Following systematic searching of the named databases by two independent reviewers, 2352 articles were identified, totalling 1928 after removal of duplicates (Fig. 1). Title and abstract screening identified 12 articles that were potentially relevant to our review. Full text screening confirmed that six articles met our eligibility criteria, while the other six articles were excluded due to reasons detailed in Additional file 1:Appendix 2. Of the six articles that were included in analysis, five were randomized control trials (Cribier et al. 1995; Eltchaninoff et al. 1996; Ohman et al. 1994; Umeda et al. 2004; Zorger et al. 2002), and one was an institutional before-after trial (Arie et al. 1990). One study investigated femoropoliteal arterial interventions (Zorger et al. 2002), while the other five investigated coronary interventions. No study investigated cerebrovascular territories. The six studies included a total of 1496 procedures. While there was variation in study protocol between the prolonged inflation definition (60 to 900 s), there was more consistency between studies in the definition of brief inflation duration (30 to 60 s). Only the before-after trial (Arie et al. 1990) allowed for less than a 2:1 ratio in total initial inflation duration between prolonged and brief inflation. Four trials allowed for multiple inflations (Arie et al. 1990; Cribier et al. 1995; Eltchaninoff et al. 1996; Ohman et al. 1994), while the other two trials (Umeda et al. 2004; Zorger et al. 2002) only protocoled a single inflation. Study design and characteristics are summarized in Additional file 1: Appendix 3.
The immediate post-inflation radiologic and clinical outcomes are presented in Additional file 1: Appendix 4. The mean reported total balloon inflation times after all treatments ranged from 101 to 198 s and 238.8–973 s in the brief and prolonged inflation groups, respectively. Based on individual definitions of residual stenosis from each trial, which ranged from 30 to 50%, all studies noted a lower incidence and/or severity of residual stenosis in the prolonged inflation groups. Furthermore, all reporting trials noted less incidence of dissections in the prolonged inflation groups. Reporting of immediate clinical outcomes was inconsistent; however, three coronary trials noted an increased incidence of inability to tolerate the entire duration of balloon inflation in the prolonged inflation groups (Eltchaninoff et al. 1996; Ohman et al. 1994; Umeda et al. 2004).
Five trials (Arie et al. 1990; Eltchaninoff et al. 1996; Ohman et al. 1994; Umeda et al. 2004; Zorger et al. 2002) reported off-protocol adjunctive procedures performed after initial angioplasty, which consisted of either further balloon inflation or use of stent (Additional file 1: Appendix 5). The use of adjunctive procedures was less common in the prolonged inflation groups for each trial, and following adjunctive procedures, less residual stenosis was still observed in the prolonged angioplasty groups. It should be noted that no study blinded the operator to the group allocation, therefore decisions to perform adjunctive procedures were subject to potential bias.
Three studies (Eltchaninoff et al. 1996; Ohman et al. 1994; Umeda et al. 2004) also reported long-term outcomes, all in coronary arteries, and ranging from 4 to 12 months after the index procedure (Additional file 1: Appendix 6). All long-term anatomic surveillance was performed with angiogram and was performed on the majority (66% - 96%) of study participants in each trial. Although the incidence of stenosis during long-term follow-up was inconsistent among trials, all three reported a decrease in mean continuous severity of stenosis. Of note, no study defined how the index target lesion was identified, rather than further target vessel stenosis in a location other than the initial target lesion. Reporting of long-term clinical outcomes was inconsistent and did not specifically reference the preoperative status of individual patients.
Because the coronary vascular bed was the only vascular territory with multiple reported trials, statistical pooled analysis was performed within the coronary subgroup. Acceptable heterogeneity among reports of the primary outcome and several secondary outcomes in coronary arteries allowed for meta-analysis. The single peripheral vascular study is presented separate but alongside the pooled estimates of the coronary subgroup.
In the coronary studies, brief balloon inflation was significantly associated with greater risk of residual stenosis immediately post-inflation (RR 1.76 [95% CI 1.46–2.12], I2 = 0%, Fig. 2) and greater severity of residual stenosis (MD 2.99 [95% CI 1.21–4.76], I2 = 0%, Fig. 3). The single peripheral vascular study found a trend towards increased incidence of residual stenosis after brief inflation immediately post-inflation that did not reach significance (RR 2.40 [95% CI 0.94–6.13], p = 0.07).
In addition to residual stenosis, brief balloon inflation was also associated with greater risk of arterial dissection in the pooled coronary studies (RR 2.31 [95% CI 1.61–3.31], I2 = 0%, Fig. 4) as well as the single peripheral vascular study (RR 3.20 [95% CI 1.31–7.83]).
Clinically apparent end-organ ischemia during inflation was only reported in coronary studies, in the form of chest pain or ischemic ECG changes, and was significantly less common during brief angioplasty (RR 0.04 [95% CI 0.01–0.21], I2 = 0%, Fig. 5).
Off-protocol adjunctive procedures such as repeat angioplasty and/or stenting were more likely to be performed after brief inflation in the pooled coronary studies (RR 2.25 [95% CI 1.41–3.61], I2 = 24%, Fig. 6) as well as in the single peripheral study (RR 2.22 [95% CI 1.17–4.22]). Only coronary studies reported residual stenosis following adjunctive procedures at the completion of the procedure, which demonstrated a persistent increased risk of residual stenosis after initial brief inflation (RR 1.50 [95% CI 1.08–2.07], I2 = 0%, Fig. 7). Only three coronary studies (Eltchaninoff et al. 1996; Ohman et al. 1994; Umeda et al. 2004) reported long-term restenosis risks. Pooled analysis of these studies did not reveal a significantly increased risk of brief inflation on the binary presence of restenosis (RR 1.10 [95% CI 0.82–1.49], I2 = 67%, Fig. 8), however there was a benefit associated with prolonged inflation in reducing overall severity of stenosis (MD 3.18 [95% CI 0.43–5.92], I2 = 0%, Fig. 9).
Each study was assessed for risk of bias, which is summarized by the Cochrane Risk of Bias tool (Figs. 10 and 11). The before-after trial was at greatest risk of bias (Arie et al. 1990), however most trials may have been at risk of selection, reporting, and performance bias. The studies were also considered as individual units of analysis and plotted on a funnel plot, comparing the effect measure (risk ratio) of the primary outcome with an index of precision (Fig. 12). Using the overall pooled effect measure of the primary outcome as a reference, the paucity of low weight publications reporting relatively low effect measure was noted. This is potentially consistent with publication bias, but must also be interpreted with caution as only five studies reporting primary outcomes were included in this analysis. Sensitivity analysis investigating the effect of studies at high risk of bias and non-randomized trials did not reveal significant differences in the pooled effect estimates. Meta-regression could not be performed due to the low number of included trials.