Original Contribution

Safety of Calcium-Channel Blockers During Radial Cardiac Catheterization in Patients With Acute Myocardial Infarction or Systolic Heart Failure

Barbara D. Lawson, MD;  M. Zubair Khan, MBBS;  Richard H. Cooke, MD;  J. Emilio Exaire, MD;  Luis A. Guzman, MD;  Zachary M. Gertz, MD

Barbara D. Lawson, MD;  M. Zubair Khan, MBBS;  Richard H. Cooke, MD;  J. Emilio Exaire, MD;  Luis A. Guzman, MD;  Zachary M. Gertz, MD

Abstract: Objectives. The aim of this study was to evaluate the safety of calcium-channel blockers (CCBs) during radial artery catheterization in two populations with a contraindication to their use. Background. Cardiac catheterization performed via the radial approach has become increasingly common worldwide, but adoption has been slow in the United States. One possible explanation is concern over radial artery vasospasm, which can complicate procedures. Spasmolytic drugs, typically intra-arterial CCBs, are used to prevent spasm, but their safety is not well established in high-risk populations, such as those with ST-segment elevation myocardial infarction (STEMI) or systolic heart failure (HF), in which CCB may be contraindicated. Methods. Consecutive STEMI and HF patients undergoing cardiac catheterization over a 1-year period were prospectively evaluated. All operators in our laboratory use the radial approach unless contraindicated. All patients received CCB immediately after sheath insertion. The primary outcome of interest was change in blood pressure immediately after CCB. Procedural outcomes were also evaluated. Results. A total of 184 patients were included in the study (54 with STEMI and 129 with HF). There was a significant drop in systolic blood pressure (SBP) and diastolic blood pressure (DBP) following verapamil administration (P<.001 for both), but no change in HR (P>.99). SBP decreased more than 20 mm Hg in 15.7% of patients, none of whom required initiation of vasopressors. In regression analysis, only baseline SBP correlated significantly with the change in blood pressure. Conclusions. Patients with STEMI or HF can safely tolerate intra-arterial CCB during radial catheterization.  

J INVASIVE CARDIOL 2019;31(4):107-110. (Epub 2018 December 15).

Key words: calcium-channel blockers, radial approach, STEMI, verapamil


Cardiac catheterization has evolved over the past few decades and in many centers is now performed primarily using a radial artery approach because of its superior safety.1-3 Despite quick adoption worldwide, the use of transradial access had lagged in the United States. Many countries were using the transradial approach in >50% of cases by 2011,4 whereas the United States only increased from 1.2% of procedures in 2007 to 10.9% in 2011 and to 25.2% in 2014.5,6 Radial artery catheterization is particularly infrequent in higher-risk groups, such as those presenting with ST-segment elevation myocardial infarction (STEMI), in whom femoral access is used almost twice as often.5 Radial artery vasospasm is the main cause of crossover to femoral approach, and a potential explanation for the delayed implementation of transradial catheterization. The radial artery is smaller than other vessels (ie, femoral, brachial) and is therefore more prone to vasospasm, with the incidence ranging from 4%-20%.7-10 Vasospasm is problematic because it can limit the ability to deliver equipment or manipulate catheters. In addition to technical difficulties, radial artery spasm results in patient discomfort and can prolong door-to-balloon time and/or procedure duration.

When using a transradial approach, spasmolytic drugs are typically administered through the vascular sheath immediately after accessing the artery to minimize any potential vasospasm. The most commonly used medications are nondihydropyridine calcium-channel blockers (CCBs), nitroglycerin, and nitroprusside.8,9 Due to their negative inotropic and chronotropic effects, CCBs have been generally avoided in patients with systolic heart failure (HF) or STEMI,11-13 which may partially explain the lack of adoption of radial catheterization in these subgroups. The purpose of our study was to evaluate the safety of spasmolytic drugs in populations with a contraindication or relative contraindication to their use. 

Methods

Study population. All patient data were collected prospectively, as part of an ongoing quality-improvement initiative, and individual informed consent was therefore not obtained. Permission to review the data for research purposes was granted by the Institutional Review Board at our institution. We screened all patients undergoing cardiac catheterization for systolic HF or STEMI between July 2016 and June 2017. Systolic HF was defined as an ejection fraction (EF) <35%. STEMI was defined as ≥2 mm of ST elevation in two or more contiguous leads on electrocardiogram (ECG), and only those in whom STEMI was confirmed via angiography were included. At our institution, all operators use the radial approach whenever possible, and 5 mg of verapamil via the arterial sheath is the usual spasmolytic agent. All patients who underwent coronary angiography via the radial approach and received verapamil in the spasmolytic regimen were included in the study.

Data collection. Demographic data were collected from the electronic medical records and included age, gender, race, body mass index (BMI), and comorbid disease (diabetes mellitus, hypertension, hyperlipidemia, tobacco use). Procedural specifics collected include access site, procedure duration, medications used in radial cocktail, and number of catheters used. 

All study patients had baseline heart rate (HR) and blood pressure (BP) recorded prior to sheath insertion and administration of the spasmolytic drugs. The peak hemodynamic and atrioventricular nodal effects of injectable verapamil occur within 5 minutes, and last 10-20 minutes.11 Therefore, the lowest HR and BP recorded in the 10 minutes after medication administration were recorded. To maintain consistency, the non-invasive BP measurement was used for all time points, since the first measurement was before arterial access. We chose a 20 mm Hg drop systolic blood pressure (SBP) or initiation of vasopressor support following medication administration as clinically significant. Procedure results were also recorded. 

Statistical analysis. Continuous variables are expressed as mean ± standard deviation and categorical variables are expressed as proportions. Student’s paired t-test was used to compare the change in parameters at different time points. Multivariable regression was performed to identify clinical variables associated with a decrease in SBP. All tests of significance were two-sided, and P<.05 was considered significant. Data were analyzed using SPSS version 24 (IBM). 

Results

Baseline characteristics. Over a 12-month period, there were 222 patients who underwent coronary angiography for systolic HF or STEMI. Sixty-three patients presented with STEMI, of whom 56 had transradial cardiac catheterization. One patient did not have a BP documented prior to the administration of verapamil, and 1 patient did not receive verapamil. There were 145 patients with systolic HF, of whom 130 had transradial approach. One patient did not have a BP measured within 10 minutes of verapamil administration. The study cohort consisted of 183 patients, (54 [29.5%] in the STEMI group and 129 [70.5%] in the systolic HF group). 

Patient characteristics are shown in Table 1 and procedural details are shown in Table 2. Of the 183 patients included in the study, mean age was 60.1 ± 13.4 years and 73.8% were male. Overall, 60.7% of cases were performed via right radial approach, and 88.5% of patients were given a radial cocktail of verapamil alone. A small percentage of patients received lidocaine or nitroglycerin in addition to verapamil. 

Hemodynamic response to verapamil. There was a significant drop in both SBP and diastolic blood pressure (DBP) following the administration of verapamil, both for the entire study population as well as the individual subgroups, while HR did not change significantly (Table 3 and Figure 1). There were 29 patients (15.7%) in the entire study population who experienced a decrease in SBP of 20 mm Hg or more (19 [10.3%] in the systolic HF group and 10 [5.4%] in the STEMI group). None of these patients required the initiation of vasopressors in the 10-minute period following the administration of a single dose of verapamil. In a multivariate regression analysis, only baseline SBP correlated significantly with the change in SBP following verapamil, with higher baseline pressure predicting a larger drop in SBP. The average decline in SBP for patients with a baseline SBP <120 mm Hg was 1.9 mm Hg, whereas the average decline in SBP for patients with baseline SBP ≥120 mm Hg was 10.7 mm Hg. Only 1 patient with a baseline SBP <120 mm Hg experienced a >20 mm Hg drop in SBP. 

Eight patients (6 HF and 2 STEMI) were on dobutamine and 2 patients in the STEMI group were on norepinephrine at the time of their procedure. All of these patients were able to safely tolerate the administration of verapamil. 

Procedural outcomes. Mean procedure duration was 37.7 ± 25.6 minutes, with STEMI cases taking longer (44.7 ± 22.5 minutes) than HF cases (34.8 ± 26.5 minutes;  (P<.001). Not surprisingly, there were more percutaneous coronary interventions (PCIs) required in the STEMI group (92.7%) than in the HF group (19.4%). The majority of cases were successfully performed via the initially chosen radial access. Crossover to a femoral approach was 2.2% (all in the HF group); reasons for crossover were severe vasospasm, subclavian tortuosity, inability to seat the guide catheter, and anatomic variant that precluded the catheter from reaching the aorta (1 patient each). 

Discussion

Transradial cardiac catheterization and PCI have become increasingly common over the past decade, but are still under-utilized in the United States, with only 25% of cases being performed radially as of 2014.6 This approach is consistently associated with a lower risk of vascular complications and therefore a lower risk of bleeding,5,14,15 with the reduction being more profound in higher-risk patients such as those with acute coronary syndrome.14 Bleeding is associated with increased post-PCI morbidity and mortality,16,17 which makes the radial artery approach even more appealing. As this approach evolved, there was initial concern regarding its feasibility in high-acuity situations, such as STEMI. Several studies have demonstrated the safety of transradial catheterization in the STEMI population,1-3 both in terms of decreased bleeding and vascular complications as well as decreased mortality. 

One of the biggest obstacles encountered in transradial cardiac catheterization is radial artery vasospasm, which occurs in 4%-20% of cases7-10 and can result in technical difficulties as well as patient discomfort. The crossover rate (radial to femoral) was 9.6% in the RIFLE-STEACS trial and 3.7% in the STEMI-RADIAL trial.1,2 Neither study mentioned whether spasmolytic drugs were used during radial artery catheterization, and the routine use in our lab may explain our lower crossover rate.

Administration of a vasodilator through the arterial sheath has become the standard of care to prevent vasospasm, and numerous regimens are currently in use, including nitroglycerin, nitroprusside, diltiazem, and verapamil. Vasodilators can result in hypotension, and non-dihydropyridine calcium-channel blockers have negative inotropic and chronotropic effects.11 These hemodynamic changes are more likely to be problematic in patients with congestive heart failure or in those having a STEMI. Some CCBs have been associated with increased mortality in patients with coronary artery disease (acute coronary syndromes in particular),18,19 although data are conflicting. The prescriber information provided by Pfizer even states that intravenous verapamil is contraindicated in acute myocardial infarction and severe congestive HF.11 Patients having a STEMI may have tenuous hemodynamics, hypotension, or even shock requiring vasopressor support, making the vasodilatory effect of verapamil potentially dangerous. Verapamil administration in patients with severe left ventricular dysfunction can result in decompensation, pulmonary edema, and hypotension,11,12 and has been shown to increase hospitalizations in elderly patients with congestive HF.13 The safety of these medications in HF and STEMI patients, given by intra-arterial bolus at the time of catheterization, has not been previously reported. 

At our institution, we administer 5 mg of verapamil intra-arterially (with or without other concomitant vasodilators) immediately after the sheath is inserted. Our study demonstrates the safety of this regimen in patients presenting with HF or STEMI. Following intra-arterial verapamil, there was no significant change in HR, but a significant decrease in SBP and DBP. These hemodynamic changes were not clinically significant, however, as no patient required vasopressor support in the 10 minutes following vasodilator administration. Additionally, the majority of cases (97.8%) were able to be successfully completed via the radial approach in this population.

Study limitations. Our study has several limitations. Foremost is the small sample size, particularly in the STEMI group. This, combined with the single-institution experience, might limit the generalizability of the study results. In addition, not all patients received the same vasodilator cocktail, and we did not have sufficient data to compare outcomes based on different regimens. 

Conclusion

Patients with STEMI or HF can safely tolerate an intra-arterial bolus of spasmolytic drugs during radial catheterization, minimizing the likelihood of crossover to femoral access. Our findings should encourage operators to adopt a radial-first strategy if they are not already doing so.

References

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15.    Jolly SS, Amlani S, Hamon M, et al. Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-alanysis of randomized trials. Am Heart J. 2009;157:132-140.

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From the Division of Cardiology, Virginia Commonwealth University Pauley Heart Center, Richmond, Virginia.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 26, 2018 and accepted October 10, 2018.

Address for correspondence: Barbara D. Lawson, MD, 1200 East Broad Street, P.O. Box 980036, Richmond, VA 23298-0036. Email: barbara.lawson@vcuhealth.org

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