Terry Fortin

TIMI Frame Count A Quantitative Method of Assessing Coronary Artery Flow

BACKGROUND Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. METHODS AND RESULTS In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7 +/- 3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2 +/- 2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4 +/- 3.0) and circumflex counts (22.2 +/- 4.1, P < .001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2 +/- 20.0 frames, which improved to 31.7 +/- 12.9 frames by 18 to 36 hours (P < .001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (r=-.05, P=.59). The mean 90-minute CTFC among nonculprit arteries (25.5 +/- 9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0 +/- 3.1, P < .001) but improved to that of normal arteries by 1 day after thrombolysis (21.7 +/- 7.1, P=NS). CONCLUSIONS The CTFC is a simple, reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.

A Comparison of Quality of Life Scores in Patients With Angina Pectoris After Angioplasty Compared With After Medical Therapy Outcomes of a Randomized Clinical Trial

Background Evaluations of therapy for the treatment of angina have traditionally consisted of a combination of objective measures, such as exercise tolerance, and subjective markers, such as angina attack rate. Recently, the need to assess how patients feel-their quality of life (QOL)-has been regarded with increasing importance. Standard instruments are available to assess QOL and its change after therapeutic intervention. Although QOL instruments have been used to assess the efficacy of percutaneous transluminal coronary angioplasty (PTCA), they have not been used previously to compare the impact of PTCA with that of medical therapy in patients with angina pectoris. We report on the changes in self-assessed QOL among patients randomly assigned to treatment by PTCA or medical therapy and relate these measurements to changes in exercise performance and coronary angiograms. Methods and Results Patients with stable angina, a positive exercise tolerance test, and at least 70% stenosis (index lesion) in the proximal two thirds of one major coronary artery were randomly assigned to receive PTCA or medical therapy. Six months after randomization, each patient underwent repeat exercise testing and coronary angiography. Before randomization and at the 6-month visit, patients completed a self-administered QOL questionnaire that measured physical functioning and psychological well-being. We compared the changes in QOL with changes between the baseline and 6-month exercise tests, stratified by terciles (decrease in duration, 0- to 2-minute increase, and >2-minute improvement). We also stratified patients by whether there was more or less than 2 SD change (18.8%) in diameter stenosis of the index lesion (initial minus follow-up angiogram), and we related these to changes in QOL measures. One hundred eighty-two patients with one-vessel disease completed baseline and 6-month questionnaires. At baseline, there were no differences in any QOL measurements between treatment groups. At the 6-month follow-up visit, there was greater improvement in both physical functioning and psychological well-being scores for patients receiving PTCA (+7.36±15.6, PTCA ; +1.98±14.7, medical therapy; P<.02). Improvement in QOL variables was noted only in patients demonstrating an increase in exercise performance. Also, patients assigned to either treatment whose angiograms demonstrated more than 18.8% improvement in index lesion percent stenosis experienced a significant increase in their QOL scores. Conclusions This was the first study of the relative changes in QOL measures assessed with the use of previously validated and standardized instruments in patients randomly assigned to treatment with PTCA or medical therapy. Patients assigned to PTCA demonstrated a significantly greater improvement in both physical and psychological measures. This improvement was noted in patients whose exercise performance improved and whose angiograms demonstrated an improvement in lesion severity. (Circulation. 1995 ;92 :1710-1719.)

Safety and Tolerability of High-dose Inhaled Treprostinil in Pulmonary Hypertension.

Abstract: Pulmonary arterial hypertension (PAH) has emerging therapeutic options including prostacyclin analogs. Inhaled therapy offers advantages compared with alternative routes of administration. We aimed to determine the safety and tolerability of inhaled treprostinil (iTRE) titrated to target maintenance dose higher than the labeled dose for PAH. Our study included 80 consecutive patients (69% female, 70% White) followed at the Duke University Medical Center prescribed iTRE at dose >9 breaths (54 &mgr;g). Etiology of pulmonary hypertension was most frequently PAH (51%) or secondary to lung disease (35%). Median follow-up was 20.3 months (interquartile range 14.2–33.2). Most patients (91%) had titrated iTRE dose to 12 breaths (72 &mgr;g) four times daily. Common side effects reported with drug initiation were cough (41%), headache (28%), and throat irritation (8%); most of the side effects improved at follow-up. Overall, 25% patients discontinued iTRE: 9 transitioned to parenteral therapy, 4 had untolerable side effects, 3 died, and 4 had other reasons. Overall, iTRE taken at a higher dose than approved for use in PAH was safe and well-tolerated in our cohort of pulmonary hypertension patients.

SAFETY AND TOLERABILITY OF TRANSITION FROM INHALED TREPROSTINIL TO ORAL SELEXIPAG IN PULMONARY ARTERIAL HYPERTENSION: RESULTS FROM THE TRANSIT-1 STUDY

BACKGROUND A long-term trial showed that the oral prostacyclin (PGl2) receptor (IP) agonist, selexipag, delayed disease progression in patients with pulmonary arterial hypertension (PAH). Transition to selexipag in patients treated with more burdensome inhaled therapies that target the prostacyclin pathway may be considered by patients and physicians. The Phase 3b, prospective, open-label TRANSIT-1 (Tolerability and Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension) study evaluated the safety and tolerability of transition from inhaled treprostinil to oral selexipag. METHODS Patients receiving non-prostanoid oral PAH therapy and inhaled treprostinil at stable doses, in World Health Organization Functional Class II/III, with 6-minute walk distance ≥ 300 meters were enrolled. The 16-week main treatment period included downtitration of inhaled treprostinil over 8 weeks and parallel uptitration of selexipag over 12 weeks. Sustained treatment transition at Week 16 was defined as (1) receiving selexipag at Week 16; (2) no selexipag interruption(s) totaling ≥ 8 days; and (3) no inhaled treprostinil or other prostanoids after Week 8. Clinical parameters and patient-reported treatment satisfaction outcomes were assessed at Week 16. RESULTS All 34 enrolled patients completed the study. At Week 16, 32 patients (94.1%) had stopped inhaled treprostinil and were receiving selexipag. Twenty-eight patients (82.4%) met all criteria for sustained treatment transition. During the study, 3 patients discontinued selexipag due to adverse events. Overall, most adverse events were typical of prostanoid therapies and started during the uptitration phase. In general, patients remained clinically stable throughout treatment and reported improved convenience. CONCLUSIONS Transition to oral selexipag from inhaled treprostinil in PAH patients was successful and well tolerated in most patients, and associated with greater convenience. CLINICAL TRIAL NUMBER NCT02471183.