Please remind us of when and why you started performing transradial procedures.

I became interested in radial intervention in early 2008, when I saw a study investigating sex differences in bleeding and vascular complications using the femoral versus radial approach. My research focuses on sex differences in cardiovascular disease, and the biggest sex difference we see in the cath lab is in bleeding and vascular complications, as women have two to three times the risk compared with men when the femoral approach is used. I had been involved in research demonstrating that being a woman, particularly a small woman, is an independent predictor for retroperitoneal bleeding, and in fact, 75% of the retroperitoneal bleeds occur in women.

At this time, there was no training available on the West Coast, so I flew to New York for training. I brought the approach back to Stanford and have turned our institution into a West Coast training site. I also travel to hospitals, primarily on the West Coast, to get them up and running. It's been a fantastic and rewarding experience. Even more significant to me is watching my fellows learn the procedure. They leave Stanford with stellar access skills and can then provide the best care for each individual patient.

Since you wrote for us in 2011, has progress been made in engineering/manufacturing transradial-specific devices? What would be highest atop your wish list?

In the United States, there has been an increasing interest among device companies to produce radial guides, and hopefully, we'll see more availability of smaller (5 F) guides in the near future. The past year has provided important data regarding methods of reducing radial artery occlusion to < 1%, and this has led to methods that we consider part of a “best practice” for radial procedures. Most importantly is achieving patent hemostasis with a radial compression device. Also important are adequate heparin dosing and minimizing sheath/catheter diameters. The increased availability of good 5-F guides designed for the radial approach will help us with this latter goal, but the challenge will be to develop these guides in such a way that they offer a spacious internal diameter, as well as adequate support and backup. Along these same lines, and at the top of my wish list, is the availability of a sheathless guide in the United States. Although this will be a niche guide that is only used in particular situations, it will be nice to have when you need it. We can do sheathless in the United States now by piecing together a transition with a coronary balloon or a “mother-daughter” system, but I would like to have a dedicated sheathless guide.

Overall, what would you say is the biggest advantage of transradial access? The biggest disadvantage?

Although the most important advantage is a reduction in bleeding and vascular complications, the biggest advantage is patient satisfaction. Patients find it so much more comfortable and convenient than a femoral approach that they will literally get on a plane and fly to you in order to have their procedure done radially. I actually believe that patient request and preference has become a bigger driver than bleeding/vascular complications in getting operators to change from femoral to radial. In some towns, there are two hospitals, and whoever is doing radial is going to have the upper hand (no pun intended) in getting referrals.

I don't think there are any true disadvantages to the radial approach, but there are some challenges. The first challenge is getting oneself trained. The good news is that training is increasingly becoming available, and there are a number of operators who, like me, are doing one-on-one training either at their own institution or at the trainee's institution. The advantage of the latter is that we can not only train the physician on the technique, but we can improve upon the entire system, from preprocedural protocols to setting up the table to postprocedure care by also working with the nurses and technicians.

When you participate in device evaluation trials, do you always investigate patient sex differences?

Yes, when I participate in a device evaluation trial, my role is often asking about sex differences. We have done some research on sex differences with drug-eluting stents and fractional flow reserve, and I am looking forward to doing the same with left ventricular assist devices and renal denervation. It's important for us to know if our devices are equally safe and efficacious in women and men, and if not, to act accordingly.

What have you learned thus far in your studies on sex differences in terms of coronary pathophysiology?

The research for my NHLBI Mentored Patient- Oriented Research Career Development Award (K23) has been to study differences in coronary pathophysiology between women and men who have anginal symptoms but normal-appearing coronary arteries on angiography. As you may know, this is a common, but poorly understood group of patients. More than 20% of patients presenting to the cath lab with symptoms concerning for ischemia are found to have normal coronary arteries. We typically tell these patients that they're fine and that their symptoms are not from their heart. However, commonly, their symptoms continue, and they get multiple referrals and tests with no identified etiology. We know from the WISE study that a significant number of these patients (> 50%) actually do have a coronary abnormality as a cause of their chest pain, namely endothelial dysfunction and/or microvascular disease. My research extends WISE to also include similarly presenting men and asks the question of whether or not these vascular function abnormalities are more common in one sex versus the other.

Although I am just now completing enrollment, there has been one other study suggesting that diffuse endothelial dysfunction is more common in men, whereas microvascular disease is more common in women. In investigating these patients, we have also identified a large number of myocardial bridges, which raises new and intriguing questions to study. Ultimately, I would like to see more interventionists performing vascular function testing, as it has the potential to benefit a large number of patients.

What have you observed so far in your research on symptomatic myocardial bridges using Doppler and pressure measurements, as well as IVUS? What symptoms alert you that this anatomical anomaly might be present?

Although myocardial bridges are quite common, occurring in approximately 30% of the general population, and typically very benign, we know that there is a small subset of the population that has significant symptoms caused by a myocardial bridge, and in rare cases, these bridges have been associated with myocardial infarction and sudden cardiac death. I have an imaging colleague who has found a novel method of identifying patients with myocardial bridging using stress echocardiography. For those patients who are significantly symptomatic, we have been taking them to the cath lab, where we initially confirm the presence and characteristics of the bridge using IVUS. It is well known that angiography alone is very poor at identifying myocardial bridging. Once we have identified the bridge, we use a Doppler flow wire to investigate the changes in pressure and flow distal to, within, and proximal to the bridge during rest and stress (using intravenous dobutamine).

These patients present with symptoms that are usually very similar to typical angina. They have chest pain with or without shortness of breath with physical exertion, and it often begins once they achieve a certain heart rate. They may also have a lot of premature ventricular contractions, or even runs of ventricular tachycardia, which we think is secondary to ischemia. When we identify patients with a hemodynamically significant bridge, we initially try medical therapy with beta-blockers as first-line treatment, and calcium-channel blockers as second-line treatment. If medical therapy fails, and the patient's quality of life has become intolerable, we have sent a handful of patients for surgical unroofing with, overall, very positive results.

In what ways has Stanford reached out to the community to provide women with cardiovascular education?

Beyond research and clinical care, Women's Heart Health at Stanford provides ongoing education to the lay community, as well as to physicians. Awareness of sex differences is, unfortunately, lacking in both groups. Most of our education is provided through lectures or symposia, which are given at Stanford, large businesses, community functions, and our local cardiac rehab center. We have also done YouTube videos, radio and TV broadcasts, and have even been on the Jumbotron on Highway 101—anything to get the word out.

I have a great team who helps cover cardiovascular care surrounding interventional cardiology, including primary and secondary prevention, as well as other cardiovascular issues such as electrophysiology and valvular heart disease. This allows us to have a positive impact on as many women as possible. I will also add that it has become quite clear to me that our work also benefits men. When you study sex differences, you aren't just studying women, you're studying women and men, and figuring out when they can be treated the same and when they may need to be treated differently. My ultimate hope is that we will help improve the cardiovascular care and outcomes of all of our patients.

Jennifer A. Tremmel, MD, MS, is Assistant Professor of Medicine (Cardiovascular) and Clinical Director of the Women's Heart Health Program at Stanford University Medical Center in Stanford, California. She has disclosed that she has no financial interests related to this article. Dr. Tremmel may be reached at jtremmel@stanford.edu.