Quality of life and symptoms in patients selected for ablation of ventricular extrasystoles: a prospective study.

PURPOSE: Evaluation of the impact of catheter ablation for ventricular extrasystoles (VES) in structurally normal hearts on quality of life (QOL) and symptomatology. METHODS: Symptom analysis assessed with a disease-specific questionnaire, EHRA score for AF, and QOL analysis at baseline and 1 year after ablation. RESULTS: The study enrolled 39 patients between April 2016 and November 2019. Two patients were excluded from further analysis. At baseline, palpitations were reported in 31/37 (84%); syncope in 12/37 (32%); other cardiac symptoms in 33/37 (89%) of patients. The EHRA score was 3 or 4 in 13 patients (35%). With the modified arrhythmia-specific questionnaire (MASQ) psychological and physical scores were 46 and 39%. The overall perception of health in the SF-36 was 56 ± 16%. Ablation was performed in 35/37 (95%). At regular follow-up, symptoms were reported in 14/37 (38%) patients. ECG suggested a good procedural outcome in 65% with VES burden on Holter < 1% in 68%. At follow-up, palpitations were reported in 61% (P < 0.07); syncope in only 1 patient (P < 0.05). The EHRA score was 3 or 4 in only one patient (P < 0.05). MASQ scores improved to 62 and 60% (both p < 0.001). The overall perception of health in the SF-36 became 64 ± 17% (P < 0.02). CONCLUSIONS: Patients with VES suffer from a wide variety of symptoms and have a low quality of life, as demonstrated by the EHRA score and conventional questionnaires. After catheter ablation, palpitations are still reported, but become less frequently present. Syncope becomes rare. Quality of life improves significantly from all perspectives.

Are ACE-inhibitors or ARB's still needed for cardiovascular prevention in high risk patients? Insights from profess and transcend.

The HOPE and EUROPA clinical studies have shown that treatment with the angiotensin-converting enzyme (ACE) inhibitors, ramipril and perindopril, may reduce the occurrence of major cardiovascular events in patients with proven atherosclerotic disease. The recently published results of the PRoFESS and TRANSCEND trials completed the much needed information concerning the use of an angiotensin receptor blocker for patients at high risk of cardiovascular events. PROFESS compared a therapy of telmisartan 80 mg daily with placebo in patients with a recent ischemic stroke. The difference in the primary outcome of first recurrent stroke was not statistically significant between telmisartan and placebo. The secondary outcome of major cardiovascular events showed a relative risk reduction (RRR) of 7% in favour of telmisartan. This tended to be significant (p = 0.06) despite a rather short follow-up period of only 28 months. In TRANSCEND 5926 patients at high risk for cardiovascular events were randomized to a treatment with telmisartan 80 mg daily or placebo for a mean duration of follow-up of 56 months. The primary composite outcome of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure showed a non-significant 8% RRR in favour of the telmisartan treated patients. The main secondary outcome of cardiovascular death and myocardial infarction or stroke as used in the HOPE trial showed a non-significant RRR of 13% in favour of telmisartan treated patients (p = 0.068 adjusted for multiplicity of comparisons). In comparing the Kaplan-Meier curves for the endpoint of major cardiovascular events used in HOPE, EUROPA, TRANSCEND and PRoFESS, the trends are similar. Results of most of the recently published trials have been neutral.This could partly be explained by major improvements in the optimal background therapy of the patients included. Nevertheless, the results of PRoFESS and TRANSCEND do not contradict the results from previous studies with theACE inhibitors ramipril and perindopril and the ARB telmisartan.

Lessons from ONTARGET.

The recently published results of the ONTARGET trial shed a new light on the cardiovascular protection of patients at high risk of a cardiovascular event. Despite a number of trials looking at the efficacy of Angiotensin Converting Enzyme inhibitors (ACEis) or Angiotensin Receptor Blockers (ARBs) in the prevention of cardiovascular events in patients with specific high risk profiles, the question of the equivalence of ACEis and ARBs remained unanswered. The ONTARGET trial has shown that telmisartan 80 mg administered for a median duration of 4.5 years to patients at high risk of developing a major cardiovascular event, is equally effective to ramipril 10 mg. In addition, telmisartan was slightly better tolerated. The comparator ramipril has been chosen as it is currently the gold standard ACEi since the results of the HOPE study, in terms of the composite outcome of cardiovascular death, myocardial infarction and stroke. Moreover, ONTARGET is the first trial to test the hypothesis of superiority of adding an ARB (telmisartan 80 mg) to an ACEi (ramipril 10 mg) over the ACEi ramipril monotherapy in cardiovascular protection of the same broad range of high-risk patients. Surprisingly, despite a more pronounced blood pressure lowering, the combination of the two agents did not lead to an additional decrease in the number of events, but had significantly more side-effects compared to ramipril monotherapy. ONTARGET is a landmark study, performed according to the highest statistical and clinical standards, providing compelling evidence and clear answers to two important clinical questions.

Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of 'Dear Doctor' letters.

PURPOSE: 'Dear Doctor' letters alert the prescribing community of drug labeling changes that contain new contraindications, warnings, adverse reactions, and precautions. There has been little assessment of the impact of these letters. We quantified the impact of two 'Dear Doctor' letters concerning interactions between cisapride and a series of drugs. A letter in 1995 described a risk of prolonged QT intervals and serious ventricular arrhythmia in patients who received macrolide antibiotics and imidazole antifungals in conjunction with cisapride. A June 1998 letter that expanded the list of contraindicated comedications had wider distribution than an earlier one, was accompanied by substantial Internet and media coverage, and was complemented by an effort to inform large pharmacy dispensing information organizations of the warnings against concurrent use of the named drugs. METHODS: Health plan members with one or more outpatient pharmacy claims for cisapride during the period 1 January 1995 through 31 May 1999 were identified among members of a large New England health insurer. A retrospective review of concurrent and nearly concurrent dispensings of cisapride and contraindicated comedications was undertaken in the automated pharmacy claims data using both graphical and statistical time-series analysis. We tabulated by month the fraction of cisapride dispensings that occurred in close temporal relation to dispensings of contraindicated comedications. Codispensings that occurred on the same day were taken as the most direct measure of prescriber responsiveness to the letters. Codispensings that occurred in windows of plus or minus 2 weeks (29 day window) and plus or minus 4 weeks (57 day window) were taken as measures of possible simultaneous consumption. Among overlapping dispensings, we counted the proportion dispensed by the same pharmacy. Time series regression analysis of secular, seasonal, and step-effects was conducted. RESULTS: There was a steady decline in codispensing of cisapride and contraindicated medicines, and a pronounced seasonal effect, arising principally from the seasonal use of macrolide antibiotics. Against this background, the isolated Dear Doctor letter of October 1995 had no discernible effect on prescribing practices. The 1998 letter and surrounding activity, by contrast, were followed by a 66% decline in same-day dispensings and a smaller, but still pronounced decline in dispensings in the wider time windows. For most codispensings of contraindicated medications with cisapride, both medications came from the same pharmacy. CONCLUSIONS: Publicity and direct intervention with dispensing pharmacies may be an important supplement to Dear Doctor letters when the goal is to eliminate the codispensing of drugs that should not be taken together.

Reproducibility of QTc-measurements in healty volunteers.

To assess the potential time-dependency and the reproducibility of the QTc-interval, ECG's from 84 healthy volunteers, recorded between 8 a.m. and 4 p.m., were analyzed. QT and RR intervals of all ECG's were measured by the same observer and Bazet's formula was used to correct QT intervals. The QTc-value showed a diurnal rhythm; its duration being minimal at 10 a.m., after which is gradually returned to the 8 a.m. value by 4 p.m. The 10 and 12 a.m. QTc's were statistically significantly shorter than the 8 a.m. QTc-interval (p < 0.05). There was not circannual rhythm. There was marked QTc-variability within one day, irrespective of the time at which the ECG had been obtained. Similar QTc-variability was also observed after longer intervals (week(s) or month(s)).

QTc-measurements: a case-control study on serum electrolytes.

This is a report on a prospective case-control study, in which a group of patients with an electrocardiographic diagnosis of QTc-prolongation (cases) was compared with a group of patients with a normal QTc (controls) for the presence of potential causative factors. Twelve cases and twelve carefully-matched controls were entered during a 1-year recruitment period. Ventricular arrhythmias were more frequent amongst the cases than amongst the controls (7/12 the cases, only 2/12 controls). Blood was sampled around the time of the ECG-recording in all patients. Forearm exercise (pumping) to increase venous blood pooling was prohibited before this blood sampling. The serum cation levels (potassium, calcium, magnesium) were determined in one central laboratory. Serum potassium levels were inversely correlated with the QTc-interval. Such a correlation was not found for the other two cations, although calcium levels also tended to be lower in patients with a long QTc. The findings, in addition, suggest that serum potassium values in the lower normal range (i.e. < 4 meq/l) might predispose to the development of ventricular arrhythmias. In view of these results, the diagnostic work-up of a patient with a long QTc is incomplete without a serum--K+, and possibly serum--Ca2+, assessment.