2.1

Protocol implementation and data sources

Data from the National Cardiovascular Data Registry® (NCDR) Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With the Guidelines™ (ACTION Registry–GWTG) from two tertiary care STEMI receiving centers (University of Pittsburgh Medical Center Presbyterian and Passavant Hospital) in the United States that are utilizing RIPC during inter-facility helicopter transport of STEMI patients for pPCI were used for this study. The ACTION Registry–GWTG is a nationwide, voluntary, quality improvement registry sponsored by the American College of Cardiology and the American Heart Association . The conduct of the RIPC protocol during helicopter transport of STEMI patients transferred to our two receiving facilities has been previously published . In summary, RIPC was performed during inter-facility helicopter transport by repeated 5-min cycles of inflation to 200 mmHg and deflation of a blood pressure cuff in the upper arm. A maximum of four cycles of RIPC were performed en route, and standard medical care for these patients and timeliness of transport were prioritized over RIPC. The protocol was approved by the University of Pittsburgh Institutional Review Board, the Pennsylvania Department of Health, the state EMS advisory council, and the regional Emergency Medical Services (EMS) council.

2.2

Patient population

Patients with STEMI (n = 536) that presented to the two PCI centers for pPCI from March 2013 through September 2015 were identified. Analyses were limited to STEMI patients with inter-facility air transport within the period that the RIPC quality improvement protocol was implemented. The protocol was first implemented at two air medical base sites as a pilot and then extended to 12 additional base sites, resulting in a cohort of patients that did or did not receive RIPC. STEMI was defined as chest pain or epigastric pain for more than 30 min and either (a) new ST elevation at the J point in two contiguous leads with the cut-off points of ≥0.2 mV in men or ≥0.15 mV in women in leads V2-V3 or ≥0.1 mV in all other leads or (b) new or presumed new left bundle branch block on electrocardiogram. Patients were excluded if they arrived directly to the emergency department of the two PCI centers (n = 88), were transferred from the field directly to the two PCI centers (n = 177), were transported by ground ambulance (n = 49), and those with persistent hypotension at the time of air transport (n = 3) were excluded. These patients were excluded because during the period of this study RIPC was not routinely performed in this EMS system for those transferred by ground ambulance and those with hypotension at the time of transfer. Additionally, those transferred from the field were excluded because the current analysis is limited to inter-facility transfers where multiple cycles of RIPC can be performed during transfer of the patients without delaying pPCI at the receiving facility. Given that patients with reduced LVEF are more likely to develop clinical HF symptoms, those with LVEF ≥55% (n = 69) were excluded from 219 inter-facility STEMI patients. The final population (n = 150) included in this analysis were inter-facility STEMI patients that were transported by air ambulance, received coronary stenting or plain old balloon angioplasty, and with LVEF <55% after pPCI.

2.3

Study outcomes

The main study outcome measure was the occurrence of clinical HF, defined as physician report of one or more of the following: i) unusual dyspnea on exertion or dyspnea occurring in the supine position; ii) rales or jugular venous distention on physical examination; and iii) pulmonary edema on chest x-ray presumed to be due to cardiac dysfunction. The other outcome measure was the first BNP level during hospitalization. These definitions were based on predefined criteria outlined in the ACTION Registry®–GWTG™ database. For outcomes analyses, we report i) the percentage of patients who experienced in-hospital clinical HF, and ii) the median BNP value.

2.4

Data analysis

Descriptive characteristics of the study population are presented as n (%) for categorical variables and median (interquartile range) or mean (SD) for continuous variables. Baseline differences between patients that received RIPC and those that did not were tested using chi-squared tests for categorical variables (Fisher’s Exact test for very small cells) and Wilcoxon rank-sum tests for continuous variables.

Although this analysis was based on registry data with modest sample size, there were only trivial differences in baseline characteristics between the patients that received RIPC and those that did not receive RIPC. Therefore, the conventional approach to assessing association in non-randomized studies (performing multivariable regression to “adjust” for characteristics that differ between the treatment groups) does not require that many covariates be accounted for with multivariable modeling. Nevertheless, to assess the robustness of our results when accounting for potential confounders, we present the effect of RIPC on clinical HF with a multivariable logistic regression model adjusted for variable with significant baseline difference: cardiac arrest on first medical contact. We also performed subgroup analysis excluding patients with cardiac arrest on first medical contact.

For outcomes analyses, we report i) the percentage of patients who experienced in-hospital clinical HF, and ii) the median BNP value. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). Two-sided p values <0.05 were considered as indicative of statistical significance.

2.1

Protocol implementation and data sources

Data from the National Cardiovascular Data Registry® (NCDR) Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With the Guidelines™ (ACTION Registry–GWTG) from two tertiary care STEMI receiving centers (University of Pittsburgh Medical Center Presbyterian and Passavant Hospital) in the United States that are utilizing RIPC during inter-facility helicopter transport of STEMI patients for pPCI were used for this study. The ACTION Registry–GWTG is a nationwide, voluntary, quality improvement registry sponsored by the American College of Cardiology and the American Heart Association . The conduct of the RIPC protocol during helicopter transport of STEMI patients transferred to our two receiving facilities has been previously published . In summary, RIPC was performed during inter-facility helicopter transport by repeated 5-min cycles of inflation to 200 mmHg and deflation of a blood pressure cuff in the upper arm. A maximum of four cycles of RIPC were performed en route, and standard medical care for these patients and timeliness of transport were prioritized over RIPC. The protocol was approved by the University of Pittsburgh Institutional Review Board, the Pennsylvania Department of Health, the state EMS advisory council, and the regional Emergency Medical Services (EMS) council.

2.2

Patient population

Patients with STEMI (n = 536) that presented to the two PCI centers for pPCI from March 2013 through September 2015 were identified. Analyses were limited to STEMI patients with inter-facility air transport within the period that the RIPC quality improvement protocol was implemented. The protocol was first implemented at two air medical base sites as a pilot and then extended to 12 additional base sites, resulting in a cohort of patients that did or did not receive RIPC. STEMI was defined as chest pain or epigastric pain for more than 30 min and either (a) new ST elevation at the J point in two contiguous leads with the cut-off points of ≥0.2 mV in men or ≥0.15 mV in women in leads V2-V3 or ≥0.1 mV in all other leads or (b) new or presumed new left bundle branch block on electrocardiogram. Patients were excluded if they arrived directly to the emergency department of the two PCI centers (n = 88), were transferred from the field directly to the two PCI centers (n = 177), were transported by ground ambulance (n = 49), and those with persistent hypotension at the time of air transport (n = 3) were excluded. These patients were excluded because during the period of this study RIPC was not routinely performed in this EMS system for those transferred by ground ambulance and those with hypotension at the time of transfer. Additionally, those transferred from the field were excluded because the current analysis is limited to inter-facility transfers where multiple cycles of RIPC can be performed during transfer of the patients without delaying pPCI at the receiving facility. Given that patients with reduced LVEF are more likely to develop clinical HF symptoms, those with LVEF ≥55% (n = 69) were excluded from 219 inter-facility STEMI patients. The final population (n = 150) included in this analysis were inter-facility STEMI patients that were transported by air ambulance, received coronary stenting or plain old balloon angioplasty, and with LVEF <55% after pPCI.

2.3

Study outcomes

The main study outcome measure was the occurrence of clinical HF, defined as physician report of one or more of the following: i) unusual dyspnea on exertion or dyspnea occurring in the supine position; ii) rales or jugular venous distention on physical examination; and iii) pulmonary edema on chest x-ray presumed to be due to cardiac dysfunction. The other outcome measure was the first BNP level during hospitalization. These definitions were based on predefined criteria outlined in the ACTION Registry®–GWTG™ database. For outcomes analyses, we report i) the percentage of patients who experienced in-hospital clinical HF, and ii) the median BNP value.

2.4

Data analysis

Descriptive characteristics of the study population are presented as n (%) for categorical variables and median (interquartile range) or mean (SD) for continuous variables. Baseline differences between patients that received RIPC and those that did not were tested using chi-squared tests for categorical variables (Fisher’s Exact test for very small cells) and Wilcoxon rank-sum tests for continuous variables.

Although this analysis was based on registry data with modest sample size, there were only trivial differences in baseline characteristics between the patients that received RIPC and those that did not receive RIPC. Therefore, the conventional approach to assessing association in non-randomized studies (performing multivariable regression to “adjust” for characteristics that differ between the treatment groups) does not require that many covariates be accounted for with multivariable modeling. Nevertheless, to assess the robustness of our results when accounting for potential confounders, we present the effect of RIPC on clinical HF with a multivariable logistic regression model adjusted for variable with significant baseline difference: cardiac arrest on first medical contact. We also performed subgroup analysis excluding patients with cardiac arrest on first medical contact.

For outcomes analyses, we report i) the percentage of patients who experienced in-hospital clinical HF, and ii) the median BNP value. All statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). Two-sided p values <0.05 were considered as indicative of statistical significance.