The design of an observational study of hypertension management, adherence and pressure control in Blood Pressure Success Zone Program participants.

AIMS: The Blood Pressure Success Zone (BPSZ) Program, a nationwide initiative, provides education in addition to a complimentary trial of one of three antihypertensive medications. The BPSZ Longitudinal Observational Study of Success (BPSZ-BLISS) aims to evaluate blood pressure (BP) control, adherence, persistence and patient satisfaction in a representative subset of BPSZ Program participants. The BPSZ-BLISS study design is described here. METHODS: A total of 20,000 physicians were invited to participate in the study. Using a call centre supported Interactive Voice Response System (IVRS), physicians report BP and other data at enrolment and every usual care visit up to 12 +/- 2 months; subjects self-report BPs, persistence, adherence and treatment satisfaction at 3, 6 and 12 months post-BPSZ Program enrolment. In addition to BPSZ Program enrolment medications, physicians prescribe antihypertensive medications and schedule visits as per usual care. The General Electric Healthcare database will be used as an external reference. RESULTS: After 18 months, over 700 IRB approved physicians consented and enrolled 10,067 eligible subjects (48% male; mean age 56 years; 27% newly diagnosed); 97% of physicians and 78% of subjects successfully entered IVRS enrolment data. Automated IVRS validations have maintained data quality (< 5% error on key variables). Enrolment was closed 30 April 2007; study completion is scheduled for June 2008. CONCLUSIONS: The evaluation of large-scale health education programmes requires innovative methodologies and data management and quality control processes. The BPSZ-BLISS design can provide insights into the conceptualisation and planning of similar studies.

Thrombolysis in Myocardial Infarction frame count in saphenous vein grafts.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction flow grade system is a widely used index of coronary blood flow, it has important limitations. We recently described a new continuous measure of blood flow in native coronary arteries, the Thrombolysis in Myocardial Infarction frame count (TFC), and sought to extend this method to coronary artery bypass grafts. METHODS: We retrospectively analyzed cinefilms of patients' status after coronary artery bypass grafting, excluding patients with recent myocardial infarction and grafts with stenoses in the graft or native vessel. We counted the cineframes required for dye to travel from the ostium of the graft to the graft anastomotic site (TFCg) and to a standardized distal coronary landmark (TFC). RESULTS: For all vein grafts combined, TFCg was 19.2+/-5.7 frames (mean+/-SD, n = 93) and the TFC was 33.9+/-8.0 frames (n = 67). The upper limits for "normal" flow, calculated from the 95% confidence intervals, were 31 frames for TFCg and 50 frames for TFC. CONCLUSIONS: The Thrombolysis in Myocardial Infarction frame counting method has now been extended to normal saphenous vein grafts, and normal reference values are provided.

The Open Artery Hypothesis: Past, Present, and Future.

The survival benefit following a reperfusion strategy, be it pharmacologic or mechanical, appears to be due to both full and early reperfusion. While the TIMI Flow Grade classification scheme has been a useful tool to assess coronary blood flow in acute syndromes, it has several limitations. A newer method of assessing coronary blood flow called the Corrected TIMI Frame Count method has the following advantages: (1) it is a continuous quantitative variable rather than a categorical qualitative variable; (2) the flow in the non-culprit artery is not assumed to be normal as it is in the assessment of TIMI Grade 3 Flow; (3) there is simplified reporting of reperfusion efficacy through the use of a single number instead of expressing the data in 2 to 4 categories; (4) because a single number rather than 4 categories is used to report the data, there is more efficient use of the dataset by increasing the statistical power; and finally (5) coronary flow can be expressed in intuitive terms (e.g. time or cm/sec for strategy A versus time or cm/sec for strategy B). This paper reviews the history of the open artery hypothesis and recent advances in the field.

Streptokinase entrapment in interdigitation-fusion liposomes improves thrombolysis in an experimental rabbit model.

The successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis. First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase+empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p < 0.05) in the percent clot lysis were observed between saline control (22.4 +/- 3.3%; mean +/- S.E.), free streptokinase (36.3 +/- 3.4%), and liposomal streptokinase (47.4 +/- 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 +/- 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 +/- 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets. When tested in rabbits immunized against streptokinase, liposomal (33.8 +/- 1.5%) but not free streptokinase (29.3 +/- 2.1%) showed significant thrombolytic activity compared to saline (22.4 +/- 3.3%) (p < 0.05). The thrombolytic activity was comparable to free streptokinase in non-immunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.

Angioplasty guidewire velocity: a new simple method to calculate absolute coronary blood velocity and flow.

The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length divided by time) and absolute flow (area x velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) divided by TIMI frame count (frames) x film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm2) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 +/- 8.5 cm/s before to 22.8 +/- 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 +/- 5.4 to 23.5 +/- 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 +/- 0.4 ml/s before to 1.2 +/- 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 +/- 0.3 to 1.3 +/- 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.

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.