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Cancer Warriors losing battle to heart disease?

Your cancer treatment may be over, but does it continue to cause side effects to your body? Chemotherapy and radiation have revolutionized the survival rates among cancer patients, but so is the development of cardiovascular diseases (CVD) in cancer survivors. The scientific session 2021 program committee organized an educational session on cardio-oncology, which included talks by experts on heart health after cancer treatment, feedback link between heart and cancer, racial disparities, and new clinical imaging technology. The session was moderated by Dr. Susan Gilchrist from Houston, TX, Dr. Daniel Addison from Columbus, OH, and Dr. Mary Branch from Oak Ridge, NC. However, my favorite part was a short talk by Ms. Kikkan Randall, the first American cross-country skier to win Olympic gold along with her teammate. The session walked through the science journey and a patient journey and provided us perspective on a healthy heart from both expert’s and patient’s point of view.

Cardiovascular diseases are the leading non-cancerous cause of death among cancer survivors. Cardiac dysfunction, atherosclerosis, arrhythmia, and valvular diseases are major complications observed among cancer survivors. The first speaker in the cardio-oncology session was Dr. Saro Armenian from the City of Hope Comprehensive Cancer Center. He started by discussing the nature of the problem using the “Multiple-Hit” hypothesis, where he discussed how the margin of safety declines following cancer diagnosis and treatment. He further addressed the effect of tumor and cancer therapies on cardiac output, pulmonary function, muscle integrity, and oxygen-carrying capacity, all events ultimately causing cardiovascular aging among patients. He further walks us through how clonal hematopoiesis (a condition where we accumulate somatic mutation in the blood) can be the underlying cause of cardiovascular aging and drive CVD development among cancer patients. You can further read about clonal hematopoiesis and premature aging in one of his publications:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192097/

After a fantastic talk on premature cardiovascular aging in cancer patients, Dr. Clyde Yancy provided an exciting perspective on racial disparities. Adverse differences in numerous cancer burdens exist among specific population groups in the United States. For example, African American men are 111% more like to develop prostate cancer, whereas American Indian/Alaska Natives are twice as likely to develop liver and bile duct cancer. Similarly, racial, and ethnic health care disparities are present in cardio-oncology due to structural racism, higher prevalence of CVD risk factors, and reduced access to specialty care. A multidisciplinary approach involving stakeholders, health care policymakers, clinicians, scientists, and patients is required to resolve these disparities. Lastly, Dr. Clyde Yancy highlighted the importance of diverse population-based study and, in addition to genetic factors, phenotyping the social determinants of CV health. Read one of his recent publications about how poverty can increase the risk of heart problems:

https://pubmed.ncbi.nlm.nih.gov/34240286/

The third talk was from Dr. Rudolf A. de Boer from University Medical Center Groningen about reverse cardio-oncology. When I think about cardio-oncology, I always think about how cancer patients end up developing heart problems. However, he explained how the reverse could be true. He shared preclinical findings on how heart failure promotes tumor growth. Both CVD and cancer share several risk factors. Further, angiogenesis and inflammation under CVD conditions can increase the risk of tumor development. To learn more about cardio-oncology, refer to his recent review: https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013754

There were additional highlights on crosstalk on clinical imaging by Dr. Ana Barac from MedStar Heart. She listed the importance of cardiac imaging, echocardiography, and cardiac MRI.

Lastly, Olypoam Kikkan Randall, a cancer survivor, shared how she stayed committed to the 10-minute rule to keep her active despite adversity. Exercise training has been shown to confer beneficial effects in cancer patients at CVD risk. Here is an interesting article documenting a scientific statement from AHA for cancer survivors to manage cardiovascular outcomes. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000679

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Cardio-Oncology, Meet Your New Neighbor: Immunology

In this AHA session, an international group of physician scientists discussed ways to mitigate immune checkpoint inhibitor (ICI) induced myocarditis and future therapies. The session, moderated by Dr. Sakima Smith MD, MPH, FAHA (from THE Ohio State), and Dr. Doug Tiley highlighted studies by Drs. Burkhard Ludewig, DVM, Dr. Han Zhu, MD, Dr. Alcaide, PhD, Dr. Peter Liu, MD and Dr. Joe-Elie Salem, MD, PhD. The talk began with presenting the problem, basic-science T-cell mechanisms including involvement of microbiota, and ended with a possible targeted therapy, Abatacept. This is a hot topic in the cardio-oncology world considering the high mortality in those affected (up to 50%!) [1].

Source: Cardio-Oncology, Meet Your New Neighbor: Immunology| American Heart

ICIs (eg. ipilimumab, pembrolizumab) are effective targeted therapies in patients with PDL-1/PD-1 expression on tumor cells. Many cancer phenotypes are FDA approved for treatment which includes melanoma, renal cell carcinoma, non-small-cell lung cancer, Hodgkin lymphoma, and more[2]. Although these agents have shown to extend cancer survivorship[3] , they have inadvertent side effects that can lead to myocarditis and cardiomyopathy. ICIs act by “releasing the brake” of T cell immune proliferation. These monoclonal antibodies block PD1/PDL-1 ligands/receptors and allow for T cells to bind to tumor cells leading to reduced tumor burden[3]. Understanding the mechanism for ICI induced myocarditis is partially based on PDL1 knockout mice[4]. Unfortunately, there is cross-reactivity that occurs via binding to cardiac antigens (eg. myosin) leading to the inflammatory response[4].

Dr. Zhu informed us that the risk of this effect includes dual ICI treatment. In addition, early identification is key, considering 50% mortality. Patients may have a drop in their ejection fraction (EF), but have other signs of cardiac injury including brady and tachyarrhythmias. She highlighted that our current data is from FDA sponsored pharmacovigilance databases collected by Dr. Javid Moslehi, who is a pioneer and leading investigator on this subject. A registry created by Dr. Tom Neilan’s lab at Massachusetts General Hospital demonstrated an increased risk of MI and stroke after treatment with ICI[5]. Her group at Stanford along with renowned Dr. Ronald Witteles is using biobanking to identify patients with autoimmune myocarditis and controls to conduct downstream high-throughput immune repertoire analysis. Dr. Alcaide supplemented this talk by adding a novel mechanism. She discussed that reactive oxygen species (ROS) play a role in triggering downstream T cell expansion in the heart. Therefore, there may be a role in anti-oxidant therapy to reduce T cell response. Dr. Liu acknowledged our current pandemic and discussed the added risk of inflammation in the setting of concomitant COVID19 viral infection associated with myocarditis.

During this session, we learned about possible therapies to mitigate myocarditis. Dr. Ludewig discussed his teams work with an ICI mouse model. They explored T cell cross-reactivity that led to the lethality of the disease. There was a heart-gut connection! They found elevation of Bacteroides-specific CD4+ T cells in disease models which suggests that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible patients (those with HLA DQB1*03:01 polymorphisms) by showing increased reactivity against myosin 6 (MYH6) (cardiac antigen). His study suggests that the genetic susceptibility along with cross-reactivity antigens in the heart and potentially the intestine put patients at risk for fulminant myocarditis. Therefore, he proposed the use of antibiotics as a cardioprotective agent by blocking the cross-reactivity that leads to ICI induced myocarditis.

Source:  Ludewig: ‘Dangerous gut-heart liaison’| When it comes to matters of the heart, don’t always trust your gut/ Cruz et al. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science 2019; 336, 881-886.

Dr. Joe Elie-Salem (making us jealous by Zooming in from Paris; Ca alors!) ended the session with the introduction of abatacept for therapeutic use in ICI induced myocarditis.  Corticosteroids are the mainstay of treatment; however steroid therapy is nonspecific and there are unintended off-target side effects. Specifically, there is a high association with concurrent myasthenia gravis-like syndrome with ICI myocarditis that presents a challenge with the use of steroids. Steroids can lead to an exacerbation of myasthenia crisis which can lead to significant respiratory failure[6].  Based on work with Dr. Moslehi, abatacept (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] agonist, they found that in anti-CTLA4 and Anti—PDL-1  treated disease mouse models, treatment with abatacept reduced myocarditis induced death. This agent will be further explored in a Phase II trial titled: ACHLYS-trial: Phase II trial testing abatacept for ICI-myocarditis.

The take-home points for this session include: 1) ICI used to treat many cancer phenotypes are associated with incident myocarditis with up to 50% mortality 2) Cross-reactivity with cardiac antigens leads to myocyte dysfunction and the clinical sequelae of this includes cardiomyopathy (not always!) and brady/tachyarrhythmias 3) Understanding predisposing immune variants and microbiota (Bacteroides- B. theta) related to immune response associated with this disease is key to identifying all the possible therapies including antibiotics 4) Abatacept is a known T cell immunomodulator and it has a potential role in treating ICI induced myocarditis; especially in those at risk for corticosteroid effects (eg. myasthenia gravis), which will be further explored in a clinical trial.

REFERENCE

  1. Ball, S., et al., Cardiovascular Toxicities of Immune Checkpoint Inhibitors: JACC Review Topic of the Week. J Am Coll Cardiol, 2019. 74(13): p. 1714-1727.
  2. Zhou, Y.W., et al., Immune Checkpoint Inhibitor-Associated Cardiotoxicity: Current Understanding on Its Mechanism, Diagnosis and Management. Front Pharmacol, 2019. 10: p. 1350.
  3. Ferris, R.L., et al., Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med, 2016. 375(19): p. 1856-1867.
  4. Nishimura, H., et al., Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 2001. 291(5502): p. 319-22.
  5. Drobni, Z.D., et al., Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque. Circulation, 2020.
  6. Xing, Q., et al., Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma. Ann Transl Med, 2020. 8(5): p. 250.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Why Cardiology?

“Why Cardiology?” is one of the most common questions I have been asked by friends, family, interns, residents, and even the occasional stranger sitting next to me on a flight. Despite being a simple question, the answer is very complex. I initially started residency thinking I would pursue a career in pulmonary/critical care – I loved the acuity, broad differential diagnoses, and the bond created with families. However, after my first month in the unit, I quickly abandoned this career path for multiple reasons. Shortly thereafter, I did my first rotation on the cardiology wards service with Dr. Matthew McGuiness (who is still one of my closest mentors) and I saw the light.

The month on the cardiology wards service is best described as “finding the missing piece of the puzzle.” I loved the anatomy, physiology, patient population, subtle differences in presentations, and my interactions even as an intern with patients. I also loved the depth of cardiology – including both clinical and basic science research opportunities, advanced fellowships options, and the ability to create my niche in cardiology. I learned cardiologists were pursuing careers in preventative cardiology, cardio-oncology, cardiac critical care, and cardio-obstetrics. I was blown away at the possibilities of a career in cardiology and having the ability to create my perfect dream job.

As I mentioned earlier, I was very interested in critical care when I started residency but did not want to be in the medical ICUs. The cardiac intensive care units were much more interesting to me with advanced hemodynamics, malignant arrhythmias, various mechanical circulatory devices, and seeing how quickly the realm of the cardiac ICUs were changing. The CCUs are no longer filled with patients who have had a STEMI requiring a week-long admission, but rather those with decompensated heart failure/cardiogenic shock requiring mechanical circulatory support (MCS) with LVADs, Impella, or ECMO.

I am now combining all of my loves – cardiology, critical care, and obstetrics (yes, I at one point wanted to go into OBGYN) for my job as an attending. With the help of my mentors, I have been able to combine all my passions into one. I will be attending in the cardiac intensive care unit and have a predominantly general cardiology clinic with a focus on cardio-obstetric patients. And the best part, every cardiology fellow can create his/her dream job.

A few key questions to ask yourself are:

  • Do I see myself as someone who enjoys the in-patient or the out-patient setting? This will help focus career options and set the stage for your career.
  • Am I a proceduralist or not? For me, I hate wearing lead, so it was a simple decision to not go into interventional or EP.
  • What type of patients do I get the most joy of taking care of. In my case, it was the critically ill and women who are pregnant with cardiovascular disease.
  • Who is 5-10 years ahead of me career-wise and has my ideal job? This has helped me be more active with research, clinics, conferences, and improve my fund of knowledge. It also gave me a roadmap to follow – no need to reinvent the wheel.

Of course, these are starting points and it’s a vast topic that takes time to explore. My journey of “why cardiology” has been filled with highs and low, but with the help of various mentors I have a clear vision of what I envision for my future career.

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Artificial Intelligence in Cardiology: Opportunities for Cardio-Oncology

History was made recently with the inaugural and first ever continuing medical education conference on artificial intelligence (#AI) in Cardiology. While most of the presentations were on artificial intelligence or cardiology or both, several sessions also made reference to other fields in which AI has been or is being used, such as Oncology. There was even one study presented on Cardio-Oncology. As study after study was presented, it became clear to me that perhaps several of these techniques and methodologies could potentially be useful to our patients in Cardio-Oncology.

Every single piece of technology started with one single prototype. Every single new piece of software started with one single algorithm. Every single patent started with one single idea. Every single idea started with the impact that disruptive technology could have for at least one single patient – one single case.

As I view various case reports in Cardio-Oncology, I think about how #AI could influence care delivery to potentially improve outcomes and the experience for each patient and their health professionals.

One example that was reiterated in multiple presentations was that of the ECG. Applying #AI to the ECG has been shown in the studies presented to determine the age, sex, and heart condition of the individual. Details were shown for a case of hypertrophic cardiomyopathy (yes, HCM, not just left ventricular hypertrophy) diagnosed via #AI analysis of an ECG that appeared relatively unremarkable to physicians’ eyes. After the septal surgery/procedure, although the ECG then looked remarkably abnormal to physicians’ eyes, the #AI algorithm could identify resolution of the hypertrophic cardiomyopathy.

Another example reiterated throughout the conference was identifying undiagnosed left ventricular systolic dysfunction, in a general community population and also in patients referred to a cardio-oncology practice at a large referral center.

Recently, #AI in Cardiology has been used most frequently for monitoring and detection of arrhythmias, such as atrial fibrillation. Everyone can purchase their own wearable to determine this. Physicians are also now prescribing these wearables for ease-of-use, given their pervasive presence and coupling with smartphones owned by much of the population or provided temporarily by the physician group. Such wearables are transitioning from standalone electrodes, to watches, skin patches, and clothing (e.g., shirts, shorts).

Many direct-to-consumer #AI applications in daily life actually are not wearable, such as Alexa and Siri. One study described the ability of #AI to help diagnose mood disorders and cardiac conditions and risk factors by simply “listening to” and analyzing voice patterns. The timing of a young man’s “voice breaking” can potentially predict his risk for heart disease!

A popular use for #AI in medicine overall is to assist with interpretation of various imaging, such as chest X-rays, MRIs, or CT scans. This applies in Cardiology as well. Further, in Cardiology, #AI is being used to help guide the procurement of echocardiograms. The algorithms provide visual instructions (such as curved arrows) to indicate directions in which the ultrasound probe should be moved to obtain the standard view, to which the algorithm is comparing the image being procured moment-by-moment. The idea is for #AI to help less experienced sonographers or echocardiographers learn and perform echocardiography even more expediently.

The theme of the conference was current advances and future applications of #AI in Cardiology. Accordingly, a historical perspective was given, describing some of the earliest attempts at #AI in various fields. A video of a possible precursor to current automated vacuum cleaners was shown, from archives dating back to the 1960s. In addition to ways in which #AI is now being studied or applied, future opportunities for using #AI were also postulated, for example for coronary artery disease, since stress tests are not 100% sensitive and the gold standard coronary angiography is invasive. #AI could help stratify patients who needed versus did not need the invasive procedure for recurrent convincing symptoms in the absence of a positive stress test. Of course, coronary CT angiography could help fill this gap, but #AI might assist with decision-making sooner.

There have been studies on #AI in Cardiology, and studies on #AI in Oncology, and at least one study in #AI in Cardio-Oncology – a study I predicted; one that is quite intuitive and mentioned above. I propose that we continue to apply #AI in Cardio-Oncology, so that the field can catch up with the rest of Cardiology and Oncology, and help us continue to develop this emergent and burgeoning multidisciplinary subspecialty.

This is an exciting time for me to be alive. I am an early adopter of artificial intelligence. I look forward to seeing more and more the availability of #AI to enhance our use of electrocardiography, echocardiography, wearables, biosensors, voice analysis, and more in Cardiology, and particularly in Cardio-Oncology, with an emphasis on primary and primordial prevention even before secondary and tertiary prevention in the area of Preventive Cardio-Oncology, and especially in women.

 

 

 

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Preventive Cardio-Oncology: The Role Of High Intensity Interval Training

Heart disease is the number one killer of survivors of cancer1, 2, 3. It is our responsibility to help our patients with cancer understand and mitigate this risk. Prevention of heart disease in these patients should occur at three stages: in Cardio-Oncology prehabilitation2, 4, habilitation2, 4, and rehabilitation2, 4, 5. At all three stages, exercise is a key component and can be optimized with consideration of high intensity interval training (HIIT).

HIIT has emerged as an exercise structure that adds more efficiency and power to typical continuous exercise regimens. Studies in the general population suggest that HIIT is safe and non-inferior or superior to continuous exercise regimens in its effect on fitness6, 7, lipids7, 8, blood pressure9, blood glucose levels9, waist circumference8, body fat percentage7, 8, insulin resistance7, and more. Beneficial findings and safety have also been reported for individuals with cardiovascular disease (including coronary artery disease and heart failure)10, as well as cancer11.

The format of HIIT is just as it sounds – incorporating high intensity intervals into exercise training. This is not necessarily training for marathons, sprints, or triathlons. This is training for life. Life that individuals with cancer fight so hard for. We owe it to these individuals to help them live their best life when their cancer is in remission. Part of that is their best heart health, and incorporating heart-healthy behaviors most seamlessly into their daily lives. One safe, effective, and efficient way to do that is with HIIT. In HIIT, following warmup individuals work out at high intensity for 30-120 seconds, then either rest or work out at low/moderate intensity for 30-120, alternating between the two for the duration of their set-aside exercise time or program. For example, an individual on a bicycle would cycle at 10 mph for 30-120 seconds, then at 0 or 5-9 mph for 30-120 seconds, alternating between the two for the duration of their set-aside exercise time or program. The new physical activity and prevention of cardiovascular disease guidelines provide great additional examples of moderate versus high intensity aerobic exercises12, 13.

A recent article suggested that HIIT may be the answer to meeting the needs of women in cardiac rehabilitation14. Indeed, HIIT may also be part of the solution to meeting the needs of women in Cardio-Oncology prehabilitation, habilitation, and rehabilitation. Yet for several years, clinicians and researchers have noted a myriad of barriers faced by women in cardiac rehabilitation14, 15, and that a plethora of women are not referred to cardiac rehab at all15. Besides time and accessibility limitations, other reported barriers include lower education level, multiple comorbid conditions, non-English native language, lack of social support, and high burden of family responsibilities. It should therefore be noted that while HIIT may serve as part of the answer to meeting the needs of women in cardiac rehabilitation or in Cardio-Oncology prehabilitation, habilitation, and rehabilitation, other solutions will be needed to address the variety of barriers unrelated to time and accessibility. The use of automatic referral and assisted enrollment can improve the participation of women in cardiac rehabilitation15, while incentive-based strategies and home-based programs may enhance program completion15. Additional solutions will be needed to address remaining barriers, such as health literacy related to lower education level, multiple comorbidities, non-English native language, high burden of family responsibilities, and of course adverse effects of cancer therapies.

As we step out into and carry on in our Early Careers, it is important for us to be aware of high intensity interval training and its incredible potential to elevate our care of women and men in cardiac rehabilitation in Preventive Cardiology, as well as in Cardio-Oncology prehabilitation, habilitation, and rehabilitation.

References
1. Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz-Flores S, Dent S, Kondapalli L, Ky B, Okwuosa T, Piña IL, Volgman AS; American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association. 2018 Feb 20;137(8):e30-e66. doi: 10.1161/CIR.0000000000000556. Epub 2018 Feb 1.

2. Squires RW, Shultz AM, Herrmann J. Exercise Training and Cardiovascular Health in Cancer Patients. Curr Oncol Rep. 2018 Mar 10;20(3):27. doi: 10.1007/s11912-018-0681-2.

3. Patnaik JL, Byers T, DiGuiseppi C, Dabelea D, Denberg TD. Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study. Breast Cancer Res. 2011 Jun 20;13(3):R64. doi: 10.1186/bcr2901.

4. https://earlycareervoice.professional.heart.org/preventive-cardio-oncology-the-rise-of-prehabilitation/. Accessed April 20, 2019.

5. Gilchrist SC, Barac A, Ades PA, Alfano CM, Franklin BA, Jones LW, La Gerche A, Ligibel JA, Lopez G, Madan K, Oeffinger KC, Salamone J, Scott JM, Squires RW, Thomas RJ, Treat-Jacobson DJ, Wright JS; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Peripheral Vascular Disease. Cardio-Oncology Rehabilitation to Manage Cardiovascular Outcomes in Cancer Patients and Survivors: A Scientific Statement from the American Heart Association. Circulation. 2019 Apr 8:CIR0000000000000679. doi: 10.1161/CIR.0000000000000679. [Epub ahead of print].

6. Su L, Fu J, Sun S, Zhao G, Cheng W, Dou C, Quan M. Effects of HIIT and MICT on cardiovascular risk factors in adults with overweight and/or obesity: A meta-analysis. PLoS One 2019 Jan 28;14(1):e0210644. doi: 10.1371/journal.pone.0210644. eCollection 2019.

7. Fisher G, Brown AW, Bohan Brown MM, Alcorn A, Noles C, Winwood L, Resuehr H, George B, Jeansonne MM, Allison DB. High Intensity Interval- vs Moderate Intensity- Training for Improving Cardiometabolic Health in Overweight or Obese Males: A Randomized Controlled Trial. PLoS One 2015 Oct 21;10(10):e0138853. doi: 10.1371/journal.pone.0138853. eCollection 2015.

8. Stavrinou PS, Bogdanis GC, Giannaki CD, Terzis G, Hadjicharalambous M. High-intensity Interval Training Frequency: Cardiometabolic Effects and Quality of Life. Int J Sports Med. 2018 Feb;39(3):210-217. doi: 10.1055/s-0043-125074. Epub 2018 Feb 2.

9. Batacan RB Jr, Duncan MJ, Dalbo VJ, Tucker PS, Fenning AS. Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies. Br J Sports Med. 2017 Mar;51(6):494-503. doi: 10.1136/bjsports-2015-095841. Epub 2016 Oct 20. Review.

10. Wewege MA, Ahn D, Yu J, Liou K, Keech A. High Intensity Interval Training for Patients With Cardiovascular Disease—Is It Safe? A Systematic Review. J Am Heart Assoc. 2018 Nov 6;7(21):e009305. doi: 10.1161/JAHA.118.009305.

11. Mugele H, Freitag N, Wilhelmi J, Yang Y, Cheng S, Bloch W, Schumann M. High-intensity interval training in the therapy and aftercare of cancer patients: a systematic review with meta-analysis.
Mugele H, Freitag N, Wilhelmi J, Yang Y, Cheng S, Bloch W, Schumann M.
J Cancer Surviv. 2019 Apr;13(2):205-223. doi: 10.1007/s11764-019-00743-3. Epub 2019 Feb 26. Review.

12. Piercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, George SM, Olson RD. The Physical Activity Guidelines for Americans. JAMA. 2018 Nov 20;320(19):2020-2028. doi: 10.1001/jama.2018.14854.

13. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
J Am Coll Cardiol. 2019 Mar 17. pii: S0735-1097(19)33876-8. doi: 10.1016/j.jacc.2019.03.009.

14. Way KL, Reed JL. Meeting the Needs of Women in Cardiac Rehabilitation. Circulation. 2019; 139(10):1247–1248.

15. Supervía M, Medina-Inojosa JR, Yeung C, Lopez-Jimenez F, Squires RW, Pérez-Terzic CM, Brewer LC, Leth SE, Thomas RJ. Cardiac Rehabilitation for Women: A Systematic Review of Barriers and Solutions. Mayo Clin Proc. 2017 Mar 13. pii: S0025-6196(17)30026-5. doi: 10.1016/j.mayocp.2017.01.002. [Epub ahead of print] Review.

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Preventive Cardio-Oncology: A Role For Cardiopulmonary Stress Testing

Cardiopulmonary exercise stress testing can be useful in a variety of ways, particularly for Preventive Cardiology and Preventive Cardio-oncology. The test helps to assess for levels of fitness, causes of functional limitation, and evidence of ischemia. Test results can be used to counsel individuals, guide exercise prescriptions, and reassure, encourage, and motivate individuals for lifestyle modification and behavior change.

The exercise ECG portion of the test gives information regarding evidence of ischemia, exercise capacity, and adequacy of heart rate response, and response of blood pressure to exercise. The information of this portion of the test can help to determine whether there are any high-risk cardiac features that need to be addressed, such as evidence of ischemia or hypotensive response to exercise. Limited heart rate response is also useful to help determine whether rate-limiting medications or pacemaker settings need to be adjusted. Often, when medications like metoprolol or pacemaker heart rate response are adjusted, this can improve the function and experience of patients who are previously limited by their heart rate during activity. The exercise capacity information given by the exercise ECG, such as excellent, good, average, below average, fair, or poor can give an indication of individuals’ ability to meaningfully, safely, and successfully pursue exercise. Oftentimes, some patients who have had prior cardiovascular events may shy away from moderate or intense exercise for fear of cardiovascular injury as a result of exertion. Pursuing an exercise ECG portion of the cardiopulmonary stress test can help individuals in such cases recognize that they can perform moderate or intense exercise safely without injuring their heart. The exercise capacity reported on the test can help these individuals see that their exercise or aerobic capacity is poor because of their hesitation to pursue moderate or intense exercise. This can be motivating for individuals to recognize that they can benefit from doing more and that they can do more safely. This is particularly the case for individuals who have experienced a cardiovascular event from spontaneous coronary artery dissection, which does not have many modifiable risk factors, and understandably leads to apprehension in young women diagnosed with this condition. However, the exercise ECG portion alone lacks several informative parameters important for patient care in Preventive Cardiology and Cardio-Oncology.

The specific addition to the test provided by the ‘cardiopulmonary’ portion involves oxygen consumption. If oxygen consumption (or VO2) is below average, limited, or poor, there can be several reasons for this. The most common reasons include cardiac impairment, pulmonary impairment, deconditioning, excess weight, and limited heart rate reserve. There are various parameters in the cardiopulmonary stress test results that will indicate whether deconditioning plays a role, whether BMI plays a role, whether cardiac impairment plays a role (in which case this could be due to low flow from systolic dysfunction or due to diastolic dysfunction or even heart rate), or whether pulmonary impairment plays a role (which could be of varied etiology). This addition to the test also helps patients to objectively see data supporting the suspicion that they have become deconditioned after a cardiovascular event or after cancer therapies. They get to see that the cancer therapies or their subsequent levels of activity following their cardiovascular event could currently or potentially affect their function, and may explain any current functional limitation or in fact set them up for functional limitation going forward. The test can also help patients see the effect of any excess weight on their compromised oxygen consumption. Given that cancer therapies for breast cancer, for example, will often include radiation, surgery, and chemotherapy that can injure the heart and/or the lungs, it is helpful to determine the suggested underlying causes of functional limitation as assessed by oxygen consumption in these patients who have had treatment involving the chest. Performing the cardiopulmonary stress test at baseline before treatment helps individuals see their level of fitness, deconditioning, weight effect, cardiac impairment, or pulmonary impairment, even before ever undergoing cancer therapy. Given that fitness levels and injuries to the heart or the lungs can be affected by cancer therapies, then repeating the test after therapies can show patients the change that has occurred as a response to therapies. This can be helpful for patient to have a sense of their original baseline and goals that they can work towards to supersede even that baseline. For individuals who are not going to undergo cancer therapies, obtaining a baseline also helps individuals with a sense of how much they could potentially achieve. Then, once they have achieved a particular goal, the test can be repeated to show the improvement and continue to inspire motivation. This objective collection of evidence and data that can be used for motivation, reassurance, counseling, and exercise prescription is all key for lifestyle modification and behavior change in Preventive Cardiology and Preventive Cardio-Oncology. Thus, for all these reasons and more cardiopulmonary stress testing will evolve to play a large role in Cardio-Oncology prehabilitation, habilitation, and rehabilitation1,2,3, as we help individuals prepare for, experience well, and long outlive their cancer therapies.

 

References

  1. https://earlycareervoice.professional.heart.org/preventive-cardio-oncology-the-rise-of-prehabilitation/. Accessed April 20, 2019.
  2. Squires RW, Shultz AM, Herrmann J. Exercise Training and Cardiovascular Health in Cancer Patients. Curr Oncol Rep. 2018 Mar 10;20(3):27. doi: 10.1007/s11912-018-0681-2.
  3. Gilchrist SC, Barac A, Ades PA, Alfano CM, Franklin BA, Jones LW, La Gerche A, Ligibel JA, Lopez G, Madan K, Oeffinger KC, Salamone J, Scott JM, Squires RW, Thomas RJ, Treat-Jacobson DJ, Wright JS; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Peripheral Vascular Disease. Cardio-Oncology Rehabilitation to Manage Cardiovascular Outcomes in Cancer Patients and Survivors: A Scientific Statement from the American Heart Association. Circulation. 2019 Apr 8:CIR0000000000000679. doi: 10.1161/CIR.0000000000000679. [Epub ahead of print].
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The Emergence of The Field of Cardio-Oncology

By 2026, it is anticipated that there will be more than 20 million cancer survivors in the US1. The increase in prevalence of cancer survivors is largely due to discovery and implementation of effective chemotherapeutics and radiation therapy.  This success has come with a price, however, as the same chemotherapeutics and radiation therapy that cure cancer also damage vital organs, such as the heart. A wide range of chemotherapeutics have been associated with coronary artery disease, pericardial disease, and thromboembolic disease. Radiation therapy may accelerate premature atherosclerosis through acute inflammation leading to early vasculopathy in irradiated regions. With the introduction of each effective novel agent in treatment that prolongs survival,  side effects may  affect patient health and quality of life.

These factors have prompted the newly published AHA Scientific Statement on the field of Cardio-oncology, focused on the vascular and metabolic ramification of cancer treatment2. Cardio-oncology is a rapidly growing field of study given the prevalence of cancer and the need for physicians to address the unique challenges of treatment of cardiovascular disease in the cancer population.

Similar to general cardiology, prevention is a vital aspect of the field of cardio-oncology. This is due to the fact that both detection and treatment of cardiotoxicity is difficult. Symptomatically, cardiotoxicity can take years to manifest with the use of certain chemotherapeutics  and detection of subclinical cardiotoxicity is challenging. Thus, monitoring and screening become the most effective ways to minimize risk of development of cardiotoxicity and vascular complications.

Care in the cancer population should be multi-disciplinary from the moment the decision is made on the chemotherapeutics/radiation cycle to be used in treatment. Oncologist, cardiologists, and primary care physician are a vital part of care and must work together to make sure patients are medically optimized before start of treatment regimens. This includes thorough risk stratification and analysis of the benefits of treatment modalities, which needs to be individualized. Demographic factors such as the patient’s family history, prior cardiac history, current exercise tolerance are important factors to consider. Identification of patients at high risk would allow for consideration of alternative therapy, closer monitoring, screening, and possibly prophylactic treatment with cardioprotective medications. These patients can be monitored closely and undergo regular screening for signs of ventricular dysfunction.

Cardio-oncology is an exciting field of study with many unanswered questions. As literature continues to grow, I hope that we can meet the many challenges of cancer treatment.

 

References:

  1. Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. 2016. Cancer treatment and survivorship statistics. CA: A Cancer Journal for Clinicians 66 271–289.
  2. Campia U, Moslehi JJ, Amiri-kordestani L, et al. Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association. Circulation. 2019;139(13):e579-e602.