unveiled and new pharmacological approaches are designed and implemented in the setting of diastolic dysfunction and HFNEF. As for the adrenergic system, many other neurohumoral mechanisms commonly associated with the progression of heart failure syndrome have been described to acutely and positively modify cardiac function. In regard to myocardial diastolic properties, AngII and ET-1 ﬁgure as two unquestionable new paradigms of such modulation (schematically depicted in Fig. 1). Being mostly regarded as positive inotropic and vasoconstrictor mechanisms in acute heart failure but decompensatory ones in the chronic heart failure setting, their ability to acutely modify diastolicfunction has been widely dismissed. This gap has been ﬁlled by our recent observations that AngII and ET-1 can signiﬁcantly improve diastolicfunction by means of increasing relaxation velocity and decreasing myocardial stiffness in a time- frame that is too short to alter the ECM. In the clinical ground, these effects may translate into an enhanced capacity for the ventricle to increase its end-diastolic volume at concurrently lower ﬁlling pressures. In the acute heart failure setting and upon neurohumoral activation, ventricular wall stress decreases and the odds of congestion are signiﬁcantly attenuated. The same effects are ascribed to NO and, more recently, to U-II (see Table 1 for an overview). Though, the net effect in the human myocardium integrating the actions of all these peptides should always be regarded as a complex and still incompletely under- stood issue that also depends on the integrity of the endothe- lium, probably leading to different diastolic cardiac behaviors in the healthy state and in the diseased heart. An observation that further underscores the importance of diastolicfunction modulation in cardiovascular homeostasis is the redundancy of effects among neurohumoral mediators that activate different intracellular signaling pathways. Multiple signaling mediators seem to converge on a similar effect in the regulation of myoﬁlamentary calcium sensitivity and myocardial distensibil- ity. Either through direct or indirect stimulation of PKA (adrenalin), PKC (AngII and ET-1) and/or PKG (NO and U-II), these mediators share the acutely-decreasing effect of myocar- dial stiffness, highlighting the existence of several ways to achieve a common end: an enhanced diastolicfunction.
Data management and analysis were performed using SYSTAT 12.0 (SYSTAT Software, Inc., USA). Summary data are reported as means±SD, unless otherwise specified. Linear regression was used to predict distance walked during the 6MWT and MLWHFQ scores. Independent variables included in the univariate model were gender, age, body surface area, left chamber dimensions, and LV systolic and diastolicfunction indexes. Significant associations indicated by simple linear regres- sion were included in the multivariate linear regression. Colinearity was avoided by removing from the model those variables with a significant correlation coefficient and selecting those with the greatest clinical relevance. Pearson’s correlation was used to analyze the association between LV systolic function indexes and E/e’. The level of significance was set at P,0.05.
known that diastolicfunction influences exercise capacity (26-28). However, whereas in the sham group, variations in the e9 index were associated with an increase of only 5.38 meters in walked distance, in the CPAP group, each increment in the e9 index was associated with a mean increase of 16.05 meters in walked distance. This result indicated an interaction between e9 index variation and CPAP for the improvement of functional capacity. Therefore, in a general sense, although acute CPAP therapy did not affect ventricular function, it may cause an incremental increase in functional capacity in those patients who respond to acute CPAP with improved diastolicfunction. Our results also indicate that the effect of CPAP may involve factors other than ventricular function, includ- ing, for instance, pulmonary gas exchange, which was not analyzed in this study.
myoﬁlament Ca 2+ sensibility (Wendt and Stephenson 1983), shifts the transition to a decompensatory response towards smaller afterload levels. On the other hand, b-adrenergic stimulation, which enhances SERCA2a activity and decreases myoﬁlament Ca 2+ sensibility, thereby shifts the transition to a decompensatory re- sponse toward higher afterload levels. Diastolic distur- bances induced by afterload are therefore attenuated. These results are highly suggestive of a relation between SERCA2a activity and the occurrence of afterload- induced disturbances of relaxation and diastolicfunction. Additionally, it was also documented that afterload- induced diastolic disturbances are related not only with relaxation rate but also with the available time to relax (Leite-Moreira and Correia-Pinto 2001). The time available to relax is altered by heart rate, which is sig- niﬁcantly higher in rats. Taking into account these molecular and heart rate diﬀerences between rabbits and rats, it would be interesting to investigate how rats handle all these factors without compromising normal cardiac diastolic physiology.
Diastolicfunction was evaluated with the following parameters: 1 - early ventricular filling (E wave) and late ven- tricular filling (A wave) and by the E/A wave ratio, whose normality criterion, for practical purposes, was considered ≥1.0; 2 - measurement of the isovolumetric relaxation time (normal IRT - <110 msec); 3 - atrial deceleration time (normal ADT - <240 msec).
Results: TIMI frame counts of left anterior descending artery, circumlex and right coronary artery were signii- cantly higher in CSF group (p<0.01). There were signii- cant decrease in early and late diastolic maximum illing rates (E/A) (p<0.01), and signiicant prolongation at early deceleration time (p<0.01) on conventional echocar- diography in CSF group. The tissue Doppler parameters which have been measured from the four region of mitral annulus were as follows: the mean Em velocity and mean Em/Am ratio were signiicantly lower in CSF patients (p<0.01), and mean Am velocity were signiicantly higher (p<0.01). E/Em, a non-invasive predictor of left ventricular illing pressures, is similar in both groups.
No study assessing the fetal diastolicfunction through the unidimensional left atrial profile was found. Studies assessing dias- tolic function in fetuses of diabetic mothers are scarce. We spe- culate that the assessment of left atrial shortening may represent an alternative for evaluating diastolicfunction in fetuses of diabetic mothers. Therefore, this study aimed at testing the hypothesis that left atrial shortening may be lower in fetuses of diabetic mothers than in healthy fetuses of nondiabetic mothers.
The LV diastolic dysfunction is very much prevalent in the general population. It is a significant prognostic indicator of several heart diseases, including AMI. Diastolic dysfunction is the incapacity of the ventricle to accept blood flow or to do so without a compensatory increase in the left atrial pressure. The physiologic influences on these measurements are varied and must always be considered. TSANG et al. , in 2002, found a positive correlation among LAV, age, cardiovascular risk score and final LV diastolic and systolic sizes. From this work, the LAV has been utilized as an adjuvant measurement in the analysis of the diastolicfunction. PRICHETT et al. , in 2003, suggested that the LAV reflected the atrial transformation associated with cardiovascular disease.
The main finding of this study is the significant enhancement of LA passive function, as noticed by the increment of LA passive emptying and reduction of LA active function after 24 weeks of CPAP treatment. This finding seems to be directly associated with the improvement of LV diastolicfunction after the effective treatment of OSA. To the best of our knowledge, this is the first study which analyses the effects of CPAP on the LA dynamics and LV diastolicfunction using RT3DE and tissue Doppler technologies. In addition, the randomised placebo- controlled intervention group with similar demographic vari- ables, supports the idea that OSA contributes significantly to left atrial dysfunction
The prospective study was performed between January 2007 and February 2008 in Erciyes Univercity Medical Faculty Hospital. Study population consisted of 42 patients with ESRD. Before an AVF was surgically created for HD, the patients were evaluated by conventional and Doppler echocardiography. Then, an AVF was surgically created in the patients, who started HD via AVF when the AVF was compleated. After the first HD session (mean 76.14 ¡ 11.37 days) the second echocardiographic evaluations were performed. The patients were dialyzed via AVF three times a week for four hours. The second evaluations were performed 6-8 hours after the last HD session to avoid from acute volume loading. LV systolic and diastolicfunction parameters were obtained. The local ethics com- mittee approved the study, and informed consent was obtained for each patient.
Left ventricular systolic and diastolicfunction was evaluated at rest and at the intensity corresponding to the anaerobic threshold in the sitting position, with the chest inclined at about 35 degrees and with the collimator positioned at a left anterior oblique projection. Image acquisition was performed after in vivo red cell labeling with Tc-99m pertechnetate, using a Siemens Or- biter camera with a ZLC-DIGITRAC 75 de- tector (Siemens, Hoffman Estates, IL, USA). Images were photographed with a Micro Dot Imager (Siemens) and recorded in a Microdelta computer (Siemens). Left ven- tricular ejection fraction was calculated as left ventricular end-diastolic counts minus left ventricular end-systolic counts, divided by end-diastolic counts, always subtracting periventricular radiation. Peak filling rate was calculated by a series of subtractions of each successive frame in the part of the left ventricular function curve corresponding to the rapid filling period, and identified as the peak rate of filling normalized by the end-
was greater in SLE due to this increase in ventricular rigidity, disrupting ventricular illing. Besides, the end-diastolic volume was also increased in this disorder, indicating the involvement of the myocardium in SLE. All those factors predispose the worsening in diastolicfunction, leading to an increase in LV diastolic volume and illing pressures. Thus, this early altera- tion in ventricular volumes maybe the precursor of the process of ventricular dysfunction.
Doppler echocardiography became a fundamental tool in the evaluation of the diastolicfunction and of ventricular filling pressure . The physiology of the diastole and diastolic dysfunction are seen in respect to different aspects. These are the cellular aspect (metabolic including relaxing), mechanical aspect (cavitary represented by the distensiblity or complacency) and clinical aspect (expressed by the signs and symptoms) can be studied and interpreted from the excellent synoptic state (Figure 1), proposed by OMMEN & NISHIMURA .
Added diagnostic value of a combined approach Numerous noninvasive estimates of diastolicfunction and left ventricular filling pressures have been extensively investigated in the past decades including particularly Doppler- echocardiographic indices. However, many of them failed to yield a robust criterion for DD as a single parameter, why a comprehensive assessment of various indices and different algorithms have been proposed [1,2,48,49]. The latter analysis evaluated several echocardiographic measurements of diastolicfunction and the corresponding diagnostic performance at different cut-off values. While all measurements showed decent values for sensitivity and specificity, the indexed left atrial volume ≥ 34ml/min - being an independent predictor of atrial fibrillation, ischemic stroke, heart failure and death - turned out to be specific albeit less sensitive than other parameters [1,49,50]. In conclusion, a combination of lateral E/e’ ratio, indexed left atrial volume and the difference between duration of reverse pulmonary vein atrial systolic flow and duration of mitral valve atrial wave flow showed a considerable added diagnostic value with sensitivity and specificity values, which were similar to those in the strategy proposed by Paulus et al. , yet much higher than the one described by Nagueh et al. . However, similar to other parameters, pulmonary vein flow measurements are known to be achievable only in a modest portion of all patients, thus depicting the limited applicability of certain Doppler-echocardiographic measurements . While the latter confirms our experience, it has to be emphasized that the ECG parameters assessed in our analysis could be obtained in every individual. Furthermore, our combined strategy particularly including the novel index and the indexed left atrial volume yielded a substantial added diagnostic value for the recognition of DD, challenging the above-mentioned studies.
4. Dincer I, Kumbasar D, Nergisoglu G, Atmaca Y, Kutlay S, Akyurek O ¨ , et al. Assessment of left ventricular diastolicfunction with Doppler tissue imaging: effects of preload and place of measurements. Int J Cardiovasc Imaging. 2002;18:155–60, doi: 10.1023/A:1014697208218. 5. Foley RN, Parfrey PS, Kent GM, Harnett JD, Murray DC, Barre PE. Serial change in echocardiographic parameters and cardiac failure in end-stage renal disease. J Am Soc Nephrol. 2000;11:912–6.
In the general population, there has been interest in the association between the Glu298Asp polymorphism within endothelial nitric oxide synthase (eNOS) and heart failure [6, 7]. Al- though this polymorphism has been associated with endothelial dysfunction and progression of CKD through nitric oxide effects , it is not known if this polymorphism is associated with early cardiac structural changes that occur in non-dialysis CKD. In light of this, we investigated if this gene variant is associated with changes in systolic and diastolicfunction, based on de- tailed cardiac magnetic resonance imaging (CMR) in non-dialysis CKD patients with no known history of heart failure.
Several pathophysiological mechanisms may be involved in LV dilation and dysfunction during diabetes . Im- paired myocardial contractility is an important cause of cardiac dilation and dysfunction . In fact we found that myocardial systolic function, evaluated in isolated papillary muscle preparations, was depressed in diabetic rats, which presented increased time to peak tension and decreased + dT/dt. Contractile reserve was also impaired in SHR-DM as developed tension, unchanged at basal condition, was reduced after positive inotropic stimulation with post-rest contraction, increased extracellular Ca 2+ concentration, and isoproterenol added to nutrient solution. Myocardial diastolicfunction was unchanged. Isolated papillary muscle preparations allow us to properly control preload and afterload and thus analyze intrinsic myocardial function.
Study limitations - This study, similarly to others previously published, has several practical limitations. Among them: 1) considering that patients with left ventricular asynergy were left out, it is possible that patients with kinesis abnormalities (for instance, those affecting the basal segment of the interventricular septum) may present abnormalities in the profi les of the variables analyzed, which does not express the overall behavior of the ventricle, which may be normal for the behavior of its diastolicfunction parameter 16 ; 2) we have
E/(E’×S’) was the best predictor of LV end-diastolic pressure in a heterogeneous population of cardiac patients, and more closely related to LV filling pressure compared to E/E’, E’, S’ or E. In terms of new-onset AF, E/(E’×S’) was the only independent predictor in the multivariate analysis in this study. This novel parameter associates an index of diastolicfunction (E/E’) and a marker that explores LV systolic performance (S’) and therefore may provide supplementary information compared to each component considered separately. The superiority of E/(E’×S’) over the combined index of Hirata can be attributed to the capacity of reduced S’ to identify LV dysfunction in individuals with normal LVEF 28 . TDI does not require tracing of endocardial