Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

BACKGROUND: INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. OBJECTIVES: This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. METHODS: Patients self-administered FlecIH over 8 minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. RESULTS: Mean age was 60.5 years, mean body mass index was 27.0 kg/m2, and 34.7% of the patients were women. All patients had ≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for ≤24 hours. The conversion rate was 42.6% (95% CI: 33.0%-52.6%) with a median time to conversion of 14.6 minutes. The conversion rate was 46.9% (95% CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. CONCLUSIONS: The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

[Dyspnoea due to ticagrelor after recent myocardial infarction]. / Dyspneu bij gebruik van ticagrelor na recent myocardinfarct.

BACKGROUND: Ticagrelor is a frequently prescribed platelet aggregation inhibitor used in patients with acute coronary syndrome. A rare side effect is severe dyspnoea. CASE DESCRIPTION: A 76 year old woman experiences severe shortness of breath three weeks after percutaneous coronary intervention because of acute myocardial infarction. Physical examination and additional investigation showed no pulmonary or cardiac explanation for her complaints. Shortly after cessation of ticagrelor, her complaints disappeared. CONCLUSION: Ticagrelor-related severe dyspnoea in post-myocardial infarction patients is a diagnosis by exclusion of other reasonable causes of dyspnoea. Unfamiliarity with this side effect can lead to excess diagnostics and unnecessary referrals.

Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction.

OBJECTIVE: We undertook a subgroup analysis of the On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2), a placebo-controlled, double-blind, randomised trial, in order to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and long-term (5 years) mortality and to investigate the effect of prehospital tirofiban administration on mortality in relation to NT-proBNP levels. METHODS: A total of 984 patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) were randomised to either in ambulance tirofiban or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hours thereafter (post PCI). RESULTS: There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post PCI. Patients with baseline NT-proBNP values above the median (137 pg/mL) had higher 30-day (5.1% vs 0.2%, p<0.001), 1-year (7.0% vs 0.7%, p<0.001) and 5-year (20.3% vs 4.9%, p<0.001) mortality as compared with patients with values below the median. Using multivariate Cox analysis, NT-proBNP above the median was an independent predictor for 5-year mortality (HR 2.73, 95% CI 1.47 to 5.06; p=0.002). Patients with values above the median who received early tirofiban treatment had significant lower mortality compared with patients treated with placebo at 30 days (2.7% vs 7.5%, p=0.021) and 1 year (4.5% vs 9.4%, p=0.043). At 5 years, a lower but non-significant mortality rate was maintained in the treatment group (18% vs 22.4%, p=0.265). CONCLUSIONS: In patients with STEMI, baseline NT-proBNP level independently predicts long-term mortality. In patients with baseline NT-proBNP levels above the median, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality, suggesting that high-risk patients may derive particular benefit. This finding should be confirmed in other studies. TRIAL REGISTRATION NUMBER: ISRCTN06195297.

Predictive value of NT-proBNP for 30-day mortality in patients with non-ST-elevation acute coronary syndromes: a comparison with the GRACE and TIMI risk scores.

BACKGROUND: The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts outcome in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Whether NT-proBNP has incremental prognostic value beyond established risk strategies is still questionable. PURPOSE: To evaluate the predictive value of NT-proBNP for 30-day mortality over and beyond the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores in patients with NSTE-ACS. METHODS: Patients included in our ACS registry were candidates. NT-proBNP levels on admission were measured and the GRACE and TIMI risk scores were assessed. We compared the predictive value of NT-proBNP to both risk scores and evaluated whether NT-proBNP improves prognostication by using receiver operator curves and measures of discrimination improvement. RESULTS: A total of 1324 patients were included and 50 patients died during follow-up. On logistic regression analysis NT-proBNP and the GRACE risk score (but not the TIMI risk score) both independently predicted mortality at 30 days. The predictive value of NT-proBNP did not differ significantly compared to the GRACE risk score (area under the curve [AUC]) 0.85 vs 0.87 p=0.67) but was considerably higher in comparison to the TIMI risk score (AUC 0.60 p<0.001). Adjustment of the GRACE risk score by adding NT-proBNP did not improve prognostication: AUC 0.86 (p=0.57), integrated discrimination improvement 0.04 (p=0.003), net reclassification improvement 0.12 (p=0.21). CONCLUSION: In patients with NSTE-ACS, NT-proBNP and the GRACE risk score (but not the TIMI risk score) both have good and comparable predictive value for 30-day mortality. However, incremental prognostic value of NT-proBNP beyond the GRACE risk score could not be demonstrated.

Association of serial high sensitivity troponin T with onset of atrial fibrillation in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

AIMS: Previous reports claimed that high sensitivity troponin T (HsTnT) is not associated with atrial fibrillation (AF) in the setting of acute ST-elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention. However, the association of serial HsTnT levels and new-onset AF is unknown. We therefore assessed the temporal association between HsTnT levels and post-infarction AF. METHODS AND RESULTS: 830 patients enrolled in On-TIME II were included. HsTnT was assessed at baseline, and 24h and 72 h after admission for STEMI. New-onset AF episodes were divided into three subgroups: AF during the first 24h of admission, AF 24-72 h after admission and AF >72 h after admission. ROC analysis and binary logistic regression were performed. Mean age was 62 ± 12 years and 76% were male. Seventy-three patients developed new-onset AF: 41 patients developed AF during the first 24h of admission, 14 patients developed AF 24-72 h after admission and 18 patients developed AF >72 h after admission. HsTnT at baseline was associated with new-onset AF (area under curve (AUC) 0.596, p=0.008), but not with AF during the first 24h of admission (AUC: 0.539, p=0.414). HsTnT after 24h (AUC 0.792, p=0.001) and after 72 h (AUC: 0.884, p<0.001) were associated with AF 24-72 h and >72 h after admission. HsTnT after 24h and 72 h were stronger predictors of AF compared with HsTnT at baseline. In regression analysis, age (odds ratio 1.056, p<0.001), Killip Class >1 (odds ratio: 2.694, p=0.010) and HsTnT after 24h (odds ratio: 1.012, p=0.017) and after 72 h (odds ratio: 1.035, p<0.001) showed the strongest association with post-infarction AF. CONCLUSION: Serial HsTnT plasma levels are associated with post-infarction, new-onset AF.

Early discharge after primary percutaneous coronary intervention: the added value of N-terminal pro-brain natriuretic peptide to the Zwolle Risk Score.

BACKGROUND: The Zwolle Risk Score (ZRS) identifies ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) eligible for early discharge. We aimed to investigate whether baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) is also able to identify these patients and could improve future risk strategies. METHODS AND RESULTS: PPCI patients included in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) II study were candidates (N=861). We analyzed whether ZRS and baseline NT-proBNP predicted 30-day mortality and assessed the occurrence of major adverse cardiac events (MACEs) and major bleeding. Receiver operating characteristic curve analysis was used to assess discriminative accuracy for ZRS, NT-pro-BNP, and their combination. After multiple imputation, 845 patients were included. Both ZRS >3 (hazard ratio [HR]=9.42; P<0.001) and log NT-pro-BNP (HR=2.61; P<0.001) values were associated with 30-day mortality. On multivariate analysis, both the ZRS (HR=1.41; 95% confidence interval [CI]=1.27 to 1.56; P<0.001) and log NT-proBNP (HR=2.09; 95% CI=1.59 to 2.74; P<0.001) independently predicted death at 30 days. The area under the curve for 30-day mortality for combined ZRS/NT-proBNP was 0.94 (95% CI=0.90 to 0.99), with optimal predictive values of a ZRS ≥2 and a NT-proBNP value of ≥200 pg/mL. Using these cut-off values, 64% of the study population could be identified as very low risk with zero mortality at 30 days follow-up and low occurrence of MACEs and major bleeding between 48 hours and 10 days (1.3% and 0.6%, respectively). CONCLUSION: Baseline NT-proBNP identifies a large group of low-risk patients who may be eligible for early (48- to 72-hour) discharge, whereas optimal predictive accuracy is reached by the combination of both baseline NT-proBNP and ZRS.

Predictors and importance of prolonged hospital stay after primary PCI for ST elevation myocardial infarction.

OBJECTIVE: Although most patients with ST-elevation myocardial infarction treated by primary percutaneous coronary intervention (PCI) have a good prognosis and can be discharged from hospital very soon, some patients must be admitted longer. We performed the current analysis to assess predictors and the prognostic significance of prolonged hospital stay. PATIENTS AND METHODS: In this prospective observational study, individual data from 2323 patients who survived at least 2 days after primary PCI in our hospital were recorded. Patients in the highest tertile of hospital stay were compared with the other patients. Both predictors and prognostic importance of prolonged hospital stay were evaluated. RESULTS: Mean admission duration was 6.7 days (standard deviation=6.6). A total of 797 patients had a hospital stay for more than 6 days (highest tertile). Patients with a longer hospital stay were older, more often female, had more often a history of previous myocardial infarction and signs of heart failure on admission, and had more frequently Thrombolysis in Myocardial Infarction flow 0 before PCI. In addition, a low left ventricular ejection fraction was independently associated with prolonged hospital stay [odds ratio: 2.06 (95% confidence interval: 1.54-2.76)], but with a comparable risk of 1-year mortality [odds ratio: 1.3 (95% confidence interval: 0.8-2.0)]. CONCLUSION: According to this study, a low left ventricular ejection fraction is associated with prolonged hospital stay in patients after primary PCI. Predictors of prolonged hospital stay are age, female sex, previous myocardial infarction, heart failure on admission, and Thrombolysis in Myocardial Infarction flow 0 before PCI.