Beyond Weight Loss, Heart Health Improves after Bariatric Surgery

Tammy L. Kindel, MD, PhD, FACS, FASMBS, recipient of the 2020–2025 George H. A. Clowes Jr., MD, FACS, Memorial Research Career Development Award—which is supported through contributions to the ACS Foundation with funding from The Clowes Fund, Inc.—recalls treating a patient in his mid-30s with severe obesity, high blood pressure, and obstructive sleep apnea who had developed heart failure.

The patient was using continuous positive airway pressure therapy for obstructive sleep apnea and, despite taking multiple medications for his heart failure, did not recover normal cardiac function and was listed for a heart transplant. However, he was hesitant to undergo bariatric surgery—even though the procedure could mean he no longer required a heart transplant.

“There really was no further medical treatment that was going to give him a chance to improve his heart function,” explained Dr. Kindel, director of the Bariatric Surgery Program at Froedtert Hospital and the Medical College of Wisconsin (MCW) in Milwaukee. “Studies suggest that there is a 50% chance of meaningful cardiac recovery after bariatric surgery.”

After several conversations explaining the potential risks and benefits of surgery, particularly related to his cardiac function, the patient eventually had bariatric surgery. A year after surgery, the patient is on significantly less medication, he’s taking walks with his kids, and he is no longer listed for a heart transplant.

Dr. Kindel received the Clowes Award, which supports the work of a promising young surgical investigator, for her research project, “The Role of GLP-1 in Cardiac Recovery after Bariatric Surgery in Obesity-Induced Heart Failure.” The award consists of a stipend of $45,000 for each of 5 years and is open to an ACS Fellow or Associate Fellow who has completed an accredited residency in general surgery, vascular integrated surgery, cardiothoracic integrated surgery, or plastic surgery.

Clowes Award and Rebuilding a Rodent Colony

Dr. Kindel was presented with the Clowes Award at the height of the COVID-19 pandemic, which turned out to be fortuitous.

“At our institution, like so many basic science laboratories during the COVID shutdown, we were not permitted to continue active research studies,” explained Dr. Kindel. “We had developed a very unique rat colony at MCW partnering with the rat genome core that is not available anywhere else in the country. This grant allowed me to start over and rebuild this rat genome experiment to study how loss of a specific cellular receptor affects cardiac function after bariatric surgery. We used 2 years of the Clowes funding to reinvigorate the laboratory and rebuild our animal colony. Without that funding, this exciting and important project could not have continued.”

Using animal models of obesity and metabolic disease, Dr. Kindel’s research endeavors to go beyond bariatric surgery and weight loss, which has been proven to enhance cardiovascular health, to examine the role of surgery in changing gut hormones, bile acids, and microbiome signaling that are linked to improved heart health.

Protected Time for Research

Dr. Kindel’s preliminary research was supported by the Clowes Award, a KL2 (an award housed within the Medical College of Wisconsin) and a K08 award, the latter two of which were funded by the National Institutes of Health (NIH). The aim of all three awards is to support career development for early career researchers in the form of staffing, supplies, salary, and protected research time.

“These awards are designed to help clinician-scientists, in my case, surgeon-scientists, have dedicated time that is protected away from our clinical duties,” said Dr. Kindel. “This funding, from sources such as the Clowes Award, provides the opportunity to expand the scope of our work faster, accelerate research results quicker, and offer additional salary support for research staff. I need a strong research team present every day in the wet laboratory to continue research studies while I’m in bariatric clinic or the operating room. This type of research requires a dedicated team effort to move the science forward.”

Dr. Kindel’s preliminary research data, supported in part by the Clowes Award, led to a $2.2 million R01 award funded by the NIH/National Heart, Lung, and Blood Institute to expand her cardiac studies.

“Without the Clowes financial support, it is unclear whether I would have been able to transition my K08 to my R01 project, especially given the COVID-19 pandemic and delay in research across the country,” she said. “Documenting to the NIH that the American College of Surgeons believed in our research project line and was willing to continue to fund our work provided a strong track record of success and reliability as a principal investigator. Funding has a way to beget more funding.”

Dr. Kindel received the 5-year R01 grant (2022–2027) for the project titled, “Identifying Gut Microbiome Mediated Mechanisms for Diastolic Dysfunction Improvement after Bariatric Surgery.”¹ Heart failure with preserved ejection fraction is closely associated with obesity, with no treatment known to decrease cardiovascular mortality.

Her project focuses on understanding how bariatric surgery improves heart function in patients with obesity-related heart failure and will lead to the development of new surgical and nonsurgical therapies for this disease.

A primary goal of Dr. Kindel’s current research, which is supported by the R01 grant, is to collect biospecimens from patients with heart failure with preserved ejection fraction before and after sleeve gastrectomy in an effort to verify that the mechanisms involved in the animal models correctly translate to human patients, which in turn, supports the use of metabolic surgery as treatment for obesity-associated heart failure.² “We believe that sleeve gastrectomy causes unique changes to both the enterohepatic circulation of bile acids as well as gut microbiome which beneficially helps patients with obesity-associated heart failure.”

Far-Reaching Implications

Dr. Kindel’s research has examined other facets of how the microbiome is tethered to heart health—specifically how certain antibiotics administered at the time of bariatric surgery can alter the gut flora, resulting in an improved resolution rate of hypertension for patients.

“We’ve determined that the gut microbiome is driving some of the improvements in blood pressure after bariatric surgery that is independent of weight loss,” explained Dr. Kindel, who started her work in this area with rats and mice because it is possible to carefully control diet, calorie intake, activity, and metabolic disease in rodent models. These animal models revealed improved hypertension control with surgery versus calorie-restrictive diets. With work supported by the Clowes Award, they then were able to show in an animal model a direct causation between the changes in blood pressure after surgery and the gut microbiome.

To translate these animal findings to humans, Dr. Kindel conducted a retrospective analysis of adult bariatric patients who underwent surgery between 2012 and 2016. The results indicated that a single dose of prophylactic perioperative, intravenous clindamycin was associated with significantly increased resolution of postoperative hypertension. This was followed by a randomized controlled trial of one antibiotic versus another at the time of Roux-en-Y gastric bypass.³

“We found that a single antibiotic given at the same type of bariatric surgery is affecting how the gut microbiome beneficially repopulates long term to improve blood pressure,” she said. “We’re very excited about the mechanisms as it gives us some potential therapeutic targets to magnify at the time of surgery to improve cardiovascular outcomes for our patients.”

Dr. Kindel noted that the broader application of these findings is that many decisions made by clinicians at the time of gastrointestinal surgery—such as administering antibiotics and other pharmaceuticals—can affect gut microflora, and in turn, cause unanticipated negative or positive patient outcomes. “We tend to not think about all of the short-term medications we use at the time of surgery (such as antacids, antibiotics, pain medications, anti-emetics) that can have substantial long-lasting effects on how that surgery works. However, gastrointestinal surgery and specifically bariatric surgery is unique, in that on the one day of surgery, we are potentially repopulating the gut microbiome for the long term due to the new anatomy. This can impact multiple different systems including immune function, metabolic disease, and cardiovascular health, to name a few.”

Challenges of Being a “Triple Threat” Surgeon

As is the case for many surgeon-scientists, Dr. Kindel’s work at the patient’s bedside informs her role as a researcher. “The clinician-scientist asks the most relevant questions because we’re taking care of the patients every day. It’s been very rewarding to take some of the problems or questions that we have, such as ‘Why is one person’s diabetes getting better and another person’s not? or ‘Why does it seem that one surgery works better than another?,’ study them systematically in the lab, and then translate those findings back to the patients. It’s a very full circle moment as a surgeon and scientist.”

Unfortunately, the struggle for the surgeon-scientist to succeed as a “triple threat” surgeon who can operate, teach, and conduct research is often tied to challenges in obtaining funding.⁴

“Surgeon-scientists are historically viewed differently than other clinician-scientists because it is well known that part of our time is spent in the operating room,” said Dr. Kindel. “As surgeons, we have unpredictable days despite our best efforts where a patient emergency requires us to be at the bedside or in the operating room and not in the laboratory. Having funding mechanisms like what the College is able to provide supports the surgeon-scientist specifically to maintain critically important research efforts and yet provide the essential patient care that is mandatory in our specialty.”

Pursuing funding opportunities, such as the awards supported by the ACS, requires perseverance.

“Apply and reapply. Never give up just because you’re not funded the first time,” advised Dr. Kindel. “It’s very rare, in today’s world of limited funding opportunities, to expect that you’re going to hit a home run the first time.”

Clinicians with a demonstrated track record for successfully obtaining funding typically share similar support systems, namely strong mentorship and guidance from leadership. Dr. Kindel advises early career surgeons in particular to avoid submitting an application before reviewing a colleague’s or mentor’s application for a similar type of grant.

“None of us knows how to do this right the first time and keep in mind each grant mechanism has a unique interest, mission, and value set. Young investigators should not rush a grant application. They should take the time to study their mentors’ success, as well as write and rewrite until they have a clear and concise grant application,” she said.

Dr. Kindel’s future research efforts—based on data related to the impact of bariatric surgery on the entire inflammatory state of the body, oxidative stress, and inflammatory cytokines—will assess the unique combination of gastrointestinal surgery with cognitive decline in obesity.

“We are interested in expanding our findings of sleeve gastrectomy in reducing oxidative stress to Alzheimer disease, a disease increased in patients with obesity and driven by oxidative damage,” Dr. Kindel shared. “We believe if we can treat midlife obesity and metabolic disease with bariatric surgery, we may have a very beneficial effect on long-term cognitive function and, hopefully, help people who are at risk for Alzheimer disease.”

To learn about the basic requirements and obligations associated with the Clowes Award, visit facs.org/clowes.

For more information about the ACS Foundation, the programs it supports, and how to contribute, go to facs.org/foundation.

Tony Peregrin is Managing Editor, Special Projects, in the ACS Division of Integrated Communications in Chicago, IL.

References

1. Medical College of Wisconsin. Dr. Tammy Kindel receives R01 grant to study cardiovascular impact of bariatric surgery. June 6, 2022. Available at: https://www.mcw.edu/news/dr-tammy-kindel-receives-r01-grant-to-study-cardiovascular-impact-of-bariatric-surgery. Accessed February 10, 2025.
2. Eckhouse SR, Ghanem OM. An Interview with Tammy Kindel, MD, PhD, FACS, FASMBS. Bariatric Times. February 1, 2023. Available at: https://bariatrictimes.com/interview-with-tammy-kindel/. Accessed February 10, 2025.
3. Patz JJ, Helm MC, Higgins RM, Goldblatt MI, Gould JC, Kindel TL. Peri-operative, intravenous clindamycin may improve the resolution rate of hypertension after Roux-en-Y gastric bypass in morbidly obese patients. Surg Endosc. 2019;33(12):3984-3989.
4. Juprasert JM, Marshall TE, Blood AG, Obeid L, Yeo HL. How to support a surgeon scientist: Lessons from National Institutes of Health K-Award recipients. J Surg Res. 2021;260(4):163-168.