# Exercise as it relates to Disease/Age-related effectiveness of endurance training as it relates to diastolic function in systolic heart failure patients

The following is a critical analysis of the paper: "Age-related effects of exercise training on diastolic function in heart failure with reduced ejection fraction: The Leipzig Exercise Intervention in Chronic Heart Failure and Aging (LEICA) Diastolic Dysfunction Study" (Marcus Sandri, Irina Kozarez, Volker Adams, Norman Mangner, Robert Hollriegel, Sandra Erbs, Axel Linke, Sven Mobius-Winkler, Joachim Thiery, Jurgen Kratzsch2, Daniel Teupser, Meinhard Mende, Rainer Hambrecht, Gerhard Schuler, and Stephan Gielen)

## What is the background to this research?

Diastolic dysfunction has been identified as an important predictor of increased mortality for patients who have experienced heart failure and often is an indication of reduced exercise capacity. The heart has trouble relaxing between breaths which limits the amount of blood the ventricles can collect. The impact being that with less oxygen rich blood being pumped with each contraction (< 40%), the heart is required to work harder. Diastolic left ventricular dysfunction is also influenced by a number of clinical factors including age, hypertension, obesity, and diabetes. The research paper hypothesises that endurance exercise training can improve diastolic dysfunction among heart failure patients with reduced ejection fraction (HFREF) and seeks to determine if the training is attenuated in older patients.

## Where is the research from?

This research paper was published in the European Heart Journal, a peer reviewed medical journal focussing on cardiology, and published by Oxford University Press on behalf of the European Society of Cardiology, a very reputable medical journal.
The papers primary author was Dr Stephan Gielen, a reputable researcher with over 238 papers to his name. This paper was co-authored by a number of researchers (15). Often the case where data collection and coordination is non-trivial as is the fact that collaboration among researchers is more the norm.
There were no conflicts of interest or bias declared. The study was supported by an unrestricted research grant of the Deutsche Forschungsgemeinschaft. A self-governing institution for the promotion of science and research.
The importance of this research lies in the age of the group tested as this enabled the researchers the ability to make an assessment on diastolic dysfunction in heart rate patients based on age and hence a predictor in quality of life based on a complimentary prescription of endurance exercise.

## What kind of research was this?

This study was conducted in the form of a prospective Randomised Control Trial (RCT), in which the HREF patients participating in the trial were first recruited based on categories relating to age (≤55 and ≥65) and then within the age group, randomly divided into either the training group participating in the endurance exercise intervention, or as an inactive control group for later comparison.
An RCT method of research is considered one of the most plausible ways of establishing a cause and effect relationship and generally accepted approach consistent within clinical interventions. Randomly allocating alike participants into a treatment or control group, helps to limit bias within the intervention itself or from those studies such as case controlled or observational studies where the outcome may be known and the study conducted is usually retrospective.

## What did the research involve?

The study involved the 120 participants, 60 were healthy and 60 with HFREF. Once divided into age groups, half assigned an endurance exercise training program whilst those not assigned the program remained the control group.
The exercise intervention consisted of four supervised training sessions per week each for 20 minutes followed by a 60-minute recreation session.
Primary outcome measures involved the measurement of improved functional exercise capacity (through cardiopulmonary exercise testing) and the subjects left ventricular diastolic function as assessed by tissue Doppler (E/E' ratio).
The same echocardiographer was used for all measurements and was blinded to the patient status to remove any bias.
There are some limitations to the research worth noting:
* Patients with HFREF were recruited based on referral to a single center. Therefore, patients in the study may not be representative of the entire HFREF population.
* The patients were taking normal medications throughout the process which may have altered the potential of results via beta-blockers, some medications can influence heart rate.
* Given the disparate ages in the control group, common age related diseases such as hypertension and dyslipidemia were identified which can have an effect on exercise using max heart rate as a measure of effort.

## What were the basic results?

Diastolic Functional Assessment
* Endurance training is highly effective in improving left ventricular diastolic function in HFREF patients regardless of age.
* Reduction of LV isovolumetric relaxation time by 29% in young and by 26% in old.
* As assessed by tissue Doppler, septal E′ increased by 37% in young and by 39% among old
* significant decrease in the E/E′ ratio from 13±1 to 10±1 in young and 14±1 to 11±1 in old.
Exercise Functional Assessment
* Maximal exercise capacity in the control group increased by 30% in the younger and 31% in the older.
* Maximal oxygen uptake increased by 14% in the younger and 19% in the older.
* In HFREF subjects, maximal exercise capacity increased by 31% in the younger and 37% in the older.
* Maximal oxygen uptake increased by 26% in the younger and by 27% in the older.
The researchers presented a very clinical approach to their analysis and did not over-emphasise the results. They proved the physiological benefits of the endurance exercise intervention on patients with and without the HFREF condition not just with before and after testing but with paired data testing. To complete the analysis of findings it would have been beneficial to better understand the recommendation on research next steps regarding the potential physiological benefits for the higher risk patients that were initially removed from the trial and to broaden the trial to a larger more representative population.

## What conclusions can we take from this research?

There is no doubting the benefits of physical exercise as a compliment to modern medicine. The intervention quantitatively proves the success of endurance exercise for HFREF and control patients. The older age group that were used as the control group that showed symptoms of age-related disease also showed markable improvement. As these life diseases are common, it would be helpful to further the research to demonstrate the benefits more quantitatively. A wholistic approach to research would ensure that health span and its relationship to lifespan and age-related diseases is understood.

## Practical advice

As evidenced in this review and recent studies, endurance-based training provides significant benefit to cardiovascular health, particularly diastolic heart function and should be considered, within a controlled setting, an integral part of any patient recovery or exercise program.
* Aerobic programs that encourage lower intensity social activities would benefit all participants regardless of pre-existing conditions and could assist with intrinsic motivation to adopt more permanent change.
* Examples include walking, jogging, dancing and biking.
* Seeking advice from your doctor or allied health professional is critical to ensure you're following a safe and effective program.
Keep an eye out for warning signs of heart attack such as chest discomfort, shortness of breath or other signs such as cold sweat, nausea or light headedness. Refer to Heart foundation's recovery support and resources section for further information heart foundation my-heart-my-life

## Further information/resources

For further information on the benefits of endurance training as it relates to your heart, below are some additional resources that would be considered useful.
* Heart foundation
* Exercise based rehabilitation
* Chronic Heart disease and exercise
* Australian Allied Health Professionals
* Exercise and Sports Science Australia
* Exercise right

## References

* ↑ [Sandri M, Kozarez I, Adams V, Mangner N, Höllriegel R, Erbs S, Linke A, Möbius-Winkler S, Thiery J, Kratzsch J, Teupser D. Age-related effects of exercise training on diastolic function in heart failure with reduced ejection fraction: the Leipzig Exercise Intervention in Chronic Heart Failure and Aging (LEICA) Diastolic Dysfunction Study. European heart journal. 2012 Jul 1;33(14):1758-68.]
* ↑ [Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, Meverden RA, Roger VL. Systolic and diastolic heart failure in the community. Jama. 2006 Nov 8;296(18):2209-16]
* ↑ [Forman DE, Clare R, Kitzman DW, Ellis SJ, Fleg JL, Chiara T, Fletcher G, Kraus WE, HF-ACTION Investigators. Relationship of age and exercise performance in patients with heart failure: the HF-ACTION study. Am Heart J 2009;158(4 suppl):S6–S15]
* ↑ [Baethge C. Publish together or perish: the increasing number of authors per article in academic journals is the consequence of a changing scientific culture. Some researchers define authorship quite loosely. Deutsches Arzteblatt International. 2008 May;105(20):380.]
* ↑ [Ford I, Norrie J. Pragmatic trials. New England journal of medicine. 2016 Aug 4;375(5):454-63.]
* ↑ [Ware JH, Hamel MB. Pragmatic trials — guides to better patient care? N Engl J Med 2011; 364: 1685-7.]
* ↑ [Petrisor BA, Bhandari M. The hierarchy of evidence: levels and grades of recommendation. Indian journal of orthopaedics. 2007 Jan;41(1):11]
* ↑ [Lurje L, Wennerblom B, Tygesen H, Karlsson T, Hjalmarson Å. Heart rate variability after acute myocardial infarction in patients treated with atenolol and metoprolol. International journal of cardiology. 1997 Jun 25;60(2):157-64.]
* ↑ [Wonisch M, Hofmann P, Fruhwald FM, Kraxner W, Hödl R, Pokan R, Klein W. Influence of beta-blocker use on percentage of target heart rate exercise prescription. European Journal of Cardiovascular Prevention & Rehabilitation. 2003 Aug;10(4):296-301.]
* ↑ [Edelmann F, Bobenko A, Gelbrich G, Hasenfuss G, Herrmann‐Lingen C, Duvinage A, Schwarz S, Mende M, Prettin C, Trippel T, Lindhorst R. Exercise training in Diastolic Heart Failure (Ex‐DHF): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial. European journal of heart failure. 2017 Aug;19(8):1067-74.]
* ↑ Bowen TS, Herz C, Rolim NP, Berre AM, Halle M, Kricke A, Linke A, Da Silva GJ, Wisloff U, Adams V. Effects of endurance training on detrimental structural, cellular, and functional alterations in skeletal muscles of heart failure with preserved ejection fraction. Journal of Cardiac Failure. 2018 Sep 1;24(9):603-13.]