Assessing cardiac preload and fluid responsiveness accurately is important when attempting to avoid unnecessary volume replacement in the critically ill patient, which is associated with increased morbidity and mortality. The present clinical trial was designed to compare the reliability of continuous right ventricular end-diastolic volume (CEDV) index assessment based on rapid response thermistor technique, cardiac filling pressures , and transesophageal echocardiographically derived evaluation of left ventricular end-diastolic area (LVEDA) index in predicting the hemodynamic response to volume replacement.We studied 21 patients undergoing elective coronary artery bypass grafting. After induction of anesthesia, hemodynamic parameters were measured simultaneously before (T1) and 12 min after volume replacement (T2) by infusion of 6% hydroxyethyl starch 200/0.5 (7 ml/kg) at a rate of 1 ml/kg per min.TD) was 10% or greater in 19 patients and under 10% in two. There was a significant correlation between changes in CEDV index and changes in SVITD , but there were no significant correlations between changes in CVP, PCWP and LVEDA index, and changes in SVITD. The only variable apparently indicating fluid responsiveness was LVEDA index, the baseline value of which was weakly correlated with percentage change in SVITD .The volume-induced increase in thermodilution-derived stroke volume index (SVITD following fluid administration was better predicted by LVEDA index than by CEDV index, CVP, or PCWP.An increased cardiac preload is more reliably reflected by CEDV index than by CVP, PCWP, or LVEDA index in this setting of preoperative cardiac surgery, but CEDV index did not reflect fluid responsiveness. The response of SVI Accurate evaluation of cardiac performance and preload status, and assessment of fluid responsiveness are important goals in the treatment of critically ill patients. Despite the current controversy surrounding the usefulness of and risks associated with the pulmonary artery catheter (PAC) ,2, the PSeveral studies have emphasized the good correlation between estimates of right ventricular end-diastolic volume (RVEDV) by thermodilution-derived right ventricular ejection fraction (RVEF) and surrogates of stroke volume -20. HoweA recently available Swan–Ganz catheter with a rapid response thermistor permits nearly continuous assessment of cardiac output (CO), RVEF and RVEDV, which should be more applicable in the ICU. The measurement variability associated with the intermittent bolus technique is eliminated by this catheter, and continuously assessed RVEDV (CEDV) should be more accurate than RVEDV based on intermittent thermodilution; therefore, CEDV may be a valuable marker of cardiac preload and a predictor of fluid responsiveness.The purpose of the present study was to compare the accuracy of CEDV derived using a new right-heart ejection fraction catheter and commonly used preload parameters  in predicting the response of stroke volume to volume replacement in mechanically ventilated cardiac surgical patients.After obtaining approval from the local ethics committee and written informed consent from all participants, we studied 21 patients  undergoing elective coronary artery bypass grafting. Patients with valvular heart disease, intracardiac shunts, regional myocardial asynchrony, peripheral vascular disease, preoperative dysrhythmias, and an ejection fraction under 30 % were excluded from the study. Dynamic variables, such as pulse pressure variation, were not measured to assess fluid responsiveness in our investigation.All patients received an arterial catheter for continuous monitoring of arterial blood pressure . Anesthesia was induced with fentanyl (5 μg/kg) followed by etomidate until loss of consciousness and pancuronium (100 μg/kg), and maintained using 1.5% sevoflurane end-expiratory, supplemented with bolus doses of fentanyl (up to 20 μg/kg) and pancuronium (50 μg/kg) for neuromuscular blockade. Mechanical ventilation (without positive end-expiratory pressure) at a constant tidal volume of 7 ml/kg to an end-tidal partial carbon dioxide tension of 30–35 mmHg was maintained at a inspired fractional oxygen of 0.5 throughout the study.TD).After induction of anesthesia, a 7.5 Fr right-heart ejection fraction catheter  was inserted via an 8.5 Fr introducer into the right internal jugular vein and connected to a Vigilance Monitor system (Edwards Lifesciences) for continuous assessment of CO (CCO), CEDV and of RVEF, and for determination of CO using the intermittent thermodilution technique  was positioned to obtain a transgastric midpapillary short-axis view of the left ventricle. This position was maintained over the whole period of data acquisition. Echocardiographic images and electrocardiograms were recorded together, and end-diastole was defined as the greatest left ventricular cross-sectional area immediately after the R-wave peak on the electrocardiogram.Correspondingly, end-systole was defined as the smallest left ventricular dimension during the last half of the T wave. An independent reviewer, who was blinded to the condition of the trial participants, analyzed TEE images. LVEDA and left ventricular end-systolic area were traced edge to edge, including the papillary muscles. Fractional area change was calculated as (LVEDA – left ventricular end-systolic area)/LVEDA. Three measurements, performed at end-expiration, were analyzed and averaged.TD) was 10% or greater, or as nonresponders if the increase in SVITD was under 10%.All hemodynamic parameters were measured simultaneously after induction of anesthesia, when CCO had stabilized (T1). A second measurement was performed (T2) 12 min after volume replacement by infusion of 6% hydroxyethyl starch 200/0.5 (7 ml/kg) at a rate of 1 ml/kg per min (mean 579 ml). Measurements were taken in a hemodynamically steady state, in the absence of vasoactive drugs. Patients were classified as responders to volume loading if the increase in thermodilution-derived stroke volume index  values of variables that reflect preload  and the change in SVITD . P < 0.05 was considered statistically significant.For statistical analysis, all volume variables were indexed to body surface area. Statistical analysis was performed using the SPSS 12.0 software . After assessment of normal distribution using the Lilliefors modification to the Kolmogorov–Smirnov test, the Student's t-test was used to compare variables. Because the thermodilution technique still represents the 'gold standard' for assessment of cardiac index (CI), we conducted linear regression analyses between changes in variables that reflect preload  and changes in the preload-dependent variable SVIDemographic data for the patients included in the present study are summarized in Table TD was 10% or greater (range 21.8–93.4%) in 19 patients (responders) and under 10% in two patients (nonresponders).Except for HR, all hemodynamic parameters changed significantly after volume replacement Table . The volTD revealed a significant correlation , but linear regression analysis between changes in CVP, PCWP and LVEDA index, and ΔSVITD did not identify any significant correlations among variables. LVEDA index at baseline and the percentage ΔSVITD were weakly correlated , but linear regression analysis between the remaining variables reflecting preload  did not reveal any significant relationships  and ΔSVI2 was associated with lack of response but that RVEDV index below 90 ml/m2 was associated with a high rate of response to fluid administration [2 and a lack of response in some patients with an RVEDV index below 90 ml/m2. Furthermore, the response to volume loading was rather unpredictable when RVEDV index ranged between these extremes. Based on those findings, no threshold value may be proposed to discriminate between responders and nonresponders before fluid application [Over recent years numerous studies have been performed to evaluate the usefulness of thermodilution-derived estimates of RVEDV index in a variety of clinical situations -20,25-28stration . In contstration  reportedlication ,21. Nevelication ,27,29 anlication ,18.TD, whereas there was a lack of correlations between changes in the remaining preload-indicating variables and ΔSVITD, suggesting that increased cardiac preload is more reliably reflected by CEDV index than by CVP, PCWP, or LVEDA index. Some investigators questioned the clinical significance of correlation between RVEDV index and continuously assessed CI, but Durham [In the present study ΔCEDV index was significantly correlated with ΔSVIt Durham  and Nelst Durham  and theiSeveral authors described RVEDV index as a marker of cardiac preload, indicated by the linear correlation between CI and RVEDV index -20. AlthIt should be noted that the terms 'cardiac preload' and 'fluid responsiveness' are not exchangeable. The increase in SVI depends on ventricular function; a decrease in ventricular contractility decreases the slope of the relationship between end-diastolic volume and stroke volume  and move2 = 0.19; P < 0.01) between the response to fluid challenge and baseline RVEDV index in 41 critically ill patients. Wagner and Leatherman [2 = 0.19; P < 0.05), but they stated that RVEDV index was not a reliable predictor of response to fluid.For this reason, the more relevant question concerns the value of RVEDV index as an indicator of fluid responsiveness, but until now only limited and inconsistent information has been available regarding the value of this variable ,22. A vaTD  nor a very low (<90 ml/m2) CEDV index proved to be a reliable predictor of hemodynamic response to volume challenge. In accordance with Wagner et al [In the present study, baseline values of CEDV index were not correlated with changes in SVITD Fig. . Furtherer et al , even onA factor that could possibly affect the accuracy of CEDV index is the presence of a low RVEF , becauseTD following fluid loading  declare that they have no competing interests.CW designed the study, processed the data, and wrote the manuscript. CF collected the clinical data. AK collected the clinical data and participated in the study design. SL collected the clinical data. CP designed the study and collected the clinical data. CK performed the statistical analysis and extensively revised the manuscript. All authors read and approved the final manuscript.


Hypertension is a global problem and it is prevalent in Nigeria. Left ventricular hypertrophy is a major complication of hypertension with risk of sudden death and arrhythmias among others. Abnormal left ventricular geometric patterns also increase the burden of morbidity and mortality. It is therefore important to know the different left ventricular geometric patterns in Nigerian hypertensives because of their prognostic significance.One hundred (100) newly presenting hypertensives  and 100 controls  were recruited for the study. All were subjected to clinical evaluation and full echocardiographic examination was performed according to the ASE recommendation. The relative wall thickness and the presence or absence of echocardiographic left ventricular hypertrophy were used to determine the various geometric patterns2 = 74.30, p value < 0.0001).The mean age of the hypertensive subjects was 56.06 (± 7.68) years while that of the control subjects was 56.10 (± 7.68) years. There was no significant difference in the mean ages of the two groups. In the hypertensive subjects 28% had normal geometry, 26% had concentric remodeling, 28% had concentric hypertrophy and 18% had eccentric hypertrophy. In the control group, 86% had normal geometry, 11% had concentric remodeling, 3% had eccentric hypertrophy and none had concentric hypertrophy. There was statistical significance when the geometric patterns of the hypertensive and controls were compared (χThe study showed that only 28% of the hypertensive subjects had normal LV geometric pattern while 86% of the normal subjects had normal geometry. There is need for longitudinal studies in order to prognosticate the various geometric patterns. Hypertension is a leading non-communicable disease in Nigeria. It has for long been globally recognised as the most prevalent cardiovascular disease. Increased left ventricular (LV) mass is a recognised complication of systemic hypertension and has been shown to be an important predictor of cardiovascular morbidity and mortality in hypertensives,2. SeverStudies had documented significant racial differences in the hypertensive heart,10. HoweOne hundred (100) consecutive, newly presenting adult hypertensive subjects aged 18 and above with blood pressure greater or equal to 140/90 mmHg seen at the cardiac clinic of University College Hospital, Ibadan were enrolled over 6 month period. Normal controls were recruited from among hospital staff, and relatives of hospital patients. Ethical approval was obtained from the institutional ethical review board and informed consent was obtained from the study participants. Subjects with diabetes mellitus, chronic renal failure, valvular heart disease and previous myocardial infarction were excluded from the study.Blood pressure was measured with a mercury sphygmomanometer (Accosson) according to standard guidelines. SystoliThe study was powered at 90% to detect a 17% difference in the prevalence of LVH between hypertensive subjects and controls at a minimum sample size of 89 subjects.Echocardiographic examinations were done with the patient in partial left lateral decubitus position using an Aloka SSD 1700 machine  with 3.5 MHz transducer. Two-dimensional guided M-mode measurements were obtained as recommended by the American Society of Echocardiography . Two expLeft ventricular mass (LVM) was calculated using the formula that hasLV mass (g) = 0.8 (1.04 (IVSd + LVIDd + PWTd) 3 - LVIDd3) + 0.62.7 . Relative wall thickness (RWT) was calculated as 2 × PWTd/LVIDd. Increased relative wall thickness was present when RWT ≥ 0.45 [Left ventricular mass was indexed by the allometric power of height. Left veT ≥ 0.45 . LV geomNormal geometry – Normal LVMI and RWTConcentric remodeling-Normal LVMI and Increased RWTEccentric LVH – Increased LVMI and RWT < 0.45Concentric LVH – Increased LVMI and RWT ≥ 0.45LV ejection fraction (EF) was calculated using Teichholz's formula.Statistical analysis was performed with SPSS software version 10.0 . Data was expressed as the mean ± SD for continuous variables while frequencies are expressed as percentages. Categorical variables were compared with chi-square while means were compared with "t" test for independent samples. Differences among more than two groups were tested by one way analysis of variance (ANOVA) followed by the Scheffe's post hoc test. Significant P value was taken to be <0.05.One hundred hypertensive subjects  and 100 controls  aged 35 to 68 years participated in the study. The clinical characteristics of the subjects are as shown in Table 2.7 were also significantly more in the hypertensives. The LV geometric patterns of the hypertensive subjects were significantly different from that of the controls.Table 2.7 . Table Age did not correlate significantly with the relative wall thicknesses and the left ventricular mass indexed for height2.7 were significantly different among the various geometric patterns. Septal and posterior wall thicknesses were significantly larger in concentric hypertrophy when compared with other geometric patterns.Table Adaptation of the left ventricle to systemic hypertension is complex and it is characterized by functional and structural changes in the left ventricle. The old concept that the heart responds to systemic hypertension by developing concentric or eccentric hypertrophy have been challenged by recent studies,6,20. HySome authors,25 have Left ventricular adaptation to hypertension can present with any of the geometric patterns. The hemodynamic predominance between pressure and volume overload plays an important role in the determination and development of various LV geometric patterns. ConcentIt is quite significant that seventy-two percent 72%) of our hypertensive subjects had altered geometric patterns. Koren et. al.  in a 10 2% of ourLeft ventricular hypertrophy is associated with adverse heart consequences, including reduction in systolic and diastolic function, reducedSince relative wall thickness and left ventricular mass indexation derived from echocardiographic measurements are necessary in determining left ventricular geometric pattern, echocardiographic evaluation of the newly diagnosed hypertensive should be an essential step in their initial workup. In view of the abnormal geometric alterations in newly diagnosed hypertensives noted in this study, longitudinal studies to determine the prognosis of abnormal LV geometry in indigenous Africans are necessary.The study, though hospital based , showed that majority of the newly presenting hypertensives (72%) had abnormal LV geometric patterns. This may argue for the performance of echocardiography in all hypertensive subjects in order to determine the LV geometric pattern. Longitudinal studies of prognosis of abnormal LV geometry are needed to fully evaluate its natural course in indigenous Africans.The author(s) declare that they have no competing interests.AA conceived of the study and participated in the study design and drafted the manuscript, AAA participated in the study design and statistical analysis, OOO took part in the study design and study conception, AD contributed to the study design and statistical analysis, OSO participated in the study design and data acquisition, DBO participated in the study design and data acquisition, AOF conceived of the study and participated in the study design. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Right Ventricular Apical permanent pacing could have negative hemodynamic effects. A physiologic pacing modality should preserve a correct atrio-ventricular and interventricular synchronization. This can be obtained through biventricular pacing, left ventricular pacing, or from alternative right ventricular pacing sites.Direct His Bundle Pacing (DHBP) was documented as reliable and effective for preventing the desynchronization and negative effects of right ventricular apical pacing.  It is, however, a complex method that requires longer average implant times, cannot be carried out on all patients and presents high pacing thresholds. On the contrary, the parahisian pacing, with simpler feasibility and reliability criteria, seems to guarantee an early invasion of the His-Purkinje conduction system, with a physiological ventricular activation, very similar to the one that can be obtained with direct His bundle pacing.We present our experience on 68 patients who underwent a permanent right ventricular pacing in hisian/parahisian region, for advanced AV block and narrow QRS.  In the first 17 patients we performed a double-blind randomized controlled study, with two 6-months cross-over periods in parahisian and apical pacing, documenting a significant improvement of NYHA class, exercise tolerance, quality of life score, mitral and tricuspidal regurgitation degree, and interventricular mechanical delay. In the  subsequent 51 patients, in a mean follow of 21 months/patient,  the pacing threshold remained stable . The ejection fraction maintained medium-long term stable values, confirming the fact that the parahisian pacing can prevent deterioration of the left ventricular function.Parahisian pacing, therefore, has proven to be a reliable method, easy to apply and effective in preventing the negative effects induced by non-physiological right ventricular apical pacing. Right Ventricular Apical (RVA) stimulation has given clinical benefits and has resulted in a considerable improvement in the symptoms and life expectancy of millions of patients suffering from chronic or paroxysmal disorder of the cardiac electric excito-conduction (atrio-ventricular blocks and/or sinus node disease).In any case,  similar to the negative hemodynamic and clinical effects tied to the presence of spontaneous left bundle branch block, new data has emerged that show the presence of a left bundle branch type of activation induced by RVA pacing can have negative effects -5.- electric and mechanical left ventricular asynchrony;- negative remodeling of the left ventricular chamber;- alterations of the myocardial histopathology;- systolic and diastolic left ventricular dysfunction;- heart failure;- regional myocardial and kinetic perfusion defect;- functional mitral regurgitation;- left atrial dilation;- increased risk of atrial fibrillation;- induction of spontaneous ventricular arrhythmias;- hyperactivation of the sympathetic nervous system.The negative effects of RVA pacing can be summed up as follows:      During the isovolumetric contraction phase induced by the right pacing, there is notable variability in the changes in the muscular fiber lengths, with a rapid shortening  of the fibers near the pacing site, and a marked pulling of the fibers in the more remote regions. As a consequence, the energy generated by the premature activated fibers are dissipated by the internal resistance offered by the fibers not yet activated, causing regional differences in the mechanical work carried out . The finThe asymmetry of the left ventricular contraction induced by RVA pacing also causes an abrupt change in the temporal sequence of activation of the papillary muscles supporting the mitralic valve apparatus, with loss of coaptation of the valvular leaflets: that determines mitralic regurgitation (MR) and can favour atrial fibrillation and cardiac failure ,9.Several recent studies have showed the negative clinical consequences caused by RVA pacing:   CTOPP , Danish Based on the results of various clinical studies it is therefore clear that a physiologic pacing modality should preserve a correct atrio-ventricular activation and maintain or re-establish a correct ventricular synchronization.The most simple solution to avoid right ventricular pacing is to implant an AAI pacemaker in patients with intact atrio-ventricular and intraventricular conduction.  This solution, however, has always been scarcely applied because of the unjustified fear of a late atrio-ventricular block. An alternative solution is to implant a dual chamber device with an atrial and a ventricular lead, and to use dedicated algorithms that limit as much as possible the RVA pacing .When, however, ventricular pacing is necessary in a permanent way or for long periods of time, physiologic sites of pacing should be applied in order to prevent ventricular desynchronization .This can be obtained through biventricular pacing, left ventricular pacing or pacing from alternative sites of the right ventricle.In addition to the important randomized trials regarding the evaluation of cardiac resynchronization therapy  has been studied by various authors . RecentlA further evolution of RVOT pacing is the contemporaneous bifocal pacing of the apex and RVOT ; even inDirect His Bundle Pacing (DHBP) was described for the first time in 1967 by Scherlag , with anIn 2000, Deshmukh  presenteIn 2004, the same author  presente- the morphology and the duration of the native QRS and the paced QRS must be identical on the 12 standard ECG derivations ;- the HV interval on the original rhythm and the spike-QRS distance in the paced signal must be equal (with a tolerance margin of 10 ms) ;- the pacing threshold must be high (> 2V), since it must capture a specific non-muscular conduction tissue;- the pacing lead should be positioned with the distal pole (screw in) at the same level as one of the two electrodes of a mapping catheter on the His bundle (x-ray in both right and left anterior oblique projections) .This paper has allowed up to better clear up the questions relative to the pacing site; the parameters that allow for the direct pacing of the His bundle were defined :      -Other authors have also assessed the feasibility and effectiveness of permanent hisian pacing. Recently, Zanon  publisheThese studies have shown how the permanent pacing of the His bundle is a reliable and effective method for preventing the desynchronization and negative effects of RVA pacing.  It remains, however, a complex method that requires longer average implant times, cannot be carried out on all patients and presents high pacing thresholds.  There is also the theoretical risk of His bundle damaging and blocking, induced by the trauma and injury caused by the catheter screw-in lead.The parahisian pacing, with simpler feasibility and reliability criteria seems to guarantee, however, an early invasion of the His-Purkinje conduction system with a physiological ventricular activation, very similar to the one that can be obtained with direct His bundle pacing  Figure .Recently, Laske  assessedVictor  has rece- the distal pole of the catheter (screw-in) must be positioned as much as possible next to the mapping dipole of the electrophysiological catheter of reference (within 1 cm in the right and left oblique projections) ;- the duration of the paced QRS can be larger than the spontaneous QRS, but the duration must be at least 50 ms shorter than the QRS obtained with the RVA pacing and, in any case, not more than 120-130 ms ;- the electrical axis of the paced QRS must be concordant with the electrical axis of the spontaneous QRS;- the interval between the spike and start of paced QRS is less than the HV time of the original rhythm;- the pacing threshold must be less than 1 V, since the muscular portion of the interventricular septum is paced.The correct criteria for the realization of parahisian pacing could be :      -From September 2000, to December 2006, at the Cardiology Clinic of the Hospital in Novara , 68 patients underwent permanent right ventricular pacing in hisian/parahisian region.- indication for ablation of the AV node for chronic atrial fibrillation with high ventricular rate, not controlled by pharmacological therapy ,- concomitant structural cardiopathy;- narrow spontaneous QRS complexes, even during the tachyarrhythmia phases, documented with Holter recording.From September 2000 to June 2003, the first 17 patients were enrolled  . Inclusion criteria were:      - NYHA functional class;- quality of life (QoL), through the "Minnesota Living with Heart Failure" questionnaire ;- 6-minute walking test;- 24 hour Holter monitoring;- standard complete echocardiogram with measuring of the left ventricular EF, the left ventricular telediastolic and telesystolic volumes, the degree of mitral and tricuspid regurgitation , the systolic pulmonary pressure through the tricuspid regurgitation speed with continuous doppler;- the interventricular mechanical delay measuring the left and right ventricular pre-ejection times (from the start of the QRS and the start of the aortic and pulmonary flow detected with pulsed Doppler).Before the procedure, all the patients underwent a clinical and hemodynamic evaluation through:      After radiofrequency ablation of the atrioventricular node, an active fixation bipolar lead was placed as close as possible to the hisian dipole of a quadripolar catheter mapping the His bundle.  The position of this catheter was considered correct for hisian/parahisian pacing if the duration of the QRS was the same as the spontaneous QRS (DHBP) or ≤ 130ms and with concordant axis with respect to the original QRS (parahisian pacing).  A second conventional bipolar lead was placed on the tip of the right ventricle. The septal and the apical catheters were then connected respectively to the "atrial" and "ventricular" channel of a pacemaker, programmed in "DDDR" modality  with "short" atrio-ventricular delay (90 ms), so that: if the hisian/parahisian pacing  was effective, the next apical ventricular pacing ("ventricular" channel) was inhibited or in any case fell in the refractory period; on the contrary, if the hisian/parahisian pacing was ineffective, the ventricular pacing was guaranteed by the conventional back up apical pacing.After the institutional ethics committee approval and written informed consent, these patients were subject to a double-blind randomized controlled study in two 6-month periods: a) with RVA pacing; b) with hisian/parahisian pacing. At  the end of each period a total re-evaluation was made through the same evaluations carried out before enrolling:  NYHA functional class, quality of life, 6-minute walking test, echocardiogram and Holter ECG.After enrolling the first 17 patients, the method was considered reliable; we considered it safe enough to position only the catheter in the parahisian region without a back-up apical catheter. Indication for implant was extended also to patients in sinus rhythm with AV conduction disorders, using an atrial lead together with the parahisian lead, both connected to a dual-chamber DDDR pacemaker.From July 2003 to December 2006, parahisian pacing was carried out: a) in another 35 patients with chronic atrial fibrillation and indication for atrio-ventricular node ablation; b) in 16 patients in sinus rhythm with 1°-2° or 3° degree atrio-ventricular block, all with narrow QRS complexes (< 120ms). The first follow up was carried out after 3 months and then every six months, re-evaluating both pacing, hemodynamic and functional parameters.A case history, therefore, of 68 patients  was put together. In 38 patients, in order to obtain the hisian/parahisian pacing, a bipolar catheter with 1.5mm retractable screw lead  was used.  In 5 patients, a bipolar catheter with 3 mm retractable screw lead was used in controlled clinical evaluation . In the last 2 years, in 25 patients a bipolar, fixed screw, steroid eluting lead was used .  Only in 3 patients (4%), excluded from the case history, reliable positioning of the parahisian pacing was not possible, due to catheter instability .The radiological exposure time referred to only the pacing system implant was  15 ± 8.8 minutes . Electric measuring from the parahisian site was carried out in bipolar configuration.The pacing threshold from the hisian site varied from 3.8 V in case of direct hisian pacing (obtained in 14/68 patients: 21%), to values of always < 1 V in case of parahisian pacing   (in 54/68 patients: 79%). The average parahisian pacing threshold was  0.6 ± 0.3 V (0.5 ms); pacing impedance 841 ± 114 ΩΩ, endocavitary potential 7.7 ± 4.8 mV; high "far-field" type atrial potentials were never recorded by the parahisian catheter.The average duration of the basal QRS was 91.2±13.5 ms, of QRS by parahisian pacing 123.1±13.9 ms; while the QRS obtained by apical pacing had an average duration of  164.5±18 ms .As recently published by our group in JACC , in the Significant improvement of the NYHA functional class was obtained with the parahisian pacing, with improvement in exercise tolerance, quality of life score, mitral and tricuspid regurgitation degree .A significant relationship was observed between the pacing site and the degree of mechanical desynchronization: conventional apical pacing showed an interventricular mechanical delay  (47 ± 19 ms), higher than during parahisian pacing (34 ± 18 ms), p < 0.05.The left ventricular EF did not show any significant differences, with a slight improvement in the case of parahisian pacing  (53 ± 8%) if compared to apical pacing (50 ± 8%). Nonetheless, left ventricular volumes were greater in patients with EF <  52% , with respect to patients with EF > 52% . Moreover, a site-specific interaction between the group of patients with EF < and > than 52% was observed (p=0.076): in patients with lower EF, there was a reduction in the left ventricular volume of 13 ± 20% with parahisian pacing and  5 ± 21% with apical pacing; in patients with higher EF there was an increase in the ventricular volume of  26 ± 66% with parahisian pacing and 35 ± 58% with apical pacing.The average follow up of our patients is currently 21 months/patient, ranging from 70 months for the first patient enrolled to 2 months for the last patient.The parahisian pacing lead slightly moved 3 cm from its original parahisian position in only one patient, maintaining, however, a paced QRS superimposable to the post-implant QRS. In one patient, with a DHBP, the catheter in the hisian site was deactivated at 31 month of follow up because of an increase in the pacing threshold  . In one patient affected by valvular cardiopathy with EF 35%,  who had already undergone upgrading from apical pacing to parahisian pacing,  an ICD was implanted following an episode of fainting with Holter documentation of sustained ventricular tachycardia: parahisian pacing was maintained.In the medium-long term follow-up, patients with parahisian pacing showed the same QRS duration as the value recorded at the implant. The pacing threshold in parahisian region did not have any significant variations, with values that remained with acceptable safety margins  .The prolonged parahisian pacing led to an improvement in the NYHA functional class and the quality of life .  ExerciThe EF maintained medium-long term values (51 ± 10%) superimposable to enrollment values  (51 ± 11%) (p=0.5), confirming the fact that the parahisian pacing can prevent deterioration of the left ventricular function, that can, on the other hand, be accelerated by the RVA pacing. Mitral regurgitation  and tricuspid regurgitation  showed improvement after parahisian pacing, with values that reach statistic significance only for the mitral insufficiency .The main purpose of permanent cardiac electrostimulation  is to maintain an adequate cardiac rhythm, trying to restore the physiology of the normal excito-conductive physiology of the heart as much as possible. Up until now,  importance had been given to two elements that were considered fundamental for physiological pacing: maintenance of the atrioventricular sequence and the rate-responsive function. Pacemakers, therefore, were considered "physiological".Conventional RVA pacing induces, however, a desynchronization between right and left ventricles. The problem can clinically be of little importance in the presence of a structurally normal heart.  In case of manifest or latent left ventricular dysfunction, this anomalous contraction sequence can condition negative remodeling, worsen the left ventricular function and induce or aggravate heart failure.- maintain the correct stimulation-contraction sequence between atria and ventricles;-contraction sequence between atria and ventricles;- favour the increase of the cardiac frequency according to the metabolic needs;- maintain the synchrony between right and left ventricle. Truly physiological pacing, therefore, must:      In case of spontaneous electromechanical desynchronization with left bundle block, the biventricular pacing has widely shown to be effective in improving the cardiac function and the quality of life of the patients.In presence of an atrioventricular block, but with electric intraventricular conduction preserved, pacing must be as physiological as possible. Even if the biventricular pacing guarantees these physiological characteristics, His bundle pacing can be an effective alternative, using the His-Purkinje system to maintain the intraventricular conduction activated in a preferential way.Direct His bundle pacing is, however, a complex method, that required longer implant times: it is characterized by high pacing thresholds and presents the theoretical risk of a His bundle block, induced by the trauma and by the lesion caused by the catheter screw.Our experience has led us to believe that parahisian pacing can be obtained in a simpler and reliable way:  in this case, the high muscular part of the intraventricular septum is activated, while at the same time the hisian conduction axis is penetrated.  As proof of this fact,  the QRS remains rather narrow (120-130 ms) and with electric axis concordant with the non-paced spontaneous QRS.The improvement in the functional and hemodynamic parameters that can be obtained with the parahisian pacing with respect to  conventional right apical pacing in patients affected by chronic atrial fibrillation and who have undergone ablation of the AV node, has been shown by our experience.  These results seem to be modulated by the left ventricular function. When the patients were stratified according to the ejection fraction (EF > 52% versus EF < 52%), various changes in the left ventricular volumes were observed.  When the pump function was depressed, physiological parahisian pacing guaranteed the best results with a more evident reduction of left ventricular telediastolic and telesystolic volumes; when, on the other hand, left ventricular function was normal, volumetric differences obtained with the two types of pacing were less evident. In addition, the degree of mitral and tricuspid regurgitation improved significantly only with the parahisian pacing, thus suggesting that the clinical and hemodynamic improvements obtained with this pacing site are probably mediated by the improvement of the interventricular desynchronization, that was further shown by the reduction in the interventricular mechanical delay, associated with the narrowing of the QRS.The long-term follow-up results of patients with parahisian pacing confirm a stable improvement of the functional class and quality of life with respect to the same at enrollment,  and of exercise tolerance too. These results show how functional data continues to improve, maintaining clinical stability during long-term follow-up. In spite of a natural progression of the underlying cardiopathy, these benefits are due to the maintaining of a synchronous activation sequence between the two ventricles, in addition to the correction of the underlying arrhythmia obtained by the pacing (correct atrioventricular activation sequence and regularization of the cardiac frequency). Even the ejection fraction maintains good values, and the degree of mitral and tricuspid regurgitation continues to improve.Parahisian pacing, therefore, has proven to be a reliable method, easy to apply and effective in preventing the negative effects induced by non-physiological right ventricular apical pacing. The use of this method of physiological pacing as first choice in patients with initial left ventricular dysfunction, preserved intraventricular conduction and the need for a high percentage of ventricular pacing is, therefore, justified.


Junctional ectopic tachycardia (JET) is a rare type of supraventricular arrhythmia. Even if its management has improved in recent years, it remains a great challenge for the cardiologist. Two are the possible clinical presentations of this arrhythmia: as a primary idiopathic disorder during infancy, configuring the so called "congenital" JET, or more often as a transient phenomenon immediately after surgery for congenital heart disease, giving rise to the "post-operative" variety.The congenital form, firstly described as a distinct entity by Coumel et al. in 1976 [Congenital JET is hampered by high mortality. Secondary dilated cardiomyopathy, ventricular fibrillation and sudden cardiac death have also been reported ,3.Clinical presentation of congenital JET usually ranges from birth to 4 weeks of age. Sporadic cases of history of intrauterine tachycardia, with sometimes hydrops fetalis, have been reported in patients who at birth showed overt JET ,4,5.Usually, high percentage of patients present, at the time of referring, echocardiographyc evidences of impaired left ventricle function and clinical signs of congestive heart failure. However, it has been noted that age of tachycardia presentation is not related to the occurrence of congestive heart failure or impaired left ventricular function. On the contrary, clinical status seems related to the ventricular rate at presentation .The incidence of congenital heart disease in presence of congenital junctional ectopic tachycardia has been reported sporadic .The diagnosis of junctional ectopic tachycardia usually is based on electrocardiographic evidence of a narrow complex tachycardia (heart rate ranging from 160 bpm to 300 bpm) and atrio-ventricular dissociation.  SometimePrenatal diagnosis of JET has been also reported, with the superior vena cava/ascending aorta Doppler echocardiography approach . DopplerElectrophysiological mechanism of JET is thought to be abnormal automaticity within the His bundle . JET typTachycardia is not inducible by programmed stimulation in baseline status, but can be elicited after sympathetic stimulation with isoproterenol. Programmed atrial and ventricular stimulation usually are not able to terminate tachycardia, that can be only transiently suppressed by atrial and/or ventricular pacing, exhibiting a resetting curve-response to extrastimuli during tachycardia.JET can coexist with the occurrence of other types of arrhythmias. Scheinman et al.  reportedEven more interest is attributed to this arrhythmia by the fact that it is a familiar condition. In a multicenter study, Villain reports a familiar history of JET positive in 50% of the children. . In our Congenital JET is hampered by high mortality, with up to 34% mortality rate. The exact mechanism related to death in congenital JET is still unclear. Most are sudden death, that has been found also in children with "well compensated" tachycardia .Sporadic case of sudden death has been attributed to a dramatic evolution to paroxysmal complete AV block . Probably, the dramatic clinical course of these patients is the extreme expression of the pathological process occurring in the His bundle region, causing JET in a first time and finally the complete loss of AV conduction.Necropsy reports underlined the importance of His-bundle fibbers severe disruption ,12 or foHenneveld reported a case of an 8 months old girl affected by a rapid ventricular rate JET, who developed two years later a complete heart block with rapidly increasing left ventricular end diastolic diameter . The patIn other cases it can not be excluded that a pharmacological treatment can be responsible of the depression of ventricular excitability, leading to a slow unsatisfactory ventricular escape rhythm in case of AV block and sudden cardiac death. However, in some cases it can not be excluded the potential proarrhythmic effect of the drugs used to control the arrhythmia . In our Treatment is indicated in infants with symptoms, reduced ventricular function or rapid rates '17. The The pharmacological treatment of JET is hampered by a high rate of failures. Several drugs have been tested, but a comprehensive analysis of efficacy has not been performed yet.The largest study available is a multicenter study performed in nineties by European and American teams who reviewed dates of 26 pts treated with digoxin, propranolol and/or amiodarone [Digoxin did not affect ventricular rate in any patients and has been demonstrated to be not completely safe in patients with congenital JET. Sporadic cases have been reported in which patients affected by congenital JET and severe cardiac failure developed ventricular fibrillation or faster tachycardia (up to 400 beats/min) during progressive digoxin loading .Amiodarone seems to have the highest response rates: it has been shown to be effective alone in decreasing the ventricular rate to less than 150 beats/min in a percentage between 50-70% of the cases ,6.Sporadic reports of medical treatment efficacy exist also about Propafenone ,18, FlecOther studies have also tested phenytoin, which was able to control ventricular rate but caused ataxia, ajmaline, which intravenous infusion was followed by ventricular tachycardia and verapamil which caused cardiovascular collapse .Personal experience has shown that in those cases not responding to a single drug regimen, as association of antiarrhythmic agents with different electrophysiological effects (Amiodarone + a Ic antiarrhythmic drug) may control otherwise untreatable congenital JET. Otherwise the association Propafenone or Flecainide plus Amiodarone could reduce the Amiodarone dose keeping an high efficacy of the pharmacological therapy .Recently Dorman et al. have described a protective effect of magnesium supplementation on JET in paediatric patients undergoing surgery for congenital heart defects . This coAll pharmacological therapies are burdened by a high risk of toxicity as they have to be maintained at high dosage for long time in young patients.Congestive heart failure is a frequent complication of JET with high ventricular rate and its management is even more difficult. In these cases it has been underlined the negative inotropic effects of antiarrhythmic drugs and the limitations in the use of sympathomimetic agents. Isoproterenol, dopamine, dobutamine and amrinone all increase the JET rate. Sodium Nitroprusside has to be avoided too, since low blood pressure will reflexly increase adrenergic tone.A definitive treatment could be the removal of the arrhythmogenic area. Surgical His ablation has been attempted in some critical patients, with contrasting results . In one Very controversial is still the matter of prophylactic pacemaker implant to prevent sudden death. In the multicenter study  most parWalsh suggested to evaluate AV conduction with transesophageal electrophysiological test in all patients with congenital JET and consider pacemaker insertion only if impaired conduction can be demonstrated by atrial stimulation, or by the observation of spontaneous AV block on ECG and Holter monitoring .Since JET therapy relay on different medical options, a staged treatment protocol is advisable: a pharmacological approach should be tested and carried on, also with a multi drug treatment, while catheter ablation can be a definitive option in critically ill patients, when drugs fail or when tachycardia becomes chronic and the patient is dependent on a potentially toxic therapy.


Congestive heart failure (CHF) is a common, debilitating and usually lethal condition responsible for enormous burden on health care. The recent trials have shown improvement in morbidity and mortality with ACE inhibitors and beta blockers ,3. HowevIn 1990, Hochleitner et al  reportedThe reasons for the discrepancies in the results of these studies is possibly due to the detrimental effect of pacing induced broadening of the QRS complex duration in severe ventricular disease resulting from Right Ventricular (RV) apical pacing offsetting the beneficial effect of increased ventricular filling time. As a result the focus has now shifted to Left Ventriuclar (LV) or biventricular (BiV) as opposed to RV pacing supplemented with the lessons learnt from the optimization of the AV delay.The association of asynchronous ventricular contraction with ventricular dysfunction has been recognized for many years. In recent years the presence of left bundle branch block (LBBB) has been shown to correlate with decreased LV function, reduced peak dp/dt. LBBB results in asynchronous ventricular contraction with the LV lateral wall contracting much later that the inverventricular septum in addition there is an RV-LV asynchrony with RV contracting earlier than LV.The presence of conduction disturbances is seen in 20-30% of the patients with congestive heart failure and contributes to the worsening of symptoms due to improper co-ordination of LV contraction.CRT aims at 3 different levels (a) AV level (b) intraventricular level (c) interventricular level. At present this is achieved by pacing or sensing the right atrium, pacing the right ventricle (near the interventricular septum) and pacing the left ventricle (using the coronary venous branches), also called biventricular pacing.The present LV leads have lower profile with preformed curves. Most of the leads followed the same conventional central-stylet technology, with curves being fashioned to negotiate the variabilities in cardiac vein anatomy.  Recently over-the-wire lead deployment systems have been developed  and have the procedure like an angioplasty. Overall, the success rate for implantation of left-sided leads ranges from 75 to 93%.The implantation of biventricular pacing is more technically challenging than a dual chamber pacing for the reason of placing the LV pacing lead appropriately. Prior to the introduction of the endocardial LV pacing leads, surgical implantation of these leads epicardially was the norm.It is now possible to pace by entering the cardiac veins which are approached through the coronary sinus and obtain a reasonable threshold in one of the cardiac veins. The presence number, location, size and tortousity of posterior and lateral branches is usually variable. The coronary veins are thus studied by contrast injections with a balloon inflated catheter within the coronary sinus and subsequently the lead can be placed precisely. The posterolateral veins yield the best haemodynamic outcome and are the ones targeted for the placement of LV leads.The findings from the PATH - CHF trial  suggest The primary variable has been the QRS duration - an electrial marker for spatially dispersed mechanical activation . A QRS dSeveral studies have studied the effects of BiV pacing on the acute haemodynamics. It has been seen that BiV pacing improves cardiac output and enhances ventricular systolic function as assessed by maximal rate of pressure rise and pressure volume loops. Furthermore this improvement in LV systolic function occurs while concomitantly reducing myocardial oxygen consumption.Three placebo control studies have been completed - the PATH - CHF trial , the MUSThe recently published MUSTIC study  used a cThe recently completed MIRACLE trial  is the lClearly, there are major important questions about whether there is a sustained benefit on morbidity and reduced hospitalization and whether there is a favorable effect on overall and cardiac mortality. In this regard, it is important that the ongoing trails such as COMPANION, which are addressing these key questions, proceed to completion so that the role of this therapy can be properly and fully evaluated. The mortality impact of resynchronization may ultimately be tied in with ICDs, particularly if the results of ongoing multicenter trials show survival benefits from such devices in HF.Another question relates to the prospective identification of responders. New methods examining regional wall motion hold promise for generating a dyssynchrony index that could improve on current, more indirect methods. The optimal method of therapy itself is unresolved. As noted, questions remain as to whether BiV stimulation is needed, whether multisite left-heart stimulation would enhance the efficacy, or, if an RV lead is to be placed, where the optimal location is and what the best timing delay is between RV and LV stimulation.A large unresolved question is whether this therapy is going to be useful in patients with atrial fibrillation. Some studies have suggested utility, although larger trial data remain inconclusive. Unlike the sinus rhythm patients, in which there is some degree of freedom in the AV delay to optimally time a resynchronization effect, the AV node in atrial fibrillation patients is generally ablated, and then patients are treated using a BiV pacing mode. This involves regularization of the heart rate with rate-responsive generators, as well as activation of both lower chambers. Rate response serves to simulate normal effects of autonomic tone, but it is not a perfect replacement for physiologic control. Furthermore, in patients without an existing conduction delay, BiV pacing may not yield as good a response as that with His-Purkinje conduction. More studies are clearly needed in these patients.Finally, the existing evidence indicating deterioration of systolic function and energetic efficiently with pacing-induced dyssynchrony suggests that standard RV apex pacing in individuals with cardiac failure may not be the ideal approach. In patients with cardiodepression but a narrow QRS complex and normal intraventricular conduction who need pacing for rate control, a BiV system may prove superior, but this clearly needs to be tested.


Left ventricular (LV) diastolic dysfunction (DD) and diastolic heart failure (HF), that is symptomatic DD, are due to alterations of myocardial diastolic properties. These alterations involve relaxation and/or filling and/or distensibility. Arterial hypertension associated to LV concentric remodelling is the main determinant of DD but several other cardiac diseases, including myocardial ischemia, and extra-cardiac pathologies involving the heart are other possible causes. In the majority of the studies, isolated diastolic HF has been made equal to HF with preserved systolic function  but the true definition of this condition needs a quantitative estimation of LV diastolic properties. According to the position of the European Society of Cardiology and subsequent research refinements the use of Doppler echocardiography  and the new ultrasound tools has to be encouraged for diagnosis of DD. In relation to uncertain definitions, both prevalence and prognosis of diastolic heart failure are very variable. Despite an apparent lower death rate in comparison with LV systolic HF, long-term follow-up (more than 5 years) show similar mortality between the two kinds of HF. Recent studies performed by Doppler diastolic indexes have identified the prognostic power of both transmitral E/A ratio < 1  and > 1.5 (restrictive patterns). The therapy of LV DD and HF is not well established but ACE-inhibitors, angiotensin inhibitors, aldosterone antagonists and β-blockers show potential beneficial effect on diastolic properties. Several trials, completed or ongoing, have been planned to treat DD and diastolic HF. Heart failure (HF) is a clinical syndrome whose symptoms and signs are due to increased extravascular water and decreased tissue / organ perfusion. The definition of the mechanisms inducing HF needs the measurement of both left ventricular (LV) systolic and diastolic function since HF may occur in patients with either normal or abnormal LV ejection fraction (EF) .per se main determinants of symptoms and signs of HF. Several other cardiac pathologies as well as extra-cardiac diseases involving secondarily the left ventricle can also affect myocardial diastolic properties and determine LV DD.Arterial hypertension is the most common risk factor for HF in the general population and myocardial infarction, LV hypertrophy (LVH) and valve heart disease represent predictors of subsequent HF in hypertensive patients of both genders . The proLV DD and diastolic HF, that is the symptomatic DD, represent clinical entities which can be described at different levels, from the hystologic and ultrastructural features to the clinic manifestations and diagnostic instrumental findings, until the prognostic and therapeutic aspects. The growing interest for DD and for diastolic HF has been developed gradually in the last 10–15 years. It rises mainly from the advancement of non invasive imaging tools, above all Doppler echocardiography, which, to date, allows easy and repeatable identification of LV diastolic abnormalities, and by the growing impulse of pharmaceutical industry, at constant search of new therapeutic applications. In relation to the increase of the average life and the future projections which suggest HF as the most important pathology of the new millennium, particularly in the elderly population, it has to be understood how diagnosis, prognosis and therapeutic management of DD represent very attractive perspectives.Although in normal hearts the transition from contraction to relaxation begins much more before LV end-systole, i.e., at 16% to 20% of the ejection period ,9 and evIn merely descriptive terms, diastole can be divided in 4 phases :Isovolumetric relaxation, period occurring between the end of LV systolic ejection  and the opening of the mitral valve, when LV pressure keeps going its rapid fall while LV volume remains constant. This period Is mainly attributed to the active LV relaxation, with a lower, variable contribution of elastic recoil of the contracted fibers;1. LV rapid filling, which begins when LV pressure falls below left atrial pressure and the mitral valve opens. During this period the blood has an acceleration which achieves a maximal velocity, direct related to the magnitude of atrio-ventricular pressure, and stops when this gradient ends. This period represents a complex interaction between LV suction (= active relaxation) and visco-elastic properties of the myocardium (= compliance);2. diastasis, when left atrial and LV pressures are almost equal and LV filling is essentially maintained by the flow coming from pulmonary veins – with left atrium representing a passive conduit – with an amount depending of LV pressure, function of LV "compliance".3. atrial systole, which corresponds to left atrial contraction and ends at the mitral valve closure. This period is mainly influenced by LV compliance, but depends also by the pericardial resistance, by the atrial force and by the atrio-ventricular synchronicity .4. Cardiac catheterization allows to assess the pressure-volume relation along the overall cardiac cycle. Among the various hemodynamic measurements, τ (= time constant of the isovolumic-pressure decline) and DP/DV ratio, expression of LV end-diastolic myocardial stiffness, are the main invasive measurements of LV diastolic function . On the The extracellular matrix (ECM), corresponding to fibrillar collagen, is an important structure for processes of both myocardial contraction and relaxation. It facilities the arrangement of the cardiomyocites into the most suitable allocation for the development of force and shortening, giving a substantial support to the maintenance of an effective myocardial performance . The myoIn the clinical setting the coexistence of systolic and diastolic dysfunction in patients with symptomatic HF occurs very often. In fact, LV stiffness (or compliance) is related to the length of myocardial fibers, reflecting in its turn on LV end-diastolic dimensions. LV diastolic function, through the influence on left atrial and capillary wedge pressures, determines the onset of symptom in patients with prevalent LV systolic dysfunction too.systolic dysfunction and/or systolic heart failure. In the second one, LV structural abnormalities (= LV concentric geometry) induce functional alterations of DD. When diastolic dysfunction becomes symptomatic – that is, when dyspnoea occurs – diastolic heart failure rises.In parallel to the ultra-structural level, the clinical progression of HF may follow two different routes. In the first one, as it happens after acute myocardial infarction, post-infarction LV dilation (= remodelling) leads to The majority of patients affected by isolated diastolic HF show symptoms not at rest but in relation to stress conditions (II NYHA class). Symptoms can be induced or worsened by, firstly, physical exercise but also by events as anaemia, fever, tachycardia and some systemic pathologies. In particular, tachycardia reduces the time needed for global LV filling, thus inducing an increase of left atrial pressure and consequent appearance of dyspnoea, because of accumulation of pulmonary extravascular water.primum movens of DD. Alone or, better, combined together, these tools permits to recognize normal diastole as well as to diagnose and follow the progression of DD from the pattern of abnormal relaxation (grade I of DD) until pseudonormal (grade II) and restrictive (grade III-IV) patterns  is detectable before the appearance of the abnormalities involving LV transmitral inflow and is uniform in non hypertrophic patients while it becomes prominent at the septum in presence of overt LVH [It is controversial whether LV DD is necessarily accompanied on the development of LVH or rises up independent of it -7,40-43.vert LVH . Table 2vert LVH . This covert LVH .heart failure with preserved systolic function or, better, with normal EF, has been made equal to isolated diastolic heart failure. A truly correct definition of this clinical entity should, however, be done on the grounds of direct estimation of LV diastolic function and establishment of reference normal values. Strong controversy has been developed in the previous years about this issue, with opposite scientific positions. The American point of view, corresponding to the Framingham Heart Study investigators, has sustained the concept that diastolic HF is "definite" only when an invasive hemodynamic assessment shows diastolic alterations in the temporal proximity of the acute episode [The evidence of acute HF in absence of overt LV systolic dysfunction rises by the experience of Gandhi and coworkers : thirty- episode . On the  episode  , provided of vasodilation activity, could be particularly indicated for the management of DD. A recent study has tested the ability of nebivolol on 26 patients affected by HF and normal EF, in comparison with the traditional atenolol, combining both invasive hemodynamic and Doppler echocardiographic assessment . After sOn these grounds, pharmaceutical industry has planned clinical trias to evaluate the prognostic impact of several drugs on diastolic HF. Indeed, the trials completed to date have been disappointing. The CHARM-2   did not New therapeutic fields for HF will be opened in view of the associations observed between the state of coronary microcirculation and LV diastolic function . The benDD and diastolic HF are common entities in the clinical practice, particularly in hypertensive population. The diagnosis of diastolic HF can be considered in the presence of the signs of HF and normal EF (50% or more) but it should be usually supported by a Doppler examination. Diastolic HF is associated to four-fold increase mortality. If it is true that the mortality expectation is lower than in patients with systolic HF, it is even true that this difference has a trend to be blunted during long-term follow-up, with possible overlapping after 5.5 years or more. The therapeutic management of diastolic HF is, at least partially, empirical and several studies, ongoing or completed, have been planned to test the effects of ACE-inhibitors, angiotensin-inhibitors and β-blockers. The prevention of diastolic HF may be obtained by a better control of blood pressure values and of concomitant risk factors in hypertensive patients.None.None.


As a matter of public utility, the guidelines in the diagnosis and treatment of such patients will have to be cheap, available, easily reproducible, and ideally will furnish answers for the clinician questions not in a binary "black or white" manner, but with graduations, so if possible it has to be quantitative. The present paper aim to focus on the current clinical applications of tissue Doppler and of left atrial function and remodeling, and its pathophysiologic relationship with the left ventricle, as will be cleared in the documented review of echocardiography that follows, considering that the need of universal data on the syndrome of the failing heart does not mean, unfortunately, that all patients and clinicians in developing countries have at their own health facilities the same imaging tools, since they are, as a general rule, expensive.Multiparametric echocardiographic imaging of the failing heart is now increasingly used and useful in decision making in heart failure. The reasons for this, relies on the need of different strategies of handling these patients, as differentiation of systolic or diastolic dysfunction, as well as on the gamma of approaches available, such as percutaneous and surgical revascularization, devices implantations, and valvular regurgitations and stenosis corrections. Congestive heart failure in patients with normal left ventricular diameters or preserved left ventricular ejection fraction had been pointed out recently as present in a proportion so high as 40 to 50 percent of cases of heart failure, mainly due to the epidemics in well developed countries, as is the problem of not well controlled metabolic states (such as obesity and diabetes), but also due to the  Heart failure is considered a world endemic problem and data ratified by The European Society of Cardiology (ESC), according to recent publications, estimates a prevalence of symptomatic manifestations in the general European population ranging from 0.4 to 2% . In otheSociedade Brasileira de Cardiologia [American College of Cardiology/American Heart Association [Under the physiopathologic point of view, CF is characterized as myocardial function failure. Without neglecting the autonomous nervous system hormonal mechanisms or the other adapting or deleterious bimolecular implications, the most relevant aspect is that, in this case, the cardiac structure does not provide contraction and ejection with sufficient systolic volume, and does not promote the adequate diastolic arrangements or both situations are not processed appropriately. And this heart dysfunction is closely associated with the heart geometric structural alterations. According to this statement, the aggregation of CF diagnostic stratification is mentioned, not only based on clinical symptom classes but also associated with structural dysfunction stages  proposed by the diologia  and the ociation  the guidociation . A direcociation ,7. Recenociation . TherefoThe LV diastolic function can be measured by estimate or index direct measurement through various cardiovascular imaging methods: radioisotopic ventriculography, heart catheterization, and magnetic resonance imaging, however, the echocardiographic-Doppler study is the most applied tool, due to its high feasibility of transmitral Doppler indices, almost universal availability and low cost .Since 1980, the pulsed Doppler technique for the left ventricular analysis allows the diastole study in a noninvasive form, initially in animals then in human beings . The infPseudonormal pattern: it presents an E/A > 1 ratio as the normal pattern; however, it reflects a velocity increase of the E-wave flow secondary to the pressure elevation in the left atrium, a relaxation deficit and an initial decrease of the LV compliance. The IVTR is diminished due to the higher initial transmitral gradient. The pulmonary venous flow presents abnormal D velocity predominance as this one relates with the increase of the early mitral flow (E-wave). This situation represents an ischemia dysfunction progression, hypertensive or LV overload eventually becoming difficult to differentiate in relation to the real normal pattern; (c) restrictive pattern: the velocity of the early diastolic filling is increased which results in E/A ratio > 2 and in an IVTR and EDT decrease. In this case, the rapid blood flow to the less complacent ventricle results in a rapid elevation of the LV filling pressure, supplanting the atrial pressure which could also cause ventricle-atrial regurgitation in the diastolic phase. As it was observed in the previous pattern, there is here a pulmonary venous flow diastolic increase which corresponds to the transmitral E-wave elevation. The AR and the AR-dur are increased and they keep a positive correlation with the LV final diastolic pressure. The restrictive pattern is related to advanced stages of heart failure and with the worst clinical prognosis  recognizing normal and alternate diastole patterns. According to the technical point of view, the TD analyzes the blood flow by measuring the high frequency signals and the low amplitude of the blood cells . The metpseudonormalization or even a restrictive pattern type; the heart rate elevation leads to the velocity alterations and often to the spectral Doppler wave fusion with a consequent loss of the qualification analysis of the ratio between the waves. Meanwhile, the LV preload variable status can also set alterations inversely proportional in the TMD indices. It is reasonable, however, that this method is complemented with others for a comprehensive ventricular filling function analysis [The TMD index contribution to the CF diagnostic and prognostic measurement is undeniable -15, evenanalysis .The tissue pulsed Doppler (TPD) consists of a modality linked with the echocardiography by Doppler which allows the estimate of the myocardial displacement velocity during the cardiac cycle analysing signals of low frequency and high amplitude produced by the myocardial tissue .The myocardial velocity phenomenon can be analyzed by three models: bidimensional coded by color, unidimensional coded by color, and the more commonly used, the pulsed spectral mode, with which the systolic myocardial displacement S', and the E' and A' waves can be respectively registered Figures  and 3.The tissue Doppler E' velocity index is primarily influenced by left atrial pressure, left ventricle relaxation and left ventricle systolic pressure in order of decreasing significance , and forpseudonormalized patterns [The TMD index susceptibility, in relation to the LV preload variations, represents this method main disadvantage for the diastolic analysis in a global manner. The TPD indices contribute to a less susceptible measurement to the preload variation. In a recent study performed by our research group, we have observed that in the hypertensive diastolic measurement, there was not significant variation of E' index with the bedside noninvasive maneuvers that induces the preload elevation , while the TMD index E has varied significantly (E = 68.9 ± 11.9 cm/s × E = 75.8 ± 15.7 cm/s), Figure . This prpatterns ,20.pseudonormalized was observed after the infusion of 500 to 700 ml of saline physiological solution (0.9% NaCl concentration), but the TPD diastolic pattern analysis did not show any significant alteration .In the invasive study model, Sohn et al , alreadyTau index (time constant isovolumic relaxation), considered the gold-standard for LV myocardial relaxation, according to Sohn et al. [Tau  in 38 volunteers with relaxation abnormalities. Recently, an important study has been published by Nagueh et al. [This TPD index behavior was partially questioned in a recent publication by Hsiao et al.  in whichn et al. . In thish et al.  in whichTau index  and the pressure negative variation over the LV time variation (-dP/dt) , another parameter used in the LV relaxation assessment, aiming at better studying myocardial diastolic velocity determinants by Doppler tissue in animal sample with left atrium (LA) and LV pressure catheterization and measurement. For the first time in this study, the LA hemodynamic data are investigated invasively in relation to the TPD indices presenting a significant association between them: the A' late diastolic velocity was significantly correlated with the dP/dt , and with the LA relaxation index . Additionally, there was an inverse and significant correlation with the LA final diastolic pressure, which also reflects indirectly the LA hemodynamic behavior . Another concern, regarding the diastolic evaluation in patients with probable CF, is the lack of an isolated TMD index reproducibility when evaluated in an altered rhythmic situation, as is the case of atrial fibrillation or sinus tachycardia. Some studies, including the TPD indices, have approached this problem recently. In 1999, Sohn et al. [When both methods (MTD and TPD) were used in E/E' ration, a strong and statistically significant correlation was obtained with the capillary pressure measured by catheter . Besides, the study allowed the verification of patients with E/E' ration > 10 predicting a pulmonary capillary pressure > 15 mmHg with 97% sensibility and 78% specificity, and this study has placed the E/E' ratio in a quite promising position, as a diastolic index, stimulating many other subsequent studies. Ommen et al. , while an et al.  studied n et al. , while eThe evidences of such transversal study commented here for small populations, and some of them not using the real gold-standard for comparison, can still be questioned regarding its validity. However, when information arises from some recent data from a group of people added, involving Doppler indices in patients with CF, there is an awareness of the prognostic prediction power in mortality regarding hard events in patient groups with chronic atrial fibrillation , survivaThe LV remodeling is generated by mechanical, neurohumoral, and possibly genetic factors which alter the ventricular dimension, morphology and function. It can occur in response to the aggressions in many clinical conditions including severe or chronic ischaemia, cardiomyopathies, hypertension and valvular and infectious disease. In the structural alteration diagram, hypertrophy, myocyte loss and the interstitial fibrosis increase, compose the tissue physiopathologic aspect associated with a progressive dysfunction. In its conception, the CF cause and consequence precepts are superimposed , as the The study of the changes in the association in ventricular geometry with the worsening of specific diastolic stages – LV relaxation, and compliance or stiffness – represents an interesting focus. While still insisting on the association between SAH and ventricular dysfunction remodeling in a patient with CF, it is important to remember that, in this case, the hypertrophy works as an adaptive mechanism for the LV pressure overload involving the muscular and non muscular heart compartment. Various studies suggest the role of the contractile protein increase in the myocyte with a subsequent increase of this cell, and followed by the collagen matrix remodeling and the sustained growth in the deposition of this element in the interstitial space. The natural history of this process is the worsening of the myocardium active relaxation and the increase of the chamber stiffness causing LV filling dysfunction . StudiesTau index, rectifying previous findings [Hypertension Research [HyperGEN Study [European Society of Cardiology [The hypertrophy relation with LV relaxation alteration has also been investigated and deserves some special consideration. In relation to patients with systemic arterial hypertension, Oki et al.  have stufindings . The clafindings  have fouResearch  a study Research , and meaEN Study  with 1,3rdiology  was obseThe discussion on the left atrial physiology must be preceded by a brief review of the liquid dynamic concepts and based on this, a combination with the basic notions of its wall contractility, compliance and relaxation biological properties. The LA is a functioning chamber more complex than it seems and it is not a LV simple appendix or a pulmonary vein final chamber but an structure with direct implication on the heart rhythm, on the pulmonary circulation and on the LV filling modulation, with a defined clinical importance and has been largely discussed in the real scenario in the heart failure syndrome, systemic arterial hypertension clinical context, and even in normal, athletic or sedentary patients . Even thThe remodeling indices and the left atrial function have already been related to systemic arterial hypertension, age and a variety of other situations, and the interaction with the LV function represents an important focus of interest to understand the CF myocardial physiopathology. The left atrium contractile function is the most emphasized item when this issue is discussed – LA and the LV function. The awareness regarding the contribution of the atrial systole for the increase of the relation LV pressure/final diameter has opened new perspectives for the understanding of the geometry relation model, the left atrium function and its relation with the LV . Kono etWake Forest University [However, what would be the correlation between the atrioventricular remodeling variables, LV myocardial dysfunction by pressure overload in heart adaptation initial stages to systemic arterial hypertension? In an attempt to clarify this question, a study by Tsioufis et al.  has showiversity  has studMayo Clinic, in which a cohort from Olmsted, Minnesota, USA was investigated with 1,375 elderly people (≥ 65 years of age) with preserved systolic function (≥ 50% of LV ejection fraction), it was identified that a left atrial volume ≥ 32 ml/m2 was an independent predictor for the first manifestation of CF (P < 0.001) in a follow up of 4.3 ± 2.7 years of age and a higher LA volume progression  was observed in follow up of people who developed CF [The Strong Heart Study [These findings emphasize the importance of the left atrium as an actor in CF patients independently of the case of depressed or preserved LV ejection fraction, validating the applicability of this parameter in patients in this age group with diastolic CF. In short, it is possible to state that there is some evidence support which points out to a clear idea of an interaction between the geometry data and the LV and LA function. The next step is to establish and to quantify the importance of all information for clinical handling. And, more recently, in agreement with this idea, many studies were published, transcending concepts obtained in a transversal way for studies of longitudinal follow up which emphasized this issue relevance. In at least four studies published in the last time, a left atrial index prognostic correlation could be observed. Tsang et al.  have obsloped CF . There art Study  conductert Study . Studiesrt Study . As in hThe diagnostic evaluation of the patient with a suspicion of CF is not always simple, mainly when there is a normal or slightly altered LV ejection fraction, since this is the case in half of the CF cases. The echocardiographic tools for diastolic evaluation, despite the improvement already attained, sometimes are not enough if they are analyzed separately Figure . The LV The authors declare that they have no competing interests.This review article is part of the doctoral thesis of the author LCD under orientation of MRT, his advisor; LCB and IK participated in the examining commission of the author (in order to obtain his degree) and helped much in the process of writing and reviewing o this manuscript. All authors read and approved the final manuscript.The authors declare that they have no source(s) of funding.


Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures. Over the past decade heart transplantation (HT) has evolved from a rarely performed procedure to an accepted therapy for advanced heart failure. About 45% of the candidates to HT have ischemic cardiomyopathy while 55% have some form of dilated cardiomyopathy of various origin. The prognosis for HT patients following the orthotopic procedure has greatly improved over the past 20 years, and a recent report (August 2006) of Heart Transplants: Statistics of American Heart Association. informs that the 5 years survival rates is 66.9% in women and 71.2% in men. Although significant advances have been reached in surgical techniques, in donor and recipient selection criteria, and also in the management of transplant patients, allograft rejection remains the most important cause of morbidity and. the primary limitation for the survival of these patients.Acute allograft rejection (AAR) is frequent in the first months after HT. Because it is initially asymptomatic, regular rejection surveillance is obligatory by monitoring immunosuppressive treatment, clinical and laboratory data and, in particular, by performing endomyocardial biopsies (EMBs), which represent the gold standard for the detection of rejection. AAR is characterised histologically by inflammatory cell infiltrates, interstitial edema and myocite necrosis which ultimately translates into structural and functional abnormalities of the allograft. A first international grading system for cardiac allograft biopsies, adopted in 1990 by the International Society for Heart Transplantation .Long-term survival of allografted hearts is limited by a progressive fibro-proliferative disease, resulting in intimal thickening and occlusion of the grafted coronary vessels. This disease, variously defined as accelerated transplant coronary artery disease (CAD) or cardiac graft vasculopathy (CAV), is also known as chronic allograft rejection ). After Echocardiography is particularly useful for the assessment of HT recipients since it is easily performable and not associated with the risks of the invasive procedures. Its versatility allows it to be applied in a wide variety of situations in the post-transplant setting.biatrial surgical approach) an anastomosis is made between the residual recipient atrial tissue and the donor atria such that there is a characteristic unique echocardiographic atrial morphological appearance. Therefore, transplanted hearts have increased size in both atria, primarily caused by an increase in their long-axis dimension. Sometimes, an echo dense ridge is also visualisable at mid-atrial level , it being the site of anastomosis between the residual recipient atrial tissue and the donor atria    ] .IMP is an index which combines LV systolic and diastolic parameters  and gives information about LV global performance . The ratAfter HT, it is evident an increase in wall thickness and LV mass, which can be detected and followed during time by serial echocardiographic examinations. LV hypertrophy is due to several causes  and its progression occurs mainly in relation to cyclosporine levels and blood pressure levels . It is wValvular regurgitation is a fairly common occurrence immediately post HT but structural abnormalities of the aortic and mitral valves are not observed frequently after HT. In a long-term follow-up study, only 13 of 65 patients had mitral valve regurgitation (no patients had severe regurgitation), three cases of aortic valve regurgitation were reported and no patient has significant aortic valve stenosis . PossiblIn contrast to the left-sided valves, tricuspid valve regurgitation is very common after HT, its etiology being multifactorial. When its appearance is early after HT, probably it is related to elevated pulmonary arterial pressures and vascular resistance in the recipient as well as to atrial structure and function . In the majority of the cases, the resolution of tricuspid regurgitation is possible within 1 month after HT, hand in hand with the normalisation of pulmonary arterial pressures . Tricuspm velocity of the lateral tricuspid annulus has demonstrated to be lower than in controls, showing a trend to a further reduction during time  after HT (18)  and specificity (= 74%) for diagnosis of AAR are limited  The possIntegrated backscatter (IBS) appears able to identify AAR by the decrease of cyclic variation signal [strain rate imaging (SRI), a tool which quantifies myocardial wall deformation and distinguishes "true" active myocardial contraction from passive wall motion [n signal  and the n signal . The offl motion , has beel motion . SRI migl motion  and reduSeveral attempts have been performed during time to take advantage by M-mode and 2-D echocardiography to diagnose AAR. The main echocardiographic variables proposed for diagnosis of AAR include increased wall thickness and wall echogenity, pericardial effusion, LV diastolic dysfunction and regional/global LV systolic dysfunction . Table 2Dobutamine stress echocardiography (DSE) identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies [m velocity and negatively with E/Em ratio in HT recipients: this findings indicates a possible association of impaired coronary microcirculation with both myocardial systolic dysfunction and increase of LV filling pressures in this clinical setting [The development of progressive CAD in HT has been recognised increasingly as long-term recipient survival has improved. Because CAV remains the major cause of death during long-term follow-up, its diagnosis is very important. It is remained for years in the prevalent domain of invasive techniques. Serial coronary angiography permits the study of coronary arteries and also the visualisation of coronary arteries by intravascular ultrasound (IVUS), that represents the reference gold standard in this clinical setting. Rapidly progressive vasculopathy by IVUS, defined as an increase of ≥ 0.5 mm in intimal thickness within the first year after HT, is a powerful predictor of all-cause mortality, myocardial infarction and angiographic abnormalities . However studies ,54,56. I studies . DSE has studies . The use studies . Also di studies ,62. Alth studies . Adenosi studies . A short studies . Figure  setting .Table Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy . The useHeart donor storage is a main problem since patients in HT waiting list have a 7.3% death rate and the average waiting time is 2 to 3 years. In addition, there is a large amount of ''marginal'' recipients, it being due to either advanced age (> 65 years) or co-morbidity. Of consequence, a gradual trend toward liberalizing donor selection criteria has been developed and an expansion of the cardiac donor pool has involved accepting hearts of older donors, tolerating longer organ ischemic times and accepting hearts with structural and/or functional abnormalities, such as mild LV hypertrophy and mild valvular abnormalities -72. In tTransthoracic Doppler echocardiography is a primary non-invasive modality for investigation of cardiac transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. Although sustained efforts to develop and echocardiographic technique able to predict the biopsy state have been performed, it has fair to recognise that EMBs are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately CAV and has recognised prognostic value, which is comparable to that of IVUS or angiography. A normal stress-echo justifies postponement of invasive studies. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. Finally, echocardiographic monitoring is simple and effective for monitoring a safe performance of biopsy procedures.The author(s) declare that they have no competing interests.SM conceived the study, participated in its design and drafted the manuscript, MM and MG reviewed the manuscript and participated in the design of the study, All the authors read and approved the final manuscript.


The mammalian Natriuretic Peptide (NP) system consists of neuro-hormones, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), c-type natriuretic peptide (CNP), and the N-Terminal fragment of BNP (NT-pro-BNP). In response to some cardiovascular derangement the heart (acting as an endocrine organ), brain and other structures secretes natriuretic peptides in an attempt to restore normal circulatory conditions. Their actions are modulated through membrane-bound guanylyl cyclased (GC) receptors. They induce diuresis, natriuresis and vasodilation in the presence of congestive heart failure. These neuro-hormones also play a role in the suppression of neointimal formation after vascular injury. In addition, they act as antifibrotic and antihypertrophic agents preventing cardiac remodeling after myocardial infarction. Further, NP have diagnostic and prognostic role in heart failure, vasoconstriction, left ventricular late remodeling after MI and others. At present, some drugs such as Nesiritide, NEP inhibitors and vasopeptidase inhibitors were synthetized from NP, to antagonize these cardiovascular derengements. In future, it will be possibile to elaborate some drugs similar to petidase inhibitors and some CNP-like drugs able to reduce many symptoms of cardiovascular derangements without significant side effects. Natriuretic Peptide (NP) System is composed of neurohormones synthesized by the heart, brain and other organsAtrial Natriuretic Peptide (ANP); Brain Natriuretic Peptide (BNP); C-type Natriuretic Peptide (CNP)N Terminal fragment of pro BNP (NT-pro-BNP) must be also considered. This last derives from the proteolysis of proform BNP.At present, the mammalian natriuretic peptide system consists of some substances: ANP is the first discovered member of this family. The major site of synthesis in normal heart is the atrium, and secretion is stimulated by stretch. In normal adult heart, ventricular tissue produces only minor amounts of ANP, but major amounts are found in ventricles of fetuses and in patients with LV hypertrophy. ANP is a 28-amino acid peptide stored and released by atrial myocytes in response to atrial distension and stretch. In addition, it also increases angiotensin II and/or endothelin rise-concentrations as a consequence of sympathetic stimulation.Elevated levels of ANP generally are found in hypervolemic states inducing a condition of congestive heart failure. It is present in patients with heart failure and chronic atrial fibrillation (AF). In this connection, ANP levels were higher among those with AF of longer duration than in decompensated patients with AF of shorter lengthBNP was primarily discovered in porcine brain, but the highest concentration of peptide is found in the heart. It is a 32 amino-acid peptide, synthesized within the ventricles in response to myocyte stretch and/or pressure overload8. It is released both as an active hormone and an inactive N-terminal fragment (NT pro-BNP). Recently, Elnomany and Abdelhameed found that BNP levels are elevated in patients with symptomatic LV dysfunction. The reduction of Mitral Annulus Posterior Excursion (MAPSE), as the index of left ventricular dysfunction, appears strongly correlated with plasma BNP levels. This correlation provides a simple, accurate and reproducible tool for early diagnosis of LV dysfunctionIn addition, BNP levels are higher in patients with dyspnea (shortness of breath) due to heart failure than in patients with dyspnea induced by other causes. Consequently, BNP measurement in the emergency room helps in to discriminate two types of dyspnea. Besides, BNP appears to be a useful marker of cardiovascular risk, even in persons without clinical evidence of cardiovascular disease. Finally, BNP levels were employed to predict the risk of heart failure atrial fibrillation and stroke or transient ischemic attack. Conclusively, the hemodynamic effects of BNP are largely similar to those of ANP.C-type Natriuretic Peptide was originally isolated from porcine brain extracts but, the major site of synthesis are the vessel walls. The peptide plays a role in the suppression of neo-intima formation after injuryNumerous compounds limiting ventricular remodeling after MI heve been reported. These include angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, aldosterone antagonists, and matrix metalloproteinase inhibitors. Although almost all these agents have been given orally contrary to CNP, this last has the advantage concerning short period of treatment and fewer side effects.N-terminal fragment of Brain Natriuretic Peptide (NT pro-BNP) derives from the proteolysis of pro-BNP (composed of 108 amino-acids). It consists of 76 amino-acids and recently caused great interest for its possible role in monitoring cardiac insufficiencyThe NP serum levels are important not only as indicators of numerous cardiovascular derangements, but also as markers of their severity. ANP are found elevated in patients suffering from MI and having congestive heart failureThis diagnostic value was recently confirmed by Coutance et al. Although elevated BNP levels have a high sensitivity to detect patients at risk of death, the specificity of this neuro-hormone is lowThe beneficial effects of NP on cardiovascular disease stimulated the development of new compounds able to prolong and enhance these positive effects. Of these:Nesiritide is a recombinant form of human BNP, approved for use in the acute treatment of congestive heart failure caused by systolic dysfunctionThe agent is indicated for intravenous treatment and has advantageous, pluripotent properties in ADHF including hemodynamic, neurohormonal, lusitropic, and reverse remodeling effects. In addition, it was satisfactorily compared with other vasodilating agents and did not promotes arrhythmogenesisSubsequently, a number of other drugs deriving from CNP have been prepared30More recently, a new class of drugs similar to NEP inhibitors have been shown to be efficacious in animal models with heart failure. Treatment with NEP-inhibitor, Candoxantril, increases urinary sodium and significantly elevates filtration fraction with no significant effect on glomerular filtration rate, renal plasma flow or lithium clearance. A reduction in aldosterone concentration is also evident in these patients34There are, however, complex interactions between ACE and NEP inhibition. Both ACE and NEP metabolize the kinin peptides bradykinin and kallidin, whereas NEP converts angiotensin I to angiotensin and metabolizes Angiotensin II and endothelin. Addition of NEP inhibition to ACE inhibition potentiates the ACE-inhibitor-induced increase in kinin levels. But, the combined ACE/NEP inhibition increases the risk of angioedema and may counteract any benefit of ACE inhibitionConclusively, NP is an endogenous system able to induce most common circulatory derangements, such as water retention, vasoconstriction in response to CHF. In addition, the system causes endothelial dysfunction and left ventricular late remodeling. To avoid these negative effects, new derived drugs are recently prepared to reduce, eliminate or delay the symptoms of cardiac and vascular impairments. They act by performing some cardiovascular and renal actions such as: natriuresis; increase of glomerular filtration; systemic vasodilation; inhibition of renin release; reduction of left ventricular remodeling; reduction of venous and “wedge” pressure.These drugs must be able to attain, extend, and stabilize neuro-hormonal, hemodynamic and clinical improvements of symptoms of some cardiovascular disease, such as chronic heart failure, myocardial infarction or systemic hypertension. In future, these drugs will become more and more important, because they act by addressing common cardiovascular symptoms through endogenous principles, which allows resolution of symptoms or retard progression of symptoms without adverse side effects.


Pulsus alternans is a rare hemodynamic condition characterized by beat-to-beat variability in systolic pressure. It is attributed to variations in stroke volume with alternate cardiac cycles and is typically seen in patients with advanced myopathic conditions. Left ventricular pulsus alternans is rare, and right ventricular pulsus alternans is even less common. There are only a few reports of biventricular pulsus alternans. We report the case of a 62-year-old female with a recent anterior wall myocardial infarction who had biventricular pulsus alternans at the time of cardiac catheterization. A 62-year-old female with diabetes mellitus and hypertension developed what she thought was the “flu” associated with orthopnea, shortness of breath, and chest pressure. She presented to her local physician 3 weeks later when the symptoms persisted and were accompanied by a 15–20 pound weight gain. Her BNP was markedly elevated and a chest X-ray showed cardiomegaly with bilateral pleural effusion. ECG and echocardiogram were consistent with a recent anterior wall myocardial infarction.Cardiac catheterization after a 15 pound diuresis showed severely reduced left ventricular systolic function with an ejection fraction of 31%. Left heart filling pressures were elevated with a left ventricular end diastolic pressure of 26 mmHg and pulmonary capillary wedge pressure of 28 mmHg. She had severe disease of the mid left anterior descending coronary artery which was treated with placement of a drug-eluting stent. During the procedure, the patient had beat-to-beat alterations evident in aortic, pulmonary artery, left ventricular, and right ventricular pressures  in the aIn the nine months since her cardiac catheterization, she has had no recurrent heart failure, angina, or myocardial infarction. She remains active and has NYHA class II symptoms on a medical regimen that includes metoprolol (25 mg BID), quinapril (40 mg qD), and furosemide (20 mg qD).++ transients and the development of pulsus alternans in a mouse model [Pulsus alternans was originally described more than 100 years ago. It is a rare finding in the left ventricle and even less common in the right ventricle. The cause of pulsus alternans has not been clearly delineated, and there is some speculation that different mechanisms may play a role dependent on the patient. One proposed mechanism is beat-to-beat alternations in stroke volume due to variation in preload and contractility. Impaired systolic contraction of a failing ventricle reduces stroke volume which then results in elevated end diastolic volume for the next contraction. Elevated left ventricular stretch results in increased stroke volume and therefore increased systolic pressure on the next beat . In suppse model .Severe left ventricular systolic dysfunction is the primary cause of pulsus alternans but other causes have been reported in humans including aortic stenosis , 5, hype