Faculty Spotlight: Yousif Ahmad, MD, PhD

 

Finding a Path Through (or Around) Obstacles

“While much of what we do in interventional cardiology is extraordinarily complex, it’s up to us to have the skills to treat things that are difficult,” said Yousif Ahmad, MD, PhD. “But rather than focusing on complexity, patients are much more interested in feeling better, and what risks are involved with a procedure – not whether it may give me more gray hairs. Focusing on the level of risk rather than complexity is a much more patient-focused concept.”

Dr. Ahmad, an interventional cardiologist who recently joined the UCSF faculty, brings extraordinary skill to his care of patients in the Cardiac Catheterization Lab. He also conducts research to better understand which treatments are best suited to which patients, based on meta-analyses of many different trials.

Born in Virginia to parents who originally hail from Iraq, Dr. Ahmad soon moved with his family to the United Kingdom. He grew up in Essex County in a small village a couple hours outside of London. Although his father is a physician, Dr. Ahmad initially was drawn to the humanities. However, a premed introductory course in high school convinced him to pursue medicine. He earned his bachelor’s degree in medical science and his medical degree from the University of Nottingham in England. He then completed fellowships in cardiology and interventional cardiology, as well as a PhD in aortic and coronary physiology, at Imperial College London.

To further build his skills, Dr. Ahmad completed additional fellowships in complex and high-risk percutaneous coronary intervention and mechanical circulatory support from Columbia University Medical Center in New York, and in structural heart disease from Cedars-Sinai Medical Center in Los Angeles.

“I liked that cardiology has more randomized trials than probably any field of medicine, so you can have a good degree of certainty that you’re doing the right things for your patients because there’s a high level of evidence supporting everything we do,” said Dr. Ahmad. “It’s also gratifying that patients often improve quickly, whether it’s their response to medication or procedures in interventional cardiology.”

Within cardiology, Dr. Ahmad was immediately drawn to interventional cardiology – a subspecialty of cardiology that treats problems of the heart and blood vessels by using catheters to perform angioplasties, place stents, replace heart valves, and conduct other minimally invasive procedures. “Some of the first rotations I did as a medical trainee were in the cath lab, and it was very intuitive,” he said. “I could understand the goals of treatment and how to assess the results.”

Putting Hypotheses to the Test

One of his key research mentors at Imperial College London was Darrel Francis, MD. “He taught me how to evaluate studies, the importance of randomization and blinding, and other core concepts of clinical research,” said Dr. Ahmad. “Although he grilled me very hard in my initial interview, he has an incredible sense of humor and is very likeable. It was also a very exciting time to be at Imperial, because there was a huge amount of clinical research and innovation going on.”

One of those initiatives was the Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial, led by Dr. Francis and Rasha Al-Lamee, MBBS, PhD, another one of Dr. Ahmad’s mentors. “Part of their philosophy is not to accept conventional wisdom or expert consensus on anything,” said Dr. Ahmad. “Instead, we need to subject all our beliefs to rigorous testing, which oftentimes means randomizing patients – and if it’s for symptom benefit, doing this in a blinded way as well.”

ORBITA was designed to test the efficacy of stenting in alleviating the symptoms of angina, a type of chest pain caused by reduced blood flow to the heart. “All the drugs people take for angina have been assessed in placebo-controlled trials, but stenting had not been tested in this same rigorous, placebo-controlled way,” said Dr. Ahmad, who was part of the ORBITA team.

In this trial, all patients first underwent six weeks of medication optimization, getting on ideal dosages of the best antianginal medications. Then they participated in baseline testing to measure their exercise capacity. Patients then were randomized to either receive a stent or undergo a placebo procedure, but did not find out which they received until the end of the trial. After six more weeks, researchers tested their exercise capacity again. Although the stent group had improved exercise time compared with baseline testing, researchers found that there was no statistically significant difference between the two groups.

“ORBITA taught me that you can test procedures in a blinded way, and how important it is to design a study to test your hypothesis,” said Dr. Ahmad. “You can now very reasonably give options to patients with stable angina, letting them choose between starting two to three medications over the coming weeks, or undergoing a stent procedure. A lot of it depends on the patient’s preferences, which allows us to tailor care to each patient.”

The ORBITA findings initially caused an uproar, in part because critics said that it suggested that stenting no more effective than a placebo procedure. To answer those questions, Dr. Al-Lamee and her team conducted a follow-up trial, ORBITA-2, in which all patients were taken off antianginal medications in order to isolate the effects of stenting versus placebo in the absence of medication. That trial demonstrated a clear benefit to the stent group in the absence of any antianginal drugs. Although Dr. Ahmad was not involved with ORBITA-2, its results help to guide his clinical practice.

A central factor in that decision-making process is an individual patient’s risk. “If it’s a straightforward stent procedure, it’s reasonable to offer that if a patient would much rather reduce their medication burden,” said Dr. Ahmad. “On the other hand, if it’s a high-risk procedure, I would reserve it for patients who are refractory after medication. Risk is something I think about a lot, and it’s at the center of many of my conversations with patients.”

One important caveat is that the ORBITA trial focused on patients with stable coronary artery disease: those with only one coronary artery affected, who had not had a recent heart attack, and who only developed chest pain when exercising – not while at rest. “Unstable patients, including those with acute coronary syndrome, those who have recently had a heart attack and have more than one blockage, or those who have chest pain at rest, have a clear benefit for stenting,” said Dr. Ahmad. “There have already been many randomized trials of unstable coronary disease. When you meta-analyze them, you can see clear benefits in reducing heart attacks and death by stenting or invasive treatment versus medical treatment alone.”

The Democratization of Innovation

While earning his PhD at Imperial College London, Dr. Ahmad led research on patients who had both coronary disease – narrowing of the blood vessels that supply the heart with oxygen – as well as aortic stenosis, in which one of the valves in the heart becomes narrowed, impeding normal blood flow from the heart to the rest of the body. “It can be hard to know the relative contribution of each of these problems to a patient’s overall condition, since they often coexist and produce similar symptoms, including chest pain and shortness of breath,” said Dr. Ahmad.

For his dissertation, he thoroughly measured coronary pressure and flow – also known as coronary physiology – in patients with both coronary disease and aortic stenosis. Then he and his colleagues performed transcatheter aortic valve replacement (TAVR), and immediately reassessed coronary circulation in the absence of aortic stenosis. “In this way, each patient serves as their own control, because nothing changed about them other than their aortic valve being replaced,” said Dr. Ahmad. “That allowed us to really isolate the impact of the valve on their coronary circulation.”

One of their key learnings was that medications intended to augment blood flow (such as those used to measure FFR) are less effective if the patient has aortic stenosis. They also found that treating the aortic stenosis provided the biggest hemodynamic benefit overall, unless the patient’s coronary stenosis was very severe.

To engage in this research, Dr. Ahmad utilized a relatively new method of measuring coronary pressure which was developed by other mentors at Imperial, Justin Davies, MD, PhD, and Sayan Sen, MD, PhD. Traditionally, clinicians have used something called fractional flow reserve (FFR) to assess severity of coronary artery stenosis, which measures pressure in the coronary artery in the area both upstream and downstream of a blockage. However, FFR requires administering medicine to increase blood flow, and these drugs are costly, time-consuming to administer, and sometimes have side effects. Unfortunately, that decreased the use of FFR in real-world clinical settings, even though studies suggest it is very beneficial for patients undergoing stenting.

Through a partnership between cardiologists and bioengineers, Dr. Ahmad’s mentors found a better way to obtain these measurements without medication. They developed a method called instantaneous wave-free ratio (iFR), taking advantage of the few milliseconds each cardiac cycle when resistance to blood flow is already naturally low. By timing their measurements to this narrow window during diastole, they eliminated the need to administer drugs to obtain these pressure measurements. 

“It was a very elegant way to circumvent all the problems associated with the drugs needed for FFR, which led to increased adoption of coronary physiology measurements and better patient outcomes,” said Dr. Ahmad. “It was amazing how quickly my mentors took iFR from concept, to testing it head-to-head with FFR in large trials with real patients, and then into the guidelines. It’s now routinely used in cath labs around the world.”

That was an inspiring model for how to magnify the impact of discovery. “The democratization of innovation is very important,” said Dr. Ahmad. “It’s not very useful if only the world’s experts can use it. The only way developments scale and have a broader impact is if it’s easy for others to use.” 

‘Many Ways to Solve a Case’

After finishing his PhD and fellowships in general cardiology and interventional cardiology, Dr. Ahmad came to the U.S. for advanced procedural training in 2019. He spent a year at Columbia University, developing skills for performing complex and high-risk percutaneous coronary interventions (PCIs) under the direction of Dimitrios Karmpaliotis, MD, PhD. “He taught me the fastidious approach to doing procedures, never accepting that something might be ‘good enough,’” said Dr. Ahmad. “You have to make it as good as it can be, and it doesn’t matter if that takes a very long time and is difficult. His voice is still in my head when I do procedures.”

He also worked closely with Jeffrey Moses, MD. “He was immensely talented at doing procedures, but has also had a very impressive academic career running studies and pioneering many therapies that have impacted millions of patients,” said Dr. Ahmad. “He’s one of the giants of our field, and the way he combines clinical research with doing procedures to a high level is something I really aspire to.”

During that year, Dr. Ahmad developed expertise in treating chronic total occlusions (CTOs). “That means the coronary artery is 100 percent closed, and it has happened gradually over time,” said Dr. Ahmad. “If it becomes completely occluded acutely, that’s a heart attack – something very dramatic that needs immediate treatment with stenting. Most of the time, acute occlusions are caused by a thrombus (blood clot) which is soft, and often the plaque that underlies the thrombus is also soft, so that’s easy to treat. Although it can be challenging to manage how sick a patient with a heart attack is, the technical aspect [of stenting] is generally not challenging whatsoever.”

However, treating a CTO is completely different. “When an occlusion happens chronically, the manifestation is often not as dramatic, but when the artery is 100 percent closed and it’s chronic, it's very hard to open,” said Dr. Ahmad. “It’s technically the most demanding thing we do in the cath lab, and you need very specific procedural expertise and different equipment.”

That’s partly because the “total” nature of the blockage makes it difficult to trace the path of the artery. “Just going from 99 percent to 100 percent blockage changes the calculus completely,” said Dr. Ahmad. “Even when an artery is 99 percent closed, chronically, there’s still blood flow in the forward direction, and we can see where we need to go. Oftentimes the challenge with a CTO is there’s a lot of what we call ‘ambiguity,’ because you can’t see where to go. Even if we inject contrast into an artery, that contrast can no longer travel and we can’t see the artery.”

CTOs are also challenging to treat because they usually involve calcified arteries which have hardened over time. This makes it extremely difficult to pass a wire or other catheter-based equipment through an obstruction in the blood vessel. Unlike an acute occlusion, which is soft like butter, a chronic occlusion is hard like rock.

Sometimes Dr. Ahmad and his colleagues perform a dissection. This involves gently poking a wire into the wall of the blood vessel to get around the blockage, then re-entering the blood vessel downstream of the blockage – a bit like driving on the shoulder of a highway when traffic is at a complete standstill. “It’s technically demanding but can be a very good option, and we’ve treated many UCSF patients this way with a lot of success,” he said. 

Other times, they access the blockage through a retrograde approach. This involves going downstream of the blockage via collateral vessels, which are “backroads” that the body develops in response to blockages in the main vessel. The collaterals keep the heart muscle alive, but provide significantly less blood flow than the coronary arteries. “In a lot of cases, you flip between antegrade and retrograde [approaches] during the case to get it done,” said Dr. Ahmad.

He and his colleagues have many other advanced techniques for tackling these difficult situations. “I like [CTO] procedures, because you’re always trying to plot out the safest way to get a successful result,” said Dr. Ahmad. “There are many ways to solve a case, and I enjoy the cognitive challenge.”

After his fellowship at Columbia, Dr. Ahmad spent another year completing a structural heart disease and advanced coronary fellowship at Cedars-Sinai Medical Center in Los Angeles, continuing to perform a high volume of CTO cases alongside TAVR and other valve procedures. He then joined the faculty at Yale University, eventually becoming the director of the complex and high-risk PCI program and greatly increasing the number and types of those cases performed there. He also enrolled many patients in clinical trials of the latest innovations in interventional cardiology.

Dr. Ahmad also served as associate director of the interventional cardiology fellowship program. “Probably the thing I enjoyed most from my three years at Yale was seeing fellows I had trained go into practice,” he said. “They would ask me for advice on cases, but after a year or two, they would show me cases they had done and say, ‘All the things you taught me allowed me to treat this patient.’”

Piecing Together the Big Picture

In addition to his heavy clinical caseload, Dr. Ahmad leads many research endeavors. In particular, he specializes in conducting meta-analyses. These studies of multiple clinical trials are akin to piecing together a jigsaw puzzle, where every piece contains important information, but the collective picture tells a story that no single puzzle piece could convey.

“We run [individual] trials as best we can, but we get the highest level of evidence when we synthesize multiple trials together, because you can look for consistencies so you know that one trial is not an outlier,” said Dr. Ahmad. “You also dramatically increase your statistical power. For example, there may be smaller benefits that may not emerge in one trial of 2,000 patients, but you might see it if you synthesize multiple trials.”

“Medicine is an art,” he continued. “Patients aren’t exactly represented by trials, but they’re normally fairly well represented, and our job as their doctors is to understand as best as possible which category best fits each patient. If you look at a meta-analysis which includes 10 trials that all enroll slightly different populations, if you see a consistent effect across all of them, you can be reassured that your patient is likely well-represented by the available data.”

One of his meta-analyses investigated whether patients who have had a heart attack do better if they receive a stent just for their “culprit” lesion – the blockage that caused the heart attack – or if all remaining blockages should also be stented instead of treated with medication, a process called complete revascularization. “Stenting of the culprit lesion has already been established as standard of care by randomized trials, but it was unknown what to do with the other blockages,” said Dr. Ahmad. “There have now been a number of randomized trials that compared culprit-only to complete revascularization.”

He and his colleagues performed a meta-analysis of these trials, showing for the first time that complete revascularization demonstrated a benefit in all-cause mortality, and reconfirmed benefits in reducing heart attack and cardiovascular death. They also did not identify any concerning safety issues – such as thrombosis, bleeding, or kidney function – with complete revascularization. “Our analysis showed beyond any doubt that complete revascularization should be the optimal choice for patients with multivessel disease after a heart attack,” said Dr. Ahmad. However, the ideal timing of that complete revascularization – either immediately after a heart attack, or in a more staged manner – still requires further study.

Dr. Ahmad also used meta-analysis to study outcomes for patients with left main coronary artery disease, one of the most serious forms of coronary disease, comparing outcomes between patients who received left main stenting versus bypass surgery. They found that there was no difference in survival at either five or 10 years between the two procedures, though there were other nuances that might influence treatment decisions.

“For example, I had a patient recently with significant left main disease, but without other significant coronary disease in other vessels and without diabetes,” said Dr. Ahmad. “We discussed his case at our conference with surgeons and other interventional cardiologists, and we all felt there was equipoise between the two approaches based on the studies of his anatomy, and it was really up to the patient.”

“I told him if he had bypass there was a lower risk of needing procedures in the future and a lower risk of future heart attack, because the bypass can protect all the artery, but he’d have to go through a big surgery and the recovery,” said Dr. Ahmad. “My colleague, cardiac surgeon Dr. Amy Fiedler, also shared the same information with him. The patient opted for stenting, and we all felt that was a good decision. It’s nice to have the data to counsel patients appropriately so they can make an informed decision.”

Dr. Ahmad also has conducted meta-analyses of intravascular imaging, which allows interventional cardiologists to acquire images from within a diseased blood vessel. “When you put the catheter inside the artery, you can measure very precisely how large the artery is and therefore what size the stent needs to be,” he said. “You can also see how much calcium there is and what treatment you need to use to modify it. After placing a stent, you can check that it’s perfectly positioned and expanded. An imaging catheter allows us to see things that just are not visible with an angiogram, which is just a 2D X-ray from outside the body.”

Their recent meta-analysis in the Lancet showed a 25 percent reduction in all-cause death if a stent procedure is guided by intravascular imaging versus just angiogram. Another of their studies showed similar benefits, supporting use of intravascular imaging as standard of care. “The benefits are undeniable, but usage remains very low in the community,” said Dr. Ahmad. “The imaging catheter itself is not magic – you have to understand what you’re looking at, interpret it, and apply it, then check again with imaging to ensure you have an optimal result. We have to educate people about how to do this, and our fellows at UCSF get very good experience with intravascular imaging.” 

One of Dr. Ahmad’s dream research projects would be to repeat historical trials that form the evidence base about the relative benefits of stenting compared with medical therapy or bypass surgery. “Many of those trials were done without intravascular imaging, and I strongly believe the results would be significantly different if they used it,” said Dr. Ahmad.

When advising trainees about how to conduct a robust meta-analysis, he encourages them to start with a good question they want to answer, then making sure they pool high-quality trials. “If you put in a lot of low-quality data, you just get a synthesis of low-quality data – you don’t enhance the data quality by pooling it,” he said. “For example, observational studies have a very limited ability to tell us about how effective different therapies are. Nearly all of the meta-analyses I conduct use randomized trials only.”

He notes that meta-analysis is sometimes maligned, partly because it is not always done properly. “In the current era, there are a lot of software packages in which you can just type in some numbers, and you get very attractive figures made for you,” said Dr. Ahmad. “The problem is when people do this without understanding the statistics or science behind it. The other trap people fall into is inappropriately pooling trials that look at dramatically different patient populations. For example, it would not be appropriate to do a meta-analysis combining stenting for ST-elevation myocardial infarction and stenting for stable coronary disease.”

Blending Insight, Skill and Compassion

Although Dr. Ahmad greatly enjoyed his work at Yale, the opportunity to join the UCSF Division of Cardiology was too good to pass up. “The UCSF Interventional Cardiology program is undergoing a renaissance in the last couple of years since Sammy Elmariah has joined [as chief of interventional cardiology] and new faculty have been recruited,” he said. “I was excited to be part of that.”

“Dr. Ahmad has been a tremendous addition to the UCSF Interventional Cardiology program,” said Dr. Elmariah. “He has significantly enhanced our program’s expertise in treating patients with complex coronary artery disease, including those with chronic total occlusions, and those with aortic valve disease. Dr. Ahmad blends profound clinical insight, advanced technical skill, and heartfelt compassion to deliver personalized care to his patients.”

“We’re very excited about the wealth of training, experience and research that Yousif brings to UCSF,” said Krishan Soni, MD, MBA, director of the Interventional Coronary Artery Disease Program. “He has deep expertise in treating advanced coronary and structural disease, honed through his advanced fellowships at Columbia and Cedars-Sinai, which allows UCSF to treat some of the most technically complex patients. He also has a very clear and analytical manner at the bedside, so trainees gain excellent skills in learning how to manage complex coronary and valve conditions. Yousif also brings a very strong research background, both as a principal investigator in many trials as well as leading impactful meta-analyses, which will bolster our interventional cardiology research enterprise.”

Dr. Ahmad appreciates the collaborative environment at UCSF, as well as the camaraderie with other faculty members. “Krishan Soni has been an amazing partner to me since I joined UCSF,” said Dr. Ahmad. “We do our chronic total occlusion cases together, which really helps safety and efficiency. Our patients get two attending interventional cardiologists treating them. I also often do high-risk TAVRs with Sammy or Michela Faggioni. I also enjoy our partnership with cardiac surgery. We have a lot of joint conferences, and we see patients together, consult with one another, and come up with a plan. Everyone has a common goal and wants to work together. I’ve been at a lot of different institutions, and not everywhere has an outstanding culture like that. There’s no ego: we all want to elevate one another’s programs, and patients benefit the most.”

He looks forward to working together to build the program. “I hope we continue to increase our volume, including for high-risk, complex cases,” said Dr. Ahmad. “I’d like us to be a flagship site for clinical trials, to perform well in research, and provide our patients access to therapies that are not yet commercially available anywhere in the U.S. For example, we now have the coronary sinus reducer – a novel treatment for patients with angina – and we will soon have new devices for left ventricular support, new valves, and novel devices to modify calcium.”

Education is also a priority. “I want to continue training high-quality fellows, and to become a training destination for fellows from all over the country,” said Dr. Ahmad. “Our interventional fellows get an amazing breadth and depth of experience in high-risk procedures…. Ultimately, I hope this becomes one of the top interventional programs in the country.”

Dr. Ahmad’s dedication to patient care is at the heart all he does. “Interventional cardiology techniques have improved dramatically in the last decade or so, both for valvular heart disease and coronary disease,” he said. “In expert programs, particularly when people have dedicated training fellowships to learn these techniques, there’s almost nothing we can’t do interventionally, without surgery. Many patients should have surgery, but if they are not a surgical candidate or aren’t willing to undergo surgery, I would encourage people to seek a second opinion. At UCSF, we’ve had a lot of success treating very high-risk patients over the last year with non-surgical approaches, with really good outcomes.”

“A large part of my practice is patients who have been told that they have no options,” continued Dr. Ahmad. “Those are the patients I enjoy helping the most, because they’ve often been struggling for a very long time. When they eventually find their way to the right place, it’s very gratifying to help them.”

Outside of medicine, Dr. Ahmad enjoys spending time with his wife, Nicole, and their two young children, Zahra and Rami. He is also an avid fan of the Warriors, the 49ers, and Aston Villa, an English Premier League football team.

-     Elizabeth Chur