradine were available for retrospective analysis in 19 patients. 3.1 Follow-Up and Outcome Median follow-up was 4.6 (0.9–17) months. Six patients were followed up for less than 3 months. In four of them, ivabradine was discontinued: two for complete resolution of symptoms, one for worsening of the symptoms of syn- cope and palpitation (after 55 days). In one patient, Table 1 Demographics and the clinician’s stated indications for starting ivabradine POTS 22 patients Gender Female 15, male 7 Age at commencement, median (range) and mean (SD) 14.5 (11–17) years, 14.8 (1.6) years Dose after up-titration mean (SD), absolute and per kg 9.5 (4.1) mg, 0.1 mg/kg Follow-up median (range) 4.6 (0.9–17) months Duration of treatment median (range) 3.7 (0.9–17) months EKG available for retrospective analysis (number of patients) 19 Holter 24-h monitoring (number of patients) 17 Echocardiogram (number of patients) 22 Tilt test (number of patients) 22 Baseline heart rate, mean (SD) 82.5 (13.6) bpm Baseline QTc, mean (SD) 397.6 (20.2) ms EKG electrocardiogram, POTS postural orthostatic tachycardia syndrome, SD standard deviation 60 G. D. Donne et al.