title: Cardiac time intervals by tissue Doppler imaging M-mode echocardiography: reproducibility, reference values, association with clinical characteristics and prognostic implications.
abstract: BACKGROUND
  The preservation of normal cardiac time intervals is intimately related to normal cardiac physiology and function. In the ailing myocardium, the cardiac time intervals will change during disease progression. As left ventricular (LV) systolic function deteriorates, the time it takes for myocardial myocytes to achieve an LV pressure equal to that of aorta increases, resulting in a prolongation of the isovolumic contraction time (IVCT). Furthermore, the ability of myocardial myocytes to maintain the LV pressure decreases, resulting in reduction in the ejection time (ET). As LV diastolic function declines further, early diastolic relaxation proceeds more slowly, explaining the prolongation of isovolumic relaxation time (IVRT). Consequently, the IVRT/ET and the myocardial performance index (MPI), defined as (IVCT + IVRT)/ET, will detect cardiac dysfunction with an increase, irrespective of whether the LV is suffering from impaired systolic or diastolic function. A novel method of evaluating the cardiac time intervals has recently evolved. Using tissue Doppler imaging (TDI) M-mode through the mitral valve (MV) to estimate the cardiac time intervals may be an improved method reflecting global cardiac time intervals and eliminating beat-to-beat variation and regional differences. However, little is known about the usability of the cardiac time intervals obtained by this novel method.
  
  
  OBJECTIVE
  To compare the reproducibility, association with clinical characteristics, association with established echocardiographic and invasive measures of systolic and diastolic function, and the usefulness in predicting all-cause mortality in the general population, for the MPI obtained by the conventional method (MPIConv) and by the novel method of obtaining the MPI (MPITDI). Furthermore, to define normal values of the cardiac time intervals obtained by TDI M-mode through the MV. In addition, to investigate if the cardiac time intervals are able to identify miniscule cardiac impairments in individuals with hypertension, which are unrecognized by conventional echocardiography. Lastly, to evaluate the prognostic value of the cardiac time intervals and the combined indexes of systolic and diastolic performance, IVRT/ET and MPI, obtained by TDI M-mode method in low risk participants from the general population and in highrisk patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI).
  
  
  METHODS
  The research involved three prospective observational studies. Within the Copenhagen City Heart Study, a large community based study of cardiovascular risk factors, the cardiac time intervals were obtained by TDI M-mode in 1,915 participants. Additionally, in the present thesis the cardiac time intervals were also obtained in 391 patients who were admitted with a STEMI and treated with pPCI at Gentofte Hospital. All patients were examined by echocardiography median two days (IQR 1-3) after the STEMI. Lastly, we also included a population (n = 44) of patients who underwent left heart ventricular catheterization and had the MPITDI and MPIConv measured. In all cohorts baseline data and an assessment of cardiac function were obtained by conventional echocardiography. Follow-up data on admission were obtained from the Danish National Board of Health's National Patient Registry and from the national Danish Causes of Death Registry.
  
  
  RESULTS
  MPITDI had superior reproducibility, was less confounded by association with clinical characteristics, and provided superior prognostic information in a low-risk population as compared to MPIConv. Additionally, the MPITDI (but not MPIConv) was significantly associated with most invasive and established echocardiographic measures of systolic and diastolic function. The cardiac time intervals displayed a significant dose-response relationship, with increasing severity of elevated blood pressure and increasing left ventricular mass index. They identified impaired cardiac function in participants with hypertension, not only independent of conventional risk factors, but also in participants with a normal conventional echocardiographic examination. The combined cardiac time intervals which include information on both the systolic and diastolic function in one index (IVRT/ET and MPI) provided independent prognostic information, regardless of rhythm, incremental to conventional and novel echocardiographic parameters of systolic and diastolic function both in the general population and in patients with STEMI treated with pPCI.
  
  
  CONCLUSIONS
  The novel TDI M-mode method is superior to the conventional method of obtaining the MPI, both when comparing reproducibility, validity, prognostic power and the ability to display both the systolic and diastolic function in one index. The cardiac time intervals obtained by TDI M-mode reveal impaired cardiac function in persons with hypertension even when conventional echocardiography gives the impression of normal cardiac function. The combined cardiac time intervals which include information on both the systolic and diastolic function in one index (IVRT/ET and MPI) provide prognostic information incremental to conventional and novel echocardiographic parameters of systolic and diastolic function both in the  general population and in  patients with STEMI treated with pPCI.
authors.affiliation: tor.biering@gmail.com.
authors.forename: Tor
authors.initials: T
authors.lastname: Biering-Sørensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000503:physiopathology; D004452:Echocardiography; D015150:Echocardiography, Doppler / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D016277:Ventricular Function, Left / Q000502:physiology*; D055815:Young Adult