Cardiovascular Ultrasound - Latest Comments

REVERSAL OF DIASTOLIC DYSFUNCTION IN TYPE 2 DIABETICS AFTER EXERCISE TRAINING: A MATTER OF TIMING?

Patrice Brassard — 2008-01-28T00:00:00Z

In this manuscript, Loimaala et al.(1) have reported interesting findings regarding the impact of exercise training on indices of myocardial diastolic function in patients with type 2 diabetes. They observed the absence of significant change in myocardial tissue velocities in patients with uncomplicated type 2 diabetes following a one-year endurance and resistance exercise training program. The authors also noted significant improvements in maximal oxygen consumption (VO2max), muscle strength and glycemic control. One of the conclusions provided by the authors as regards to the absence of any influence of chronic exercise on diastolic function indices was that “a much longer non-pharmacological intervention (or aggressive medical therapy) is needed to obtain improvement in myocardial diastolic function”.

These results are of interest since we have recently reported that the normalization of diastolic dysfunction was possible in well-controlled, uncomplicated patients with type 2 diabetes after exercise training (2). Indeed, 45% of our patients with well-controlled type 2 diabetes and diastolic dysfunction who performed 3 months of endurance exercise at 60-70% of VO2max normalized their diastolic dysfunction. In comparison, no control subject with type 2 diabetes who did not perform aerobic exercise training normalized their diastolic dysfunction. In light of these conflicting conclusions, one may argue that the known duration of diabetes as well as the severity of diastolic dysfunction (abnormal relaxation pattern;pseudonormal pattern; restrictive pattern) will have an important influence on whether or not chronic exercise can reverse diastolic dysfunction, and not only the length of the exercise training program.

Potentially longer known duration of diabetes in the cohort of patients studied by Loimaala et al. compared to ours might partly explain why no beneficial impact of exercise training on myocardial diastolic function’s indices was observed. Indeed, their patients had to be diagnosed for three years or less at study enrolment. However, no details are provided about the mean disease duration in each group. In comparison, patients in our exercising group had known diabetes duration of 5+/-7 months. A period of less than three years since diagnosis might be perceived as a relatively short amount of time. However, one need to remember that any significant increase in the period since diagnosis will most likely have an impact on patients’ cardiac function. Indeed, the duration of diabetes is associated with the severity of cardiac dysfunction (3). Accordingly, one possibility could be that the diastolic function related abnormalities present in patients studied by Loimaala et al. were already too advanced to normalize in response to such a chronic exercise stimulus. The presence of hypertension in a majority of patients could also have had a noticeable contribution to the severity of diastolic dysfunction in their cohort.

However, it would have been interesting for Loimaala et al. to include detailed information about the severity of diastolic dysfunction as well as the number of patients with diastolic dysfunction. Smart et al.(4) have recently reported that a 16-week endurance and resistance exercise training program did not positively influence diastolic dysfunction in patients with heart failure, preserved ejection fraction and diastolic dysfunction. Interestingly, a majority of patients from this study had a pseudonormal pattern. In contrast, almost every patient who did normalize its diastolic dysfunction in our study had an abnormal relaxation pattern, therefore a less severe diastolic dysfunction. Accordingly, we might speculate that diabetics with less severe diastolic function impairments still have the possibility to normalize their diastolic dysfunction. However, as one of our patients with a pseudonormal pattern also reversed its diastolic dysfunction, our results also suggest that it may not be necessarily too late for a patient with a more severe diastolic dysfunction to normalize it in response to exercise training.

On the other hand, according to the available information in the manuscript regarding the severity of diastolic dysfunction, another possibility could be that a majority of patients with diabetes studied by Loimaala et al. who exercised had some alterations in diastolic function without overt diastolic dysfunction. One could thus also argue that a near normal diastolic function is difficult to normalize. Taken together, results provided by this study along with ours suggest that the timing for patients with type 2 diabetes to begin an exercise training program is crucial in order to reverse diastolic dysfunction. This being pointed out, I agree with Loimaala et al. that an exercise training program of longer duration might be needed to observe a positive, and probably a more important, influence of this therapeutic approach on diastolic impairments in patients with type 2 diabetes. Clearly, several issues regarding the normalization of diastolic function impairments in patients with type 2 diabetes request further research.

References

1.Loimaala A, Groundstroem K, Rinne M, Nenonen A, Huhtala H, Vuori I. Exercise training does not improve myocardial diastolic tissue velocities in Type 2 diabetes. Cardiovasc Ultrasound 2007; 5:32.

2.Brassard P, Legault S, Garneau C, Bogaty P, Dumesnil JG, Poirier P. Normalization of diastolic dysfunction in type 2 diabetics after exercise training. Med Sci Sports Exerc 2007; 39:1896-1901.

3.Raev DC. Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy? An echocardiographic study of young type I diabetic patients. Diabetes Care 1994; 17:633-639.

4.Smart N, Haluska B, Jeffriess L, Marwick TH. Exercise training in systolic and diastolic dysfunction: effects on cardiac function, functional capacity, and quality of life. Am Heart J 2007; 153:530-536.

Response to the comment by G. Thomas

Stephane Arques — 2007-04-10T00:00:00Z

First, I would like to thank Dr G. Thomas for its attractive comment on the current clinical applications of spectral tissue Doppler echocardiography for the diagnosis of heart failure with preserved left ventricular systolic function (HFPSF). I agree with Dr Thomas on the fact that this method is not “perfect” and that care should be taken before applying it, as reported in the review.

However, currently, what do we need in daily practice for the diagnosis of HFPSF?

We need a simple, reliable and reproducible marker of the severity of myocardial dysfunction for patients who present with symptoms compatible with the diagnosis of heart failure but without obvious left ventricular systolic dysfunction.

Undeniably, the E/E’ ratio fulfills all these criteria since it has been largely validated by numerous, well-recognized research teams not only for the diagnosis of elevated left ventricular filling pressures irrespective of left ventricular systolic function (see the review), but also for the diagnosis of the cardiac contribution to exercise intolerance and acute dyspnea (see the review) and for risk stratification in chronic congestive heart failure regardless of left ventricular ejection fraction [1-5]. Interestingly, most of these studies emphasize the usefulness of E/E’ beyond the analysis of mitral filling.

The “Holy Grail” quest for the “perfect” Doppler-derived marker of left ventricular filling pressures is not over, but currently, I simply recommend the use of spectral tissue Doppler echocardiography as a hallmark for the diagnosis of HFPSF in daily practice.

1.Acil T, Wichter T, Stypmann J, Janssen F, Paul M, Grude M, Schelde HH, Breithardt G, Bruch C: Prognostic value of tissue Doppler imaging in patients with chronic congestive heart failure. Int J Cardiol 2005; 103: 175-181.

2.Dokainish H, Zoghbi WA, Lakkis NM, Ambriz E, Patel R, Quinones MA, Nagueh SF: Incremental predictive power of B-type natriuretic peptide and tissue Doppler echocardiography in the prognosis of patients with congestive heart failure. J Am Coll Cardiol 2005; 45: 1223-1226.

3.Troughton RW, Prior DL, Frampton CL, Nash PJ, Pereira JJ, Martin M, Fogarty A, Morehead AJ, Starling RC, Young JB, Thomas JD, Lauer MS, Klein AL: Usefulness of tissue doppler and color M-mode indexes of left ventricular diastolic function in predicting outcomes in systolic left ventricular heart failure (from the ADEPT study). Am J Cardiol 2005; 96: 257-262.

4.Bruch C, Rothenburger M, Gotzmann M, Sindermann J, Scheld HH, Breithardt G, Wichter T: Risk stratification in chronic heart failure: independent and incremental prognostic value of echocardiography and brain natriuretic peptide and its N-terminal fragment. J Am Soc Echocardiogr 2006; 19: 522-528.

5.Fukuta H, Sane DC, Brucks S, Little WC: Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 2005; 112: 357-363.

Is E/E' really reliable?

George Thomas — 2007-04-10T00:00:00Z

I read with great interest the review article “Current clinical applications of spectral tissue Doppler echocardiography (E/E' ratio) as a noninvasive surrogate for left ventricular diastolic pressures in the diagnosis of heart failure with preserved left ventricular systolic function”. I congratulate the authors for their extensive review of literature on the subject.

They discuss the clinical application of the E/E’ ratio “which has been consistently found to be more reproducible in daily practice”. All the papers using spectral tissue Doppler for recording mitral annular velocities have “produced convincing evidence of a positive, linear relation of E/E’ with invasively determined mean LV diastolic pressure regardless of LV ejection fraction, rhythm and heart rate” using conventional statistical method of correlation. But is the data acquisition correct? If not, could these papers be the proof of an ad hoc hypothesis to demonstrate the validity of tissue Doppler?

There are philosophical, methodical and applicational flaws in tissue Doppler[1], so factoring this flawed value to the scientifically valid flow Doppler value would corrupt the latter. In which case, all the correlations produced could be “nonsense” or “spurious” correlations.

Even if we consider the tissue Doppler values as acceptable, what does E/E’ mean? It is the early mitral filling flow velocity divided by early mitral annular tissue relaxation velocity. So what is derived is early mitral flow velocity per unit of mitral annular tissue relaxation velocity. So far, so good. Does this automatically relate to higher left atrial pressures? It is common knowledge that flow Doppler patterns progress from “E/A normal” to “E/A reversal” with higher left atrial pressures. A higher E velocity in “E/A normal” and a lower E in “E/A reversal” goes against this assumption even after dividing with the usual E’ values.

The authors feel the combination of E’ with peak E velocity (i.e., E/E’ ratio) is assumed to “overcome the influence of ventricular relaxation on peak E velocity and reflect left atrial pressure.” The principle may be theoretically correct. It could remove the bias due to different relaxation values in different patients. But what about the application in the same patient? The different points around the mitral annulus ring give different tissue Doppler values. The E value being the same, you will get different E/E’ values. The article agrees to this by stating that “values of >10, >12 and >11 for lateral, septal, and average E/E’, respectively, can be proposed for predicting pulmonary capillary pressure >15 mmHg in the presence of preserved LV systolic function”. So to “overcome the influence of ventricular relaxation on the peak E velocity” multiple values of E’ need to be taken which would be tantamount to introducing a systematic error. Besides, such an exercise (determination of E/E’ ratio) goes against the scientific “principle of parsimony”.

The commonly interrogated medial mitral annulus on 2D apical 4-chamber image has an area of about 0.5 cm2 to 1.5 cm2. In this wide area, where exactly do you place the sample volume? This is considering the fact that the velocities change on minor changes in positioning. Similarly, the medial annulus is common to both the left and right ventricles. How much of an influence the right ventricle has needs to be addressed.

Once again congratulations to the authors for their exhaustive review of literature. In the case of trans-mitral flow Doppler analysis with its inherent complexities we do not need to factor in another variable like E’ and compound the problem. What is required is the application of the Occam’s Razor to derive some meaningful clinical information.[2]

References:

1.Thomas G. Tissue Doppler echocardiography – A case of right tool, wrong use

Cardiovascular Ultrasound 2004, 2:12

2.Thomas G. Classification of transmitral Doppler patterns. Indian Heart J. 2005;57(3):275-6.