Truncus arteriosus (TA) is a rare congenital condition defined as a single arterial vessel arising from the heart that gives origin to the systemic, pulmonary and coronary circulations. We discuss the unique case of a 28 year-old female patient with unrepaired TA and interruption of the aortic arch who underwent cardiovascular magnetic resonance (CMR). Truncus arteriosus communis (TA) or common arterial trunk is an uncommon congenital cardiac malformation accounting for approximately 0.7% of all complex congenital heart lesions. TruncusCollette and Edwards described four types of TA lesions based on the origin of the pulmonary arteries. A Type Interruption of the aortic arch (IAA) is found in approximately 11-19% of children with TA lesions -6. InterThe prognosis of patients with TA lesions is poor without surgical intervention. Newborns often present with signs of florid heart failure and cyanosis. Surgical intervention is required to avoid pulmonary vascular disease that would likely ensue in the unrepaired patient. Improving surgical techniques has led to the long-term survival of these patients. Here weA 28-year old female with a history of unrepaired TA presented to the Adolescent and Young Adult Congenital Clinic for a second opinion regarding pregnancy counseling.Initially, she reported a history of cyanosis with crying as a toddler, with subsequent diagnosis of underlying complex cyanotic congenital heart disease at age three years. Her past medical history was also significant for a cerebral abscess requiring craniotomy in 2002 with no residual neurologic defects. After this hospitalization, she was listed for heart-lung transplantation. In the interim, she had been initiated on bosentan therapy with improvement in cardiovascular symptoms. Subsequently, transplantation was not pursued. Cardiac catheterization one year later demonstrated a pulmonary artery pressure of 115/64 (mean 85 mmHg) and right atrial, pulmonary artery and arterial oxygen saturations of 44%, 84% and 78% respectively. The hemodynamics remained unchanged with administration of nitric oxide. After this procedure, sildenafil was added to her therapy with bosentan.The patient had recently married and was actively trying to become pregnant, despite prior recommendations advising against pregnancy in light of the underlying congenital condition and severe pulmonary hypertension. Therefore, she presented for a second opinion regarding pregnancy counseling.The patient proceeded to undergo CMR to better delineate her complex anatomy and cardiac function. A negative pregnancy test was obtained prior to scanning. Images were obtained with a 1.5 Tesla system  with maximum gradient strength of 45 mT/m, slew rate of 200 mT/m/sec, and a 12-channel array coil with 6 anterior and 6 posterior elements. The imaging protocol included: (1) axial, sagittal and coronal half-Fourier single-shot echo train spin echo (HASTE) imaging; (2) navigator-echo acquisition covering the whole heart and great vessels; (3) steady-state free precession (SSFP) cines of the vertical long-axis, horizontal long-axis, 3-chamber, ventricular outflow views; (4) SSFP cine-stack of short-axis views from base to apex for assessment of left and right ventricular function; (5) gadolinium (0.2 mmol/kg gadopentetate dimeglumine)-enhanced 3-D T1-weighted gradient echo sequence with the slab positioned for an MRA acquisition of the common trunk, arch vessels, central pulmonary arteries and the descending aorta; (6) in- and through-plane velocity-encoded imaging of the truncal valve; and (7) late gadolinium enhancement imaging using an inversion-recovery single-shot balanced SSFP sequence with the TI optimized to null normal myocardium.2), with LV ejection fraction of 52%. The right ventricle (RV) was also normal in size (72 mL/m2) with moderate concentric hypertrophy and RV ejection fraction 51%. Systolic flattening of the interventricular septum was present suggesting right ventricular pressure overload  hypertrophy and systolic flattening of the interventricular septum suggest evidence of RV pressure overload.Click here for file


Transvenous pacing is a relatively safe treatment with a low complication rate, but serious thromboembolic complications have been reported to occur in 0.6% to 3.5% of cases. Superior vena cava obstruction syndrome is generally an uncommon but serious complication occurring in <0.1% of patients. However, when it occurs it carries with it significant morbidity and mortality.A 51-year-old lady with long history of DDD permanent pacemaker presented following a mechanical fall. She had no obvious injuries, and was hemodynamically stable. General examination revealed features suggestive of Superior vena caval obstruction which was later confirmed by imaging. She was treated with long term oral anticoagulation with good clinical improvement.Superior vena cava obstruction in patients with transvenous pacing leads, although rare, is a well recognized complication. With growing elderly population and increasing number of procedures performed, more and more people with permanent pacemaker are likely to be encountered in clinical practice. One should carefully look for thromboembolic complications during follow-up in patients with transvenous pacemaker leads, as it has implications for future management and carries significant morbidity and mortality. Although transvenous pacing is a relatively safe treatment with a low complication rate , seriousThis 51-year-old Caucasian lady presented following a mechanical fall. Nine years previously she had had a DDD permanent pacemaker implanted on her left hand side for stokes adams attacks due to second degree atrio-ventricular block. One year ago, she presented with her pacemaker eroding through the skin and then had another pacemaker implantation on right hand side. Old atrial lead was extracted while ventricular lead could not be extracted and was cut short to be left in situ.This time she presented following a mechanical fall. On examination, her vital signs were stable. General examination revealed a raised jugular venous pressure, distended neck and chest veins and right arm swelling, consistent with SVCO. She had no clubbing, lymphadenopathy, or breast lumps. The rest of her systemic examination was unremarkable.Her chest X-ray showed the pacemaker leads in situ . ComputeThere are variable reports about the incidence of venous obstruction after pacing lead implantation ranging from 0.6% to 30% ,8. Much The mechanism is believed to be mechanical stress induced by transvenous leads, eliciting vascular wall inflammation and fibrosis ultimately leading to venous thrombosis and occlusion . AlthougNo significant differences was observed between obstruction and non-obstruction groups in terms of age, sex, cardiothoracic ratio, left atrial dimension, left ventricular ejection fraction, baseline heart diseases for indication of pacemaker implantation, or number and body size of pacing leads . Da CostAnother recently published study, looking at 100 consecutive patients for elective permanent transvenous pacemaker, did not find any significant difference between two groups in the incidence of venous abnormalities according to the route of entry, the lead insulation or the total number of the implanted leads .Data regarding treatment options for SVCO are limited. Contrary to the treatment of SVCO caused by malignant tumors, treatment for benign causes of superior vena cava obstruction is often protracted, punctuated by multiple episodes of recurrences. These causes include arterio-venous shunt, central lines and cardiac pacing wires. Venous angioplasty and stenting in these patients are often repeated, with cumulative patency approaching 80% at 2 years ,16.In cases related to cardiac pacing wires, removal of the device is not only undesirable [in view of the cardiac arrhythmia], but it is also often impossible and may not relieve the symptoms. The leads, which are insulated by silicon, are covered by endothelium and become incorporated into the vascular wall . The pacVarious modalities of treatment that can be considered include long-term anticoagulation as adopted in our case, thrombolytic therapy, surgical intervention, percutaneous transluminal balloon venoplasty and metallic stent insertion. Options depend on the duration, extent, and site of venous occlusion as well as the accompanying symptoms . A recenSVCO in patients with transvenous pacing leads, although rare, is a well recognized complication. SVCO can interfere with intravenously administered therapy, monitoring of central venous pressure and revision of a pacemaker lead. With growing elderly population and increasing number of procedures performed, more and more people with permanent pacemaker are likely to be encountered in clinical practice. One should carefully look for thromboembolic complications during follow-up in patients with transvenous pacemaker leads, as it has implications for future management and carries significant morbidity and mortality.


Hind III polymorphism of Plasminogen activator Inhibitor-1 (PAI-1) gene with idiopathic pulmonary arterial hypertension (IPAH).The aim of the present study was to identify the possible genotypic association of 3’UTR IPAH is a disorder with abnormally raised mean pulmonary arterial pressure and increase in the resistance to blood flow in pulmonary artery. One of the pathological features seen is development of intraluminal thrombin deposition leading to thrombosis. Plasminogen activator inhibitor-1 is an important inhibitor of the fibrinolytic system; its up-regulation may suppress fibrinolysis and result in an increased risk of thrombosis.Hind III polymorphism.Blood samples from 54 IPAH patients and 100 healthy voluntary donors were analyzed by PCR-RFLP method for 3’UTR A significant association of Hd2 allele with the disease was observed. Raised mean level of right ventricular systolic pressure was observed in the Hd2/Hd2 genotypic patients, strengthening the role of Hd2 allele in the disease progression. Our data suggests an association of Hd2/Hd2 genotype, which may lead to the up-regulation of PAI-1 gene leading to increased levels of PAI-1, which is seen in IPAH. PAI-1 competes with plasminogen activators and hinders the normal mechanism of plasminogen activation system and leads to thrombosis and formation of plexiform lesions in the lung tissue, further strengthening its role in tissue remodeling and disease progression. Primers sequences used: forward primer: 5’ AGCAATCCACCTGTCTCGGC 3’, reverse primer: 5’ TCCTGACCTCAGGTGATCCG 3’. as presented in 2 5.33; P < 0.05), with predominance of Hd2 allele in female patients.The frequency distribution of PAI-1 genotypes with respect to gender is shown in Hemodynamic parameters are influenced by the disease progression with progressive rise in pulmonary vascular resistance. Increase in the right ventricular systolic pressures [equivalent to the pulmonary artery systolic pressures (sPAP)] is associated with right ventricular failure, which can be obtained by calculating the right ventricular pressure gradient and right atrial pressure (RAP) gradient.The mean levels of RVSP with respect to PAI-1 genotypes were (X±SD) 101.90 ± 24.84 for Hd1/Hd1, 100.52 ± 30.79 for Hd1/Hd2, and 102.29 ± 16.23 for Hd2/Hd2, with mean RVSP being higher in the Hd2/Hd2 genotypes, further supporting the Hd2 association with IPAH; and the association can be correlated to the severity of the disease, increased mPAP pressures, and Tricuspid regurgitation (TR) velocity .Synthesis and expression of PAI-1 at transcriptional level are, to a large extent, stimulated by transforming growth factor β-1 (TGF β-1), released from the alpha granules of platelets after vascular injury. In the pAn interesting observation of the study was the predominance of Hd2 allele in women that was found to be significantly associated with the disease. Since female preponderance is reported in IPAH, it is poThe odds ratio of Hd2 allele was found to be significant when compared to HD1 allele in IPAH. . This observation further supports the earlier reports that have implicated the Hd2 allele for the increased levels of PAI-1. Elevated PAI-1 levels impair the fibrinolytic pathway by competing with tissue plasminogen activator (t-PA), thereby inhibiting plasminogen activating system. Thrombosis of pulmonary vessels is a common finding in IPAH, where it is found with a frequency of 30% to 60%.[16] These thrombotic events are likely to be involved in the progression of the disease by hindering tissue repair and thus contributing to the altered vasculature/architecture that is commonly seen in IPAH.With respect to clinical parameters, an increase in the mean level of right ventricular systolic pressure was observed in the Hd2/Hd2 genotypic patients, strengthening the role of Hd2 allele in the etiopathogenesis of IPAH in correlation to severity and poor prognosis.Our data suggests an association of Hd2/Hd2 genotype with the disease, and may be responsible for up-regulation of PAI-1 which competes with plasminogen activators and impairing the normal mechanism of plasminogen activation system. This activation may contribute significantly to IPAH by promoting thrombosis and fibrosis, leading to tissue remodeling of the lung. The Hd2 allele could be a predisposing factor for female preponderance in IPAH, but this needs to be ascertained on a larger sample size.


Biventricular (BiV) is extensively used in the treatment of congestive heart failure but so far no recommendations for optimized programming of atrioventricular-delay (AVD) settings have been proposed. Can AVD optimization be performed using a simple formula based on non-invasive doppler-echocardiography?25 patients (ejection fraction 30±8%) received BiV ICDs. Doppler-echocardiographic evaluation of diastolic and systolic flow was performed for different AVDs (30ms to 150ms) and different stimulation sites (left ventricular (LV), right ventricular and BiV). The optimal atrioventricular delay was calculated applying a simple formula based on systolic and diastolic mechanical delays determined during doppler-echocardiography.The mean optimal AVD was calculated to be 112±29ms (50 to 180ms) for BiV, 95±30ms (65 to 150ms) for LV and 75±28ms (40 to 125ms) for right ventricular pacing with wide interindividual variations. Compared to suboptimal AVDs diastolic optimization improved preejection and ejection intervals independent to pacing site. Optimization of the AVD significantly increased ejection time during BiV pacing . Compared to LV or right ventricular pacing BiV pacing produced the shortest mean pre-ejection and longest ejection intervals as parameters of improved systolic ventricular contractile synchrony. Diastolic filling times were longest during BiV pacing compared to LV or RV pacing.Individual programming of BiV pacing devices increases hemodynamic benefit when implementing the inter-individually widely varying electromechanical delays. Optimization applying a simple formula not only improves diastolic ventricular filling but also increases systolic functional parameters. Systolic resynchronization using biventricular (BiV) pacing has evolved as an established add-on therapeutic option in patients with symptomatic congestive heart failure. When pacing the left ventricle via the coronary sinus the contraction pattern of the interventricular septum and the contraction sequence of both ventricles is improved. This therapy has proven to increase systolic function (dP/dt) and cardiac function -5.In patients with left ventricular pump failure conventional dual chamber pacemakers have been shown to alter hemodynamics in regard to the programmed atrioventricular delay (AVD). A long AVD leads to atrial contraction too early for optimal ventricular filling . On the other hand a short AVD may lead to atrial contraction after closure of the atrioventricular valve (due to systolic increase of ventricular pressure) -10.Different methods have been proposed to determine the most favorable  AVD aiming at either optimizing systolic or diastolic cardiac function. Diastolic optimization of the AVD aims at restoring the atrial kick by coincidental timing of the end the left atrial systole and the mitral valve closure ,6,11-17.We studied the feasibility and efficacy of AVD optimization adapting a modification of a formula for optimal AVD programming in patients under biventricular stimulation with intrinsic atrioventricular conduction and left ventricular insufficiency. The effects on non-invasively determined parameters of cardiac systolic and diastolic function     were assessed. 25 consecutive patients were included after implantation of biventricular implantable defibrillators (ICD) (Medtronic InSync™ ICD) for chronic heart failure class II to IV in between 1999 and 2001. All patients gave informed consent; the protocol was evaluated by the institutional ethics review board.In all patients a standard ECG (12-lead) and Doppler-echocardiographic studies were performed 30 days after implantation. Different AVDs were programmed  for the 3 programmable stimulation sites . Fusion beats were excluded on the basis of QRS morphology. For each programming mitral- and tricuspid-valve and aortic valve Doppler-echocardiograms were performed using our Hewlett Packard Sonos 5500 echocardiography system with continuous display of ECG at a paper speed of 100mm/sec. Measurements were performed after a resting period of 1 minute in intrinsic rhythm. Prior to each measurement an adapting period of 1 minute was established. 3 consecutive atrioventricular and aortic valve flow profiles were analyzed and different time intervals were measured see  and the Mitral valve diastolic filling time: Measure of diastolic left ventricular filling.Tricuspid valve diastolic filling time:Measure of diastolic right ventricular filling.Pre-ejection time:Indicating the intra- and interventricular conduction and contraction synchrony.Ejection time:Measure of left ventricular ejection.As a next step the AVD producing the most favorable diastolic left ventricular inflow  was calculated applying a simple formula see : Two steLong AVD pacing (150 to 200ms) to determine the atrial electromechanical delay:The atrial electromechanical delay constitutes the time interval in between the right atrial sensed electrical impulse to the end of the active mitral valve flow. This includes the interatrial conduction time and the electromechanical coupling of the left atrium. This interval is intraindividually fixed and has a wide interindividual variation.Short AVD pacing (30ms as the shortest programmable AVD) to determine the isovolumic contraction time:The isovolumic contraction time is the time interval in between the ventricular electrical stimulation and the closure of the mitral valve due to the left ventricular systolic pressure increase. This interval can be measured when the atrial contraction is attenuated by the ventricular systole as documented in Doppler-echocardiography. This interval is intraindividually fixed and includes the conduction time from the pacing electrode to the left ventricle, the electromechanical coupling of the left ventricle and the duration from the beginning of the left ventricular systole to increasing intraventricular pressure above atrial pressure.Calculation of the optimal AVD when subtracting the atrial electromechanical delay and the isovolumic contraction time .When the calculated optimal AVD was different from the before programmed AVDs measurements were performed after optimized programming.In each patient, measurements during optimized pacing  were compared to the mean of the three AVDs  (= control) excluding the optimal AVD .The means of the 3 consecutive measurements were calculated and the optimal AVD was calculated for each patients. Non-categorical variables of the different pacing site groups  and different AVDs  were compared using Student t-test. Treatment effects within the groups (optimized pacing versus control settings) were assessed by ANOVA analysis. A significant difference was proposed when p < 0.05.25 patients with a mean ejection fraction pre-implant of 30%  and mean end diastolic diameter (echocardiography) of 66mm (± 7) were analyzed. Mean age was 65 (±10)years, 22 had left bundle branch block morphology whereas 3 had right bundle branch block morphology and mean intrinsic QRS width was 191 . Position of the LV pacing lead was posterolateral in 16 (64%), lateral in 6 (24%) and anterior in 3 (12%).All patients were in sinus rhythm . Mean QRS width was significantly shortened during BiV pacing to 162ms (± 23) (p = 0.02), significantly longer during LV-pacing (238ms ±35) (p = 0.001) and significantly longer during right ventricular pacing (231ms ±39) (p = 0.006).Heart rate did not significantly differ intraindividually (± 5 bpm) during any of the Doppler-echo studies. A consistent finding was the consecutive shortening of the diastolic filling times  when prolonging the programmed AVD see . LV paciLongest mean ejection period resulted during BiV pacing compared to the monoventricular pacing modes independent to the programmed AVD. LV pacing seems to produce a longer ejection time compared to right ventricular pacing except at the shortest programmed AVD (30ms) see .1 of the 25 patients (4%) had no atrial contraction documented during transthoracic Doppler-echo. This patient was conclusively not eligible for optimization of the AVD. 24 of the 25 underwent Doppler-echocardiographic AVD optimization. The optimal AVD during BiV pacing was found to range in between 50ms to 180ms with a mean of 112ms (± 30). When correlating the optimal AVD to the intrinsic PQ-interval  it was found to translate into 23% to 80%, indicating a shortening of the PQ-interval in between 20% to 77% to gain optimized BiV pacing. The optimal AVD during LV pacing was found to be 95ms (± 30) (p = 0.95 vs. BiV) (65ms to 150ms) and during right ventricular pacing was significantly shorter compared to BiV pacing at 75ms (± 28) (p = 0.003) (40ms to 125ms) see .BiV optimized pacing produced the most favorable systolic and diastolic functional Doppler parameter compared to LV and right ventricular pacing see . StatistAVD optimization compared to control settings during BiV pacing significantly increased ejection time from 266ms (± 30) to 279ms (± 25) (p = 0.03) correlating with an improved systolic ejection see . The preDuring LV-pacing AVD optimization increased ejection time from 266ms (± 30) to 268ms (± 33) (p = 0.96) and pre-ejection time was shortened from 177ms (± 31) to 166ms (± 35) (p = 0.32) see . DiastolDuring optimized right ventricular pacing ejection period stayed constant at 263ms (± 35)  but pre-ejection time was shortened from 189ms (± 27) to 182ms (± 25) (p = 0.32) see . DiastolThere is still controversy about the effects of different programmings of the AVD in patients with pacing devices for chronic heart failure. Studies have emphasized the influence of the optimal pacing site in patients treated with biventricular pacing and there seems to be a beneficial effect of different AVD programmings modulating systolic ventricular function ,16,23.This study demonstrates improved systolic and diastolic function after non-invasive diastolic optimization on patients with implanted biventricular pacing devices. The optimal AVD was determined using a simple formula derived from findings in patients with complete heart block and is based on Doppler-echocardiographically measured electromechanical time intervals. Applying calculated optimal AVD programming diastolic filling is optimized and systolic function is improved. Improvements in systolic function may be due to a leftward shift in the Frank-Starling curve initiated by improved diastolic function. Although, optimizing the AVD may not lead to chronic increase in systolic function. Only a single report exists indicating functional improvement in biventricular pacing patients due to AVD optimization more than one month after optimization .Different studies have evaluated the effects of different AVD optimization strategies. In most cases, the optimal AVD was determined by echocardiographic parameters of systolic function (e.g. left ventricular outflow). A recent study on 215 patients undergoing cardiac resynchronization therapy indicated the usefulness and safety of AVD optimization using Doppler mitral inflow data . ControvWe documented beneficial effects on systolic functional Doppler parameters indicating improved ventricular ejection and beneficial effects on intra- and interventricular electrical synchronization when coincidentally timing the end of the left atrial contraction and the beginning of the left ventricular systole. The optimal AVD can easily and non-invasively be calculated using a formula integrating two time intervals measured during long AVD and short AVD pacing. This formula was proposed by Ritter et al. in 1995 for patients with complete AV-block to resynchronize left atrial and ventricular systole enabling optimal ventricular filling and pre-load. However this formula has not yet been validated invasively -22. In oApplying the calculated optimal AV-delay not only led to optimized timing of the atrial contraction just prior to the left ventricular systole but also produced changes in systolic functional Doppler parameters. During BiV pacing non-invasive diastolic AVD optimization significantly increased ejection time (5% increment compared to control settings). This implements significantly improved left ventricular systolic function only by modulating the AVD settings. Even though the correlation between ejection time and ejection volume is weak it is a measure of systolic ejection function indicating increased contractile function. Also AVD optimization led to shorter pre-ejection times documenting improved intra- and interventricular synchronicity. These findings are consistent with the documented changes of systolic function by Kindermann et al. when tailoring diastolic flow ,21. The 22It seems possible to improve the beneficial effect of electric resynchronization therapy by careful and Doppler-echo guided individual programming of biventricular pacing devices. Even though, no guidelines for programming parameters for AVD optimization are available ,16,24-28It is well known that the effect of pacing therapies for chronic heart failure depend on selection of the pacing site. Whereas right ventricular pacing was shown to have controversial effects on left ventricular performance left ventricular based pacing seems to have beneficial effects on systolic function due to electrical resynchronization of the left ventricular contraction pattern ,16,18-23As indicated in our study not only the filling volume but the preload which can be increased by optimal timing of the left atrial contraction and its contribution to ventricular filling is crucial for left ventricular performance. During optimized pacing the diastolic filling time is shorter than during short AV-delay pacing but correct timing of the left atrial contraction leads to optimized ventricular filling and readjusted mitral valve Doppler flow. These considerations explain the shorter diastolic filling times during optimized pacing compared to the suboptimal AVD programmings but still improved cardiac function during AVD optimization ,18-22,28This study is limited by the small number of patients included making it impossible to determine any variables leading to changes in optimal AV-delay settings like LV-electrode position, cardiac disease or ejection.As control the mean of AVD settings of 80ms, 100ms and 150ms were calculated and compared to optimized AVD pacing. This artificially constructed control setting is usually close to the range of the optimal AVD and therefore differences in between AVD settings may be marginal. On the other hand this control may resemble manufacturer's AVD settings implemented in the BiV pacing devices and therefore the analysis indicates the incremental benefit of AVD optimization compared to baseline settings.We did not perform any invasive hemodynamic studies to validate the applied formula for AV-delay optimization. Even though the documented improvements in Doppler echocardiographic functional parameters indicate hemodynamic benefit this has not been clinically tested. In addition, no comparative study to other methods of AVD optimization was performed. It remains unclear, whether the proposed formula leads to the highest benefits or if other strategies (e.g. tailoring systolic Doppler-echo parameters) may further increase hemodynamics.Especially in the latest pacing devices for biventricular resynchronization not only atrioventricular delay but also interventricular delays are programmable. Therefore there is a definitive need for guidelines or recommendations how to program different parameters of diastolic and systolic synchronization in these devices.Individual programming in patients under biventricular stimulation can increase the benefit of the resynchronization therapy when implementing the differences in electromechanical delays. Optimization of the AVD integrating these individual intervals can easily and non-invasively be performed using Doppler echocardiography applying a simple formula. Optimized pacing cannot only improve diastolic but also optimize systolic functional Doppler parameters.


A 73-year-old woman with dementia was given clozapine for treatment-resistant psychotic symptoms. Subsequently, she developed cardiac failure. Caution should be exercised when using clozapine, especially in the elderly. The efficacy of clozapine in treatment-resistant schizophrenia is well documented. It is also useful in the management of psychotic symptoms of dementia but should be used with caution due to its broad side-effect profile.M, a 73-year-old woman, was on treatment for dementia of the Alzheimer type with delusions (DSM-IV 290.12) for the past 3 years. As the psychotic symptoms did not respond to various antipsychotics, she was put on clozapine. Considering her age and the known adverse effects of the drug, a cardiology consultation was done on 13 December 2005. Clinical examination, ECG and echocardiogram were normal. Clozapine was started the next day at a dose of 12.5 mg/day, and gradually increased to 100 mg/day. On 5 January 2006 she developed breathlessness. Clinical examination showed signs of cardiac failure with sinus tachycardia and poor R wave progression in V1–V3. An echocardiogram revealed global left ventricular hypokinesia, mild left ventricular systolic dysfunction, a left ventricular ejection fraction of 40% and moderate mitral regurgitation. Clozapine was stopped. She responded to conventional antifailure measures.The temporal relationship between the introduction of clozapine and onset of cardiac failure suggests that the drug was responsible. However, she could have had independent age-related myocardial dysfunction. The classical features of myocarditis were absent. The maximum pulse rate in our patient was 92/min whereas in a recent case reportThe clinical features of myocarditis are varied. The spectrum includes asymptomatic patients who may have electro-cardiographic abnormalities; patients with signs and symptoms of clinical heart failure and ventricular dilatation; and patients with symptoms of fulminant heart failure and severe left ventricular dysfunction, with or without cardiac dilatation.


Prolonged pacing from the right ventricular (RV) apex has been shown to be associated with progressive left ventricular dysfunction as demonstrated by heart failure, atrial fibrillation and an increased morbidity and mortality -6.  ThisThese early reported studies involved using a lead stylet shaped with a simple curve which has been shown to position only 61% of leads onto the RV septum with the remainder on the anterior or free walls . Hence wNow that we have the surgical tools for lead placement onto the RV septum and a simple method of confirmation, it behooves us as physicians to repeat the earlier studies, but this time confirming septal positioning. One concern, however, is how long the clinical trials should be conducted?  As stated earlier, most studies were either acute or lasted about six months. Tse et al   comparedTo determine the optimal site for RV pacing, two multicenter randomized trials are currently underway. These are the Right Ventricular Apical and High Septal Pacing to Preserve Left Ventricular Function (Protect Pace), and Right Ventricular Apical versus Septal Pacing (RASP) trials. In Protect Pace, enrollment is almost complete and the mid septum is the pacing site. The RASP study has the inflow septum as the pacing site, The two studies have different study designs and protocols but all will analyze the long term (24 - 36 months) effects of RV pacing on LV performance indices and functional capacity, with changes in LVEF being the primary outcome [


The incidence and prevalence of dyspnea increases with age. Frequently, for the general practitioner with his limited diagnostic facilities, it is impossible to separate dyspnea from cardiac causes and non-cardiac causes. Without cardiac imaging it is also impossible to separate systolic dysfunction from diastolic dysfunction. After a thorough physical examination, initial screening of systolic and diastolic heart failure can be done by measurement of plasma NT-pro BNP or plasma BNP. Additionally a Chest X-Ray or ECG can be performed. To improve diagnostic performance an open access echocardiographic service can be initiated. Recent studies showed, that open access echocardiography can easily detect systolic and diastolic dysfunction in the community and can separate cardiac from non-cardiac dyspnea. Heart Failure has become a main cardiac problem in the modern western society with a prevalence of 2-6% of the population or five million cases in the United States ,2. The c1).The term diastolic heart failure is used to describe group of patients with the clinical signs of congestive heart failure and normal diastolic volume and predominant abnormalities of in relaxation and increased passive stiffness ,11. TherThe main approach to the patient with dyspnea is based on the history, physical examination, chest x-ray, and a series of laboratory diagnostic tests to establish the diagnosis, determine the etiology, and assess severity of heart failure. According to the Framingham data , heart fSeverity of of symptomatic heart failure can be classified according to the criteria of the New York Heart Association, where: Class I indicate symptoms only at activity levels that would limit normal individuals Class II indicate symptoms with ordinary exertion Class III indicate symptoms with less than ordinary exertion and Class IV indicate at rest.1 [For a complete work-up of a heart failure patient, the initial evaluation includes the investigations in Table 1 .Natriuretic peptides are released in respond to increased intracardiac volume and pressure  and are The level of BNP in plasma may also reflect diastolic dysfunction as has been shown in several studies ,23. ElevDiastolic heart failure is very common, especially in elderly women . Patientisovolumic relaxation time (IVRT) is the time between aortic valve closure and mitral valve opening and represents dynamic left ventricular relaxation [Diastolic function can be measured with echo-Doppler imaging by interrogation of mitral inflow and pulmonary vein flow using pulsed-wave Doppler and tissue Doppler imaging of mitral annular motion. Using pulsed-wave Doppler at the mitral valve annulus, several parameters can be measured . Left ventricular laxation . Normal laxation . The IVRlaxation . E/A ratio, which normally is less than one See also Fig. (2).Pulsed Doppler interrogation of the mitral annular flow reveals a peak E wave and a peak A wave. The peak E wave measures the early diastolic transmitral pressure gradient and thus reflects the rapid filling phase. Normal values are between 70 and 100 cm/s. The peak A wave measures the late diastolic transmitral pressure gradient and thus represents atrial contraction. The normal value is 45 to 70 cm/s. The overall characterization of left ventricular filling is by the Mitral deceleration time reflects left ventricular compliance in early diastole and is normally between 160 and 220 msec. In normal young adults, there is a predominance of early diastolic filling (E wave) with only 10% to 15% filling caused by atrial contraction. With the normal aging process, relaxation slows and causes reduced filling in early diastole and increased filling by atrial contraction [impaired relaxation , pseudonormalization , and restrictive filling [                traction . In pati filling . With a pseudonormal filling pattern. With this pattern, the E/A ratio is 1 to 1.5, and the deceleration time is normal. In more advanced disease, high atrial pressures (> 22 mm Hg) cause blood to rapidly fill the slowly relaxing left ventricle in early diastole. A marked increase in early left ventricular diastolic pressure results in only limited additional filling. The pulsed wave (PW) flow pattern is now known to be restrictive with a high velocity of the E wave, an E/A ratio more than 2, and a short deceleration time of less than 160 msec.A more severe compliance reduction and increase of left atrial pressure to 15 to 22 mm Hg results in a left ventricular filling pattern that appears normal but actually is not; this pattern is called a Because transmitral flow patterns are load-sensitive, additional measurement of pulmonary vein flow is helpful is assessing left ventricular filling . With exThe normal pulmonary vein flow shows a systolic flow (S) that is higher than the diastolic flow (D) with an atrial reversal flow (A).Patients with impaired relaxation have a normal pulmonary vein flow pattern. Patients with pseudonormalization and restrictive filling have a decrease of the S wave compared with the D wave and a pulmonary vein A wave flow reversal of > 35 cm/s. , and two-dimensional color maps. Imaging is usually performed from the apical window. From this view, the axial motion of the ventricle is parallel to the transducer axis, and velocities are primarily related to left ventricular contraction and relaxation. The pulsed-wave sample volume is mostly placed within the septal and lateral regions of the mitral annulus.TDI is a new modality that measures the velocity of the myocardium during the cardiac cycle  instead of blood flow . TDI velNormally, a systolic part (Vs), an early diastolic part (Ve or E’), and a late diastolic part (Va or A’) can be differentiated. If diastolic function is normal, the peak of Ve tends to be earlier than the peak of the mitral flow E wave. Patients with impaired ventricular relaxation have a Ve/Va ratio less than 1 . Tissue Patients with systolic dysfunction present with left ventricular dilation and a reduced ejection fraction. Left ventricular damage from any cause can initiate and perpetuate a process called left ventricular remodeling. Ultimately this process culminates in an increase of left ventricular enddiastolic and endsystolic volumes, a reduced ejection fraction and an increase of left ventricular wall stress ,39. HearPatients, who have dilated hearts and a reduced left ventricular ejection fraction may occasionally be asymptomatic and can be identified by echocardiographic population screening or screening of plasma brain natriuretic peptide ,42. 3).Measurement with pressure-volume loops is the gold standard for assessment of left ventricular systolic dysfunction . In patients with dilated cardiomyopathy, mitral annular systolic velocities are significantly lower compared to normals and correlate well with left ventricular ejection fraction [Tissue Doppler Myocardial Imaging can be applied for the measurement of longitudinal systolic left ventricular wall motion. (Fig. fraction . Next tofraction .Regional left ventricular function can be calculated with the myocardial velocity gradient or by strain rate imaging . Strain As previously oulined, systolic or diastolic left ventricular dysfunction is difficult to identify solely on the basis of signs and symptoms . The mosThe service has been very succesful in detecting left or right ventricular dysfunction and the etiology of cardiac murmurs. The echocardiogram frequently gives the general practitioner additional information with minor discomfort for the patient. The costs of setting up open access services can be considerable. Therefore there have been concerns about this service . HoweverUntil now the service is has gained only acceptance in the United Kingdom and the Netherlands. The service is cost-effective and can avoid unneccesary referrals to the outpatient clinic of cardiology.Another way to limit the number of referrals is by prescreening of patients by making electrocardiograms or by measurement of plasma BNP . Because


Congestive hepatomegaly might be the first sign for pulmonary hypertension. Apparent diffusion coefficient (ADC) value obtained with quantitative diffusion-weighted magnetic resonance imaging (DW-MRI) is affected by liver fibrosis and perfusion. We aimed to evaluate the diagnostic value of DW-MRI in cooperation with biochemical markers, ultrasonography (US) and echocardiography (TTE) in determining the degree of hepatic congestion secondary to pulmonary hypertension (PHT).35 patients with PHT and 26 control subjects were included in the study. PHT was diagnosed if pulmonary artery systolic pressure (PASP) was measured above 35 mmHg with TTE. Study group was classified into mild and moderate PHT. DW-MRI was performed with b-factors of 0, 500 and 1000 sec/mm². Mean ADC, ADC-II , US, TTE and blood biochemical parameters of both groups were compared.There exists a positive correlation between liver size and the diameters of vena cava inferior, right atrium, right hepatic vein(RHV), mid-hepatic vein(MHV), left hepatic vein(LHV) (p < 0.01). There was a positive correlation between PASP and RHV, MHV, LHV. The patients had lower ejection fractions (p < 0.01) and higher LDH (p < 0.01) and ALP (p < 0.05) levels than the control group. The ADC values of the patients with moderate PASP were higher than those with a mild PASP (p < 0.05). Mean ADC was higher in patients with moderate PHT compared to control group (p = 0.009). There was a positive correlation between PASP and ADC values of right lobe posterior segment of the liver (p < 0.05). The ADC-II and mean ADC values of the patients with moderate PASP were higher than those of the control group (p < 0.01).Congestion due to moderate PHT might be diagnosed with DW-MRI. As PASP increase; mean ADC and ADC-II values increase. Pulmonary artery pressure and pulmonary vascular resistance increases due to the physiopathological and histopathological changes , both of which may be demonstrated with ultrasonography (US), may result from hepatic congestion. However, these signs are observed in advanced PHT cases and hepatomegaly plus intra-abdominal free fluid may be noted with increased severity ,8. SignsThere are several publications indicating the efficacy of quantitative apparent diffusion coefficient (ADC) measurement with diffusion weighted magnetic resonance imaging (DW-MRI) in proving liver fibrosis and evaluating other space occupying lesions . DiffusiIn our prospective study, we aimed to evaluate the diagnostic value of DW-MRI in cooperation with biochemical markers, US and TTE in determining the degree of hepatic congestion secondary to PHT.The study was performed on 61 subjects, consisting of 39 (63.9%) females and 22 (36.1%) males with an age range of 25 to 82, recruited between July 2008 and February 2009. Mean age of the subjects was 53.51 ± 13.98. Written informed consent was obtained from all subjects in conformity with the requirements of local ethics committee. Subjects were divided into two groups as "study group" (n = 35) and "control group" (n = 26). Study group was composed of patients diagnosed with TTE confirmed secondary PHT with underlying diseases such as rheumatic heart disease, chronic obstructive lung disease and congenital heart disease in the etiology. Patients with normal TTE findings were included in the control group. Lack of right heart failure, another systemic disorder or malignity, chronic liver disease and hepatic vascular pathology, acute and chronic hepatic diseases  as revealed by the past medical history, physical examination and laboratory findings were the inclusion criteria of the study applied for both groups. A diagnosis of PHT was established according to pulmonary arterial systolic pressure (PASP) > 35 mmHg recorded by TTE. Diagnosis of PHT was based on from the European Society of Cardıology and the European Respiratory Society Guidelines for the Diagnosis and Treatment of PHT . PatientThe physical examination and evaluation of the patients was performed by a cardiologist and gastroenterologist independently. The history of the patients were particularly assessed concerning orthopnea, paroxysmal nocturnal dyspnea (PND) and effort dyspnea. During cardiac evaluation all minor and major criteria of heart failure like jugular venous pressure (JVP), jugular-venous reflex (JVR), hepatomegaly, and pretibial edema were evaluated. Patients with high JVP, positive JVR, orthopneic and PND patients, patients with congestive and right heart failure or patients under treatment, moderate tricuspid regurgitation and finally patients with critical PHT were excluded from the study. All patients had a full history taken for alcohol use, medications and risk factors for viral hepatitis. Electrocardiography, chest X-ray, echocardiography, aspartat transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total and indirect bilirubin, upper abdominal US and liver DW-MRI were performed in all patients and control group. All patients had afull history taken for alcohol use, medications and risk factors for viral hepatitis.Patients were excluded from the study, if they had acute coronary syndromes, severe functional capacity (NYHA-IV), a diagnosis of or a symptom suggesting chronic liver disease, malignity, any contraindication for MRI, inadequate echocardiographic evaluation, severe PHT and patients with severe tricuspid regurgitation.2) + right atrial pressure) [Two-dimensional continous doppler, color doppler recordings of patients via TTE  with a 2.5 - 3.5 MHz phased-array transducer were provided by an experienced cardiologist, who had no information about the patient's medical history, liver function test, US and MRI findings. TTE was used to measure left ventricular ejection fraction (EF), diameters of right ventricle (RV), right atrium (RA), left heart chambers and tricuspid failure . The diaressure) , (Table ressure) .Abdominal US evaluations of the patient and control groups were performed in supine position subsequent to 6 hours of fasting. GE Logic 9 device  with 3.5-5 mHz convex probe was used for the evaluations with two accompanying radiologists with expertise on abdominal radiology. Craniocaudal  measurements of the liver were performed in the mid-clavicular axis. Diameter of IVC was measured 1 cm above the merging point of hepatic veins, right hepatic vein (RHV), left hepatic vein (LHV), and middle hepatic veins (MHV) were measured from 1 cm to IVC, and portal vein (PV) was measured at the level of hilus of the liver. Liver parenchymal echogenicity was found to be homogenous and normal in all subjects (study and control groups) and space occupying lesions were neglected including cysts and hemangiomas that were smaller than 1 cm.MR imaging was performed on a 1,5 T body scanner  with a 33 mT/m maximum gradient capability using an eight channel phased-array body coil.Before diffusion weighted imaging, breath hold, axial 3D gradient-echo T1-weighted sequence; ; 2D gradient-echo T1 in-phase and out-of-phase , axial respiratory-triggered, turbo spin-echo T2-weighted sequence with fat saturation , coronal T2-weighted half-Fourier single-shot turbo spin-echo (HASTE)  sequences and then diffusion weighted single-shot spin-echo echo-planar sequence with, chemical shift selective fat-suppression technique; TR/TE, 4900/93; matrix, 192 × 192; slice numbers, 30; slice thickness = 6 mm; interslice gap, 35%; FOV, 45 cm; averages, 5; acquisition time, approximately 3 minutes, PAT factor, 2; PAT mode, parallel imaging with modified sensitivity encoding (m SENSE) was performed. DW-MRI was performed with b-factors of 0, 500 and 1000 sec/mm².The DWI datasets were transferred to an independent Workstation  for postprocessing, and the ADC maps were reconstructed.2 in size. Care was taken to exclude vessels and motion artifacts from the ROIs. For each ADC value measurement, we applied three ROIs measurements to each segment and accepted the average.To measure ADC value two abdominal radiologists established round regions of interest (ROI) on the right lobe posterior (RLP) and anterior (RLA) and left lobe medial (LLM) and lateral (LLL) segments in consensus. The ROIs were between 2-4 cmAverage of mean ADC values of the RLA and RLP segments was calculated as ADC-II. Mean ADCs, US, ECHO and blood biochemical parameters of both groups were compared.NCSS 2007 & PAS 2008 Statistical Software  were used for statistical analysis. Complementary statistical methods  as well as student t-test was used in the comparison of quantitative data and parameters with normal distribution. Pearson correlation analysis was used to evaluate the relationship between parameters. Results were evaluated with a 95% confidence interval and p < 0.05 level of significance.Etiological distribution of patients with PHT included 21 cases with rheumatic valve disease, 8 cases with left heart failure and 6 cases with chronic obstructive pulmonary disease. There was no difference between the PHT and control groups in terms of distribution of age and sex (p > 0.05).Levels of LDH  and ALP  of the PHT group were higher than those of the control group.Doppler echocardiographic evaluation of the PHT and control groups showed that mean PASP was lower in patients with normal RA compared to those with enlarged RA (p < 0.05). There was no difference in mean PASP in terms of RV and left atrial (LA) diameters (p > 0.05). EF was markedly lower in the study group compared to the control group .Significant positive correlation and significant association was determined between liver size and diameter of IVC (43.1%), diameter of RA (38.3%), diameter of RHV (41.8%), diameter of MHV (40.5%) and LHV (41.1%) Table .There was no difference in terms of liver size, diameters of VP, IVC, RHV, MHV and LHV between patients with mild PHT and control group (p > 0.05). Mean ADC was higher in patients with moderate PHT compared to those with mild group (p = 0.025) Table . Mean ADMean ADC 1.82 ± 0.16) was higher in patients with moderate PHT compared to those with mild PHT (1.62 ± 0.22) (p = 0.025) Figure , mean AD ± 0.16 wet al., levels of ALP, ALT, bilirubin and GGT were significantly increased in conformity with the level of tricuspid failure [PHT may lead to chronic passive hepatic congestion and ischemic hepatic dysfunction due to secondary right ventricular dysfunction. Increased right heart chamber pressures secondary to physiopathological changes, in pulmonary arteries result in dilatation of IVC and hepatic veins. Stasis in the hepatic sinusoids stem from elevated hepatic vein pressure cause hepatocellular hypoxia and necrosis. These hepatic changes may present clinically as hepatomegaly, ascites, edema and subicterus. Serum bilirubin, transaminase, ALP and prothrombin times may be increased as a result of hepatic dysfunction -18. In o failure . ElevateSensitivity and specificity of PASP measurement with Doppler echocardiography compared to right-heart catheterization are 100% and 96%, respectively ,6.et al. have demonstrated that mortality rates increase in the presence of dilatation and dysfunction of right heart chambers [Several studies, including that of Jayant Nath chambers -25. We aAlthough used commonly in clinical practice, the sensitivity and specificity of US varies in different liver pathologies . A positive correlation was determined between liver size and diameters of IVC, RA, RHV, MHV and LHV Table ; howeverDiffusion-weighted imaging is a new imaging modality recently implemented to be used in abdominal diseases including diffuse liver diseases. This modality takes approximately 3 minutes in addition to a routine abdominal MRI and is a non-invasive procedure, which does not require contrast material injection. Its advantages include application without breath holding, repeatability and relative cheapness. This modality may also be used in the follow up of patients by making quantitative measurements on ADC map constituted from diffusion images -29. DiffAccurate detection and characterization of focal and diffuse hepatic lesions can be performed with MR imaging. Various sequences, such as inversion recovery, gradient echo, spin echo seqıences are highly sensitive for the detection of lesions. Once detected, they can often be accurately characterized as malignant or benign, cyst or solid tumor, etc., based upon their appearance and relative signal intensity on T1- and T2- weighted sequences with the help of fat supression techniques and intravenous contrast material administration. Diffuse liver diseases like fatty infiltration, iron accumulation or fibrosis may be detected with these sequences . HoweverDW-MRI studies aimed at demonstrating liver diseases have shown limited diffusion and decreased ADC value particularly in hepatitis, liver fibrosis and cirrhosis due to reduced intercellular water and fibrotic reactions -28. ReduClinically ultrasonography is used in the evaluation of liver parenchyma and is capable of showing morphological changes resulting from passive congestion particularly in cases with PHT. In our study, changes in liver parenchyma have been demonstrated in patients with moderate PHT using DW-MRI. LDH (p = 0.002) and ALP (p = 0.038) levels of patients with PHT were determined to increase compared with control patients. Although LDH and ALP increase may be noted in several liver pathologies other than hepatic congestion, mean ADC is decreased rather than increased in fibrotic liver parenchymal diseases ,41. The The therapeutic options for PHT have significantly improved in the last few years. But the disease is still too often diagnosed late in its course. In more than 80% of patients the diagnosis is made and treatment started when the condition is already in NYHA class III-IV with a very poor prognosis. According to the EARLY study, beginning treatment 3-6 months earlier can improve prognosis and progression of the PHT . Late diIn our study, the congestion related alterations in USG and DW-MRI investigations were also evident among patients with PTH without symptom and clinically overt heart failure. Identification of significant differences in RLA and RLP in congested liver seems to be the superiority of DW-MRI to USG in evaluation of cardiac congestion. Additionally DW-MRI was shown in our study as a different radiological method enabling detection of cardiac congestion before the development of heart failure. The efficacy of early treatment induction (such as diuretics) in patients with PTH has been a well-known phenomenon as demonstrated by past studies . This maThe limitations of the study: MR is not often available and it is not that cheap. Moreover, these patients are often orthopneic and it may be difficult to perform an MR. However technological advances in the field may overcome at least some of these problems by shortening the examination duration.Consequently, DW-MRI performed to diagnose hepatic congestion secondary to moderate PHT is an easy-to-use, non-invasive and repeatable test that gives quantitative results and may be used in conjunction with routine MRI modalities. In addition, hepatic congestion (with increased ADC) may be easily distinguished from diffuse parenchymal liver diseases characterized with reduced ADC values. Collectively, these data indicate that further studies should be performed to clarify the place of this modality in both cardiac and other congestive liver pathologies.The authors declare that they have no competing interests.YD, AS, OK, TD, KOK collected all data and participated in the design of the study. YD and OK were supervisor of the echocardiographic, and MRI examinations.SND, GAE, NY, SP and KS drafted the manuscript with YS. All authors read and approved the final manuscript.


A myxoma is the most common primary tumor of the heart. It has been reported as the source of a cardiogenic embolism. Therefore, it is important for clinicians to detect the myxoma early via echocardiography to prevent complications, such as syncope, sudden death, and cerebral embolic ischemic stroke. This report presents the case of a 54-year-old female whose clinical manifestation of atrial myxoma was an ischemic stroke. Atrial myxoma was later confirmed as the cause of her symptoms via transesophageal echocardiography. Cerebral infarction induced by cardiogenic embolism is observed in about 20% of stroke patients. Of those patients, atrial fibrillation is responsible for over 50% of the cardiogenic emboli, while myxomas are observed in only 0.5% of emboli . Atrial 1 and S2 heart sounds without murmurs. An EKG showed a normal sinus rhythm. Range of motion was limited to 30° for the left upper and lower extremities. She had 1/5 motor strength on the left side, but 5/5 motor strength on the right side. The deep tendon reflexes were 2+ bilaterally. Her sensation was intact bilaterally. The Babinski and Hoffman signs were both negative. All her laboratory results were normal. A chest X-ray showed a normal cardiac silhouette with no signs of pulmonary edema. A non-contrast computed tomography (CT) scan of the brain revealed multiple low density areas in the right frontal and parietal lobes. Our stroke team started her on intravenous heparin. Metoprolol (Toprol-XL) and furosemide (Lasix) were administered to stabilize her blood pressure. The following day, magnetic resonance imaging (MRI) of the brain demonstrated an acute infarction in the distribution of the right middle cerebral artery . She was alert and oriented, had left facial paralysis, slight dysarthria and right-sided tongue deviation, but no dysphasia. On cardiac examination, the carotid impulse was normal without a bruit. Her heart had a regular rate and rhythm, and there were normal SA myxoma is the most common primary tumor of the heart. Primary cardiac neoplasms are rare, with incidences ranging from 0.001–0.3% in autopsy series. Benign tumors account for 75% of primary neoplasms and malignant tumors account for 25%. Myxomas compromise 30–50% of primary cardiac tumors [Myxomas originate from the mesenchymal cells of the septal endocardium. They are gelatinous with a smooth or lobulated surface and are usually white, yellow, or brown in color. They can present as villous, papillary, sessile, or pedunculated-type growths. Approximately one-half of the cases of myxomas are pedunculated tumors, and these are irregular and more likely to result in emboli because of the mobility of this type of tumor . Sixty tA myxoma may be completely asymptomatic until it grows large enough to obstruct the mitral or tricuspid valve or fragments that give rise to emboli. Because they are intravascular and friable, myxomas account for most cases of tumor emboli . EmbolisThe emboli that occur are either a tumor fragment that is released from the myxoma or a blood clot that is formed on the surface of the myxoma. These resulting emboli can result in infarction, as occurred in our patient. More precisely, it has been reported that 45% of patients with myxomas have neurologic manifestations resulting from embolization . This em2, is representative of a growing medical problem in the United States. With stroke patients, physicians use TTE routinely when they search for cardiogenic embolic sources. But, in using TTE exclusively, myxomas in the obese will frequently be missed.Usually, the diagnosis is readily established by two-dimensional echocardiography, which is considered the gold standard. TEE may be useful when transthoracic findings are equivocal or confusing. MRI has been of value in diagnosis, providing excellent cardiac definition. Cardiac catheterization is not necessary in the majority of cases, but may be necessary when other cardiac disease is suspected or if other diagnostic studies are equivocal. TTE has a sensitivity of 95% and the sensitivity is nearly 100% [This case demonstrates the importance of investigating the possibility of cardiogenic source in stroke, as our patient developed cerebral infarction that was caused by an atrial myxoma. It is important that clinicians consider using echocardiography in stroke patients. Treating the atrial myxoma can prevent a cardioembolic stroke and its complications. In conclusion, TEE, as compared to TTE, has many more advantages when physicians search for a cardiogenic embolic source in obese stroke patients. In addition, because obesity has sharply increased in the United States, the importance and use of TEE will increase over time as physicians encounter obese patients with cardiogenic emboli.MCA: Middle Cerebral ArteryP; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; TEE: Transesophageal Echocardiography; TTE: Transthoracic Echocardiography.The authors declare that they have no competing interests.MY and DG were involved in the clinical assessment and writing the case report. All authors read and approved the final manuscript.Full written consent was received for the manuscript to be published.


In 1981 de Bold et al. reported that the injection of atrial tissue extracts in rats induced natriuresis, a discovery that initiated a flurry of research leading to the discovery of a new class of cardiac hormones, the natriuretic peptides.The family of natriuretic peptides consists of several tightly-related members: atrial natriuretic peptide, B-type (formerly ‘brain’) natriuretic peptide, C-type natriuretic peptide and dendroaspis natriuretic peptide.Atrial natriuretic peptide (ANP) is primarily produced in both atria; production and release of ANP is typically triggered by increased atrial-wall tension typically following an increase of intravascular volume or pressure. The ventricles of normal adults produce only small amounts of ANP, but this production is enhanced in the ventricular tissue of fetuses/neonates and in hypertrophied ventricles.8B-type natriuretic peptide (BNP), originally identified in the porcine brain, is found wherever myocardium is present, but is particularly concentrated in the cardiac ventricles. BNP and its cleavage equivalent NT-proBNP have emerged as superior markers for left-ventricular dysfunction, because when cardiomyocytes are stretched, these peptides are rapidly expressed at gene level and immediately released into the circulation. Importantly and in contrast to ANP, these peptides are also more stable,C-type natriuretic peptide (CNP) has two forms, which are both products from a different cleavage process of a pro-CNP precursor. CNP predominates in the vascular endothelial cells, the central nervous system, the kidney and the pituitary gland. Plasma-concentration is low but tissue expression is high, suggesting a paracrine role for CNP.13108. This proBNP108 is enzymatically cleaved immediately in a 1:1 ratio to yield BNP (32 amino acids) and NT-proBNP (76 amino acids) which are directly released into the circulation.108 is measured in the circulation as well.108 is known to be detected by all BNP and NT-proBNP assays, whether glycosylated proBNP108 has any effect on conventional assays for natriuretic peptides is still not known.When cardiomyocytes are stretched, as in cardiac chamber overfilling, the BNP gene is quickly up-regulated, which leads to a rapid intracellular production of a 134 pre-pro-peptide. This pre-pro-peptide is rapidly cleaved to a 108 pro-peptide, proBNPWhile NT-proBNP is thought to be inert without any physiological function, BNP is biologically active and is responsible for several compensatory mechanisms in HF such as an increase of urine production and sodium excretion, a decrease of the aldosterone level, a lowering of the blood pressure and a lowering of the pulmonary capillary wedge pressure.22108, but not with other BNP fragments.Importantly, the clearance of the two peptides is different: BNP is cleared by several mechanisms, including the kidneys, specific clearance receptor-mediated degradation  and catalytic degradation via enzymes, especially neutral endopeptidase 24.11,Despite the potential differences and analytical concerns, recent head-to-head comparisons show that BNP correlates as well as NT-proBNP with clinical variables in patients with HF, indicating that most of the results of the BNP and NT-proBNP studies are generally transposable.31In the Emergency Department (ED), it is important to quickly diagnose the primary cause of acute dyspnea, since the success of most treatment therapies depends on the time-interval between presentation and treatment. Physicians therefore need a tool which is quickly available and adequately diagnoses or excludes HF. Although echocardiography can be performed quickly, it has to be carried out by an experienced person. Besides that, there is discussion what should be the echocardiographic gold standard for the diagnosis of diastolic HF.33Smaller studies already had suggested that NT-proBNP was such a beneficial diagnostic tool in acute dyspnea.36exclusion of acute HF, a general age-independent cut-point of 300 pg/mL should be used, while for diagnosis of HF, age-dependent cut-points were more useful than a single cut-point: namely NT-proBNP > 450 pg/ml for patients < 50 years, > 900 pg/ml for patients in between 50 and 75 years, and NT-proBNP > 1800 for patients > 75 years.  Study.5 years. This age-stratified approach was superior to using a single NT-proBNP cut-point; both were equally sensitive and specific, but by stratifying age, the positive predictive value of the marker increased significantly, speaking to the strong relationship between age and structural/functional physiologic changes with effects on natriuretic peptide values. Such an age-related effect on natriuretic peptides is by no means restricted to NT-proBNP; recent data suggest age is the most potent variable leading to an elevated BNP value in the absence of acute HF, with a 30% increase in the likelihood for a “false positive” BNP per decade of age.Despite important improvements the last decade in the treatment of HF such as the introduction of beta-blockers or implantable defibrillators,Valvular heart disease is a common cause of HF, either by leading to volume overload  or by causing pressure overload (e.g. aortic stenosis), and these relationships are frequently reflected in changes of NT-proBNP values. Since the clinical tools typically utilized to time the moment of intervention for valve repair or replacement are frequently limited to clinical judgment, an objective measure to guide the timing for intervention would be welcome, particularly since for instance recovery of LVEF or regression of LV mass is all but guaranteed after well-timed aortic valve replacement for aortic stenosis.As an example, several studies have shown that NT-proBNP indeed correlates not only with onset and severity of symptoms but also with prognosis in aortic stenosis.65While most of these studies predict a promising role for NT-proBNP in valvular heart disease management, further research is warranted in order to establish the role of NT-proBNP in a decision algorithm for valvular heart disease.Patients with obstructive airway disease represent a particular challenge in the emergency department setting, as symptoms and signs of pulmonary disease may mimic (or mask) those of HF. Thus, the natriuretic peptides are a welcome advance for the correct identification of HF in patients with prior lung disease. In a recent study, Tung and colleagues have shown in 216 patients with underlying chronic obstructive pulmonary disease (COPD), that NT-proBNP was very useful for correctly identifying or excluding acute HF in this challenging patient population, superior to clinical judgment for this indication.An important consideration in patients with pulmonary disease is involvement of the right ventricle as a consequence of their pulmonary disease: since NT-proBNP is produced everywhere cardiomyocytes are present it is well known that cardiomyocytes in the right ventricle produce NT-proBNP to a meaningful degree, particularly when stretched.In addition to acute right ventricular overload, NT-proBNP concentrations are also elevated in chronic PAH. Fijalkowska and colleagues demonstrated that NT-proBNP concentrations were not only increased in patients suffering from PAH, but also predicted 3-year death. Importantly, a high long-term mortality rate (61%) was observed in patients in whom plasma NT-proBNP levels increased by at least 50% during the follow-up period, while the mortality rate was significantly lower among other patients .72An interesting study was performed by Goetze et al. in a population of patients evaluated for lung transplantation. While the patients with terminal parenchymal pulmonary diseases and normal LVEF had normal NT-proBNP concentrations , patients with primary PAH had significantly higher NT-proBNP concentrations .73One important population where a marker for HF would be incrementally useful is in the obese patient. These patients do often have complaints of dyspnea but clinical parameters  and technical investigations (chest X-ray and echocardiography) to make a diagnosis of HF are more difficult to interpret. Especially since both the prevalence of HF and obesity are increasing in our modern society, a sensitive marker for HF in the obese population would be most welcome.74Surprisingly, HF patients with a higher body-mass index (BMI) have a better prognosis than patients with a normal BMI, the so-called ‘Obesity-paradox.’84An important study in this perspective was performed by Krauser and colleagues.The obvious ramifications of these data include this possibility of an obesity-related neurohormonal ‘suppression’ effect, such that the most obese patients may have a ‘handicap’ in their ability to secrete natriuretic peptides, and as such might be rendered more susceptible to hypertension, volume retention, and perhaps HF. As well, the interpretation of both BNP and NT-proBNP may be hindered by higher BMI; whether it interferes with the prognostic value of the markers remained unclear. However, recent data from the ICON study group have shown that despite a decreased production of NT-proBNP in obese subjects, NT-proBNP keeps its diagnostic capabilities across all BMI categories. .Despite all the recent experience with NT-proBNP testing, there is still some debate how to interpret NT-proBNP concentrations in patients with renal impairment, since there is a inverse correlation between NT-proBNP and glomerular filtration rate (GFR).Considering the effects on renal disease and natriuretic peptides, certain very important concepts must be kept in mind. First, it is presumed that although steric and electrostatic factors also play a role in glomerular filtration, all molecules weighing less than 50 kDa should pass the glomerulus freely.992). While both NT-proBNP > 4647 pg/ml and GFR <60 ml/min/1.73m2 were independent predictors of outcome , the combination of a GFR<60ml/min/1.73m2 with a NT-proBNP >4647 pg/ml was the best predictor of 60 day mortality . Among subjects with a NT-proBNP above the median, those with a GFR <60 ml/min/1.73m2 had the worst prognosis while in subjects with a NT-proBNP below the median, prognosis was not influenced impaired renal function at presentation. , myocardial wall stress increases, and variable reductions in LVEF may also occur, the possible role of NT-proBNP testing for evaluation of ischemic heart disease has also been studied.110These findings did not perfectly fit in the concept that NT-proBNP is merely a marker of acute myocardial stretch and suggest another mechanism. Firstly, NT-proBNP is associated with older age, hypertension, renal impairment, diabetes mellitus and pre-existent left ventricular dysfunction, which are also predictors of worse outcome. It might therefore be that NT-proBNP results “sum” up all these parameters, and represent a “final common pathway” marker for prognosis. However, when corrected for these factors in multivariate analysis, NT-proBNP remains an independent predictor.NT-proBNP has now become an established marker in modern medicine, thanks to the broad array of data supporting its role in a number of disease states, most notably being HF. The results of NT-proBNP testing are quickly available and have a high diagnostic value, even superior to single clinical parameters and chest X-ray. This diagnostic accuracy remains also in the presence of moderate renal impairment, underlying pulmonary disease or obesity. Besides its high diagnostic value, it is more important to realize that NT-proBNP is also a most strong predictor of prognosis, not only in HF, but also in valvular heart diseases, pulmonary hypertension, and ACS. Thus, while troponins are necrosis markers and could be considered ‘the epitaph’ of the cardiomyocyte, NT-proBNP should be considered an ‘S.O.S. signal,’ which indicates that the cardiomyocyte is distress and some kind of intervention is needed.The future of NT-proBNP testing is bright: at present numerous studies are examining the role of NT-proBNP testing for “screening” of apparently well patients in primary are offices for incipient HF, while the role of NT-proBNP testing for the monitoring and titration of outpatient HF therapy is also under close examination.


The inherent ability of ventricular myocardium to increase its force of contraction in response to an increase in contraction frequency is known as the cardiac force-frequency relation (FFR). This relation can be easily obtained in the stress echo lab, where the force is computed as the systolic pressure/end-systolic volume index ratio, and measured for increasing heart rates during stress. Ideally, the noninvasive, imaging independent, objective assessment of FFR would greatly enhance its practical appeal.1 – To evaluate the feasibility of the cardiac force measurement by a precordial cutaneous sensor. 2 – To build the curve of force variation as a function of the heart rate. 3 – To compare the standard stress echo results vs. this sensor operator-independent built FFR.The transcutaneous force sensor was positioned in the precordial region in 88 consecutive patients referred for exercise, dipyridamole, or pacing stress. The force was measured as the myocardial vibrations amplitude in the isovolumic contraction period. FFR was computed as the curve of force variation as a function of heart rate. Standard echocardiographic FFR measurements were performed.-3 . Sensor built FFR slope and shape mirror pressure/volume relation during stress. This approach is extendable to daily physiological exercise and could be potentially attractive in home monitoring systems.A consistent FFR was obtained in all patients. Both the sensor built and the echo built FFR identifiy pts with normal or abnormal contractile reserve. The best cut-off value of the sensor built FFR was 15.5 g * 10 This inherent ability of ventricular myocardium to increase its force of contraction in response to an increase in contraction frequency is known as the cardiac force-frequency relation (FFR) [The frequency-dependent control of transmembrane Caeostasis . An incron (FFR) -6. Amongon (FFR) ,8. Echocon (FFR) -13. It ion (FFR)   referred for stress echocardiography . The type of stress was clinically driven for exercise vs. dipyridamole, and by the presence of a permanent pace maker for pacing stress. The characteristics of the study patients are reported in Table All patients met the following inclusion criteria: 1) referred to stress echo for clinically-driven testing; 2) acoustic window of acceptable quality; 3) willingness to enter the study. Exclusion criteria were: 1) unstable angina or recent myocardial infarction; 2) moderate-to-severe aortic stenosis; 3) hemodynamic instability, documentation of life-threatening ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation), atrial fibrillation. From the initially considered population of 92 patients, 4 were excluded for poor acoustic window (n = 2), or refusal to give written informed consent (n = 2).Graded bicycle semi-supine exercise echo was performed in 49 patients starting at an initial workload of 25 watts lasting for 2 minutes; thereafter the workload was increased stepwise by 25 watts at 2 minutes interval. A 12-lead electrocardiogram and blood pressure determination were performed at baseline and every minute thereafter .Dipyridamole stress echo was performed following the protocol of American Society of Echocardiography ,17, usinContraindications of using dipyridamole were asthma, hypotension, bradyarrhythmias.The study population consisted of 8 patients with a permanent pace maker. The pacing protocol was accelerated (with a 10-beat increment every 60 s) until one of the following criteria was reached: 1 – 85% of maximal heart rate ; or 2 – PM maximal programmable heart rate . Stimulation was performed, wherever possible, in atrial stimulation mode, or dual-chamber (DDD) pacing to have normal contraction sequence. In the VVI-implanted patients, ventricular stimulation mode was used [The diagnostic end-points for all types of stress were: the development of obvious echocardiography positivity, obvious alterations of ECG (ST segment shift >3 mm). The exam was also stopped in case of limiting subjective side effects or hypertension , hypotension (relative or absolute) with decrease of the blood pressure >30 mmHg, supraventricular arrhythmias , ventricular arrhythmias ; limiting dyspnoea, or maximal predicted heart rate in the absence of ischemia .All patients underwent transthoracic echocardiography at baseline and during stress.Left ventricular end-diastolic and end-systolic volumes were measured from apical four- and two-chamber view, by an experienced observer using the biplane Simpson-method . Only reThe Wall Motion Score Index (WMSI) was calculated in each patient at baseline and peak stress, according to the recommendations of the American Society of Echocardiography from 1 = normal-hyperkinetic to 4 = dyskinetic in a 17 segment model of the left ventricle ,19.One nurse recorded blood pressures at rest and during each individual study. The blood pressure recording was made using a sphygmomanometer and the diaphragm of a standard stethoscope. Systolic and diastolic blood pressure was obtained in the right arm. During exercise test, blood pressure recording was obtained with patient lying in a left rotated semi supine position and instructed to hand grip to the left support with their left hand. Patients have been told to let their right hand go limp when blood pressure was measured.In order to build the force-frequency relation, the force was determined at each step as the ratio of the systolic pressure (cuff sphygmomanometer)/end-systolic volume index (biplane Simpson rule/body surface area). At each heart rate step three cardiac cycles were analyzed and the ESV was calculated as the mean value. The FFR was built off line. The slope of the relationship was calculated as the SP/ESV (Systolic Pressure/End-Systolic Volume) index increase (Δ SP/ESV index from baseline to peak stress) Figure . The FFRIn all, ventricular arterial coupling was indexed by the ratio of left ventricular systolic elastance index (systolic pressure/end-systolic volume index) to arterial elastance . Echocardiography (for ESV and stroke volume) and cuff sphygmomanometer  provided the raw measurements.Because stroke volume (and input impedance) varies directly with body size, arterial elastance was adjusted for body surface area (EaI) to better reflect differences in arterial properties with age and between the genders adjusted for differences in body size ,21. Of nSVR were calculated according to the traditional formula:where 5 is an approximation of the right atrial pressure and MAP is mean arterial pressure.Systemic arterial compliance (C) was calculated as stroke volume index/systemic arterial pulse pressure; where pulse pressure = systolic blood pressure - diastolic blood pressure .Isovolumic myocardium contractions generate vibrations which have audible components that are responsible for the first heart sound ,8. These2) with a resolution of 0.0005·g. We housed the device in a small case . The device includes in one single package a MEMS sensor that measures a capacitance variation in response to movement or inclination and a factory trimmed interface chip that converts the capacitance variations into analog signal proportional to the motion. The device has a full scale of ±2·g , at each incremental stress test, at peak test, and during recovery. Baseline, peak stress, peak-rest difference as absolute value, and delta % rest-peak stress values were computed. The force-frequency relation was defined up-sloping when the peak stress force was higher than baseline and intermediate stress values; biphasic, with an initial up-sloping followed by a later down-sloping trend, when the peak stress force was lower than intermediate stress values; flat or negative, when the peak stress force was equal to or lower than baseline stress values ,14. The SPSS 11 for Windows was utilized for statistical analysis. The statistical analyses included descriptive statistics . Pearson chi-square with Fisher's exact test for categorical variables and the Mann-Whitney test for continuous variables for inter-group comparisons were performed to confirm significance .The one-way ANOVA was used to compare continuous variables between groups; when homogeneity of variance was not present, the Kruskal-Wallis test for nonparametric independent samples was used. Intergroup comparison was performed with Scheffe and Tamhane post hoc tests, respectively.Relations between variables were assessed using linear regression analysis and Pearson's correlation coefficient.Analysis of variance with Fisher's post hoc pair wise multiple comparisons was used to assess the significance of intragroup repeated measures. The best predictors of the sensor built force-frequency relation slope and shape were assessed. Receiver operator characteristic (ROC) curve analysis was used to determine potentially useful threshold values of the sensor built FFR as cut-off for normal vs. abnormal contractile reserve . Contingency tables were constructed to assess the sensitivity and the specificity of the new operator independent method to assess the normal threshold for contractile reserve.Technically adequate images were obtained in all patients at baseline (by selection) and during stress.Heart rate was lower in the dipyridamole than in the exercise and pacing groups. The mean ejection fraction increased in the exercise and Dip groups, while decreased in the pacing group. Regional wall motion abnormalities occurred in 4 patients of the exercise, 1 patient of Dip and 2 patients of the pacing groups  group, although the response was heterogeneous at the individual level (Table 2) an abnormal flat or flat-biphasic  force-frequency relationship is shown in Figure SP/ESV index increased to 14.7 ± 8 mmHg/mL/m2; abnormal = Δ SP/ESV index, rest-peak, <0 mmHg/mL/m2) due to the lower stress heart rate increase and to the milder catecholamine increase .A consistent isovolumic systolic force signal was obtained in all patients at rest and during stress Fig. , 5. In tA typical isovolumic systolic force trend during exercise, pacing and dipyridamole stress is shown in Figure -3 in the exercise, from 12.3 ± 6.1 to 15.3 ± 8.1 g * 10-3 in the dipyridamole group, and from 9.5 ± 4.5 to 15.2 ± 5.6 g * 10-3 in the pacing group.The force increased from 10 ± 4.7 to 36 ± 18.7 g * 10Mean force percentage increase was + 275% in the exercise patients, + 28% in the dipyridamole patients and +74% in the eight pacing patients (p < 0.05 between groups) .In the exercise group the Δ rest-peak force was greater in the 9 control subjects than in the 40 patients .Correlations between SP/ESV index changes and force changes are displayed in Figure -3 .The best cut-off value for normal vs. abnormal contractile reserve at dipyridamole stress was Δ isovolumic systolic force = 0.35 g * 10-3). Cardiac vibrations propagate as mechanical shear waves, and the intervening viscoelastic thoracic tissue attenuates the higher frequencies and introduces a variable propagation delay [A stable, reproducible, and consistent isovolumic systolic force signal was obtained in all patients. This high amplitude vibration is an expression of the tension wave front produced during initial activation of the heart in the isovolumic contraction phase . Baselinon delay ,27. The on delay , studiedon delay  demonstrHowever, to our knowledge, this is the first work in which the isovolumic systolic myocardial force vibration was utilized to build the force-frequency relation and in which, for the first time, a comparison with the echo built FFR has been made . Since FExercise evaluates the effect of heart rate increase and inotropic reserve due to adrenergic stimulation during exercise, rather than pure heart rate effect ,29,30.The basic property of the force-frequency effect to progressively enhance myocardial contractility as heart rate increases is augmented at each level of increasing adrenergic stimulation as occurs in exercise by catecholamine spillover. The sensor built FFR fulfilled recording of this typical pattern, both as absolute values, and for the capability to distinguish normal vs. abnormal contractile reserve, as confirmed by the standard echo built FFR cut-off Figure .Dipyridamole has the well known coronary vasodilator effects mediated by the inhibition of adenosine cellular transport, eventually leading to extra cellular adenosine accumulation and steal phenomena . There iThe assessment of force-frequency relationship is a theoretically robust approach for evaluating left ventricular contractility, which has been deployed clinically using invasive, complex and technically demanding methods -6. PreviIn diseased hearts the force-frequency relation is altered. As the heart fails, there is a change in the gene expression from the normal adult pattern to that of fetal life with an inversion of the normal positive slope of the force-frequency relation: systolic calcium release and diastolic calcium reuptake process is lowered at the basal state and, instead of accelerating for increasing heart rates, slows down . The forThe patient's number and the incoming disease were different in the exercise, dipyridamole and pacing stress groups. Controls were present only in the exercise group: it isn't possible to have physiological and hemodynamic comparisons between stress groups. However, aim of this study, was not to assess physiological patterns and differences between type of stress, that are well known, but simply assess the feasibility of sensor isovolumic contraction force recording during stress echocardiography, and to compare the standard operator-dependent echo vs. this sensor operator-independent built force-frequency relation during stress.Because only non-invasive measurements were available, systolic cuff pressure was used as a surrogate for end-systolic pressure. The non-invasive results tend to overestimate the actual ratio, in large part because the brachial arterial pressure reflects an amplified LV pressure wave secondary to the rheological properties of the arterial tree, and this difference may lead to overestimation of left ventricular pressure, specially if younger subjects are studied, in which blood pressure tends to be overestimated . However0 = 0. The volume axis intercept of the end-systolic pressure/volume relationship V0 is generally lower in normal subjects than in CHF patients, and may also differ among DCM patients. Nevertheless, SP/ESV index is generally considered as a valid approximation of LV end systolic elastance [0 changes. It has been reported that V0 is not appreciably altered by inotropic stimulation [0 changed by only 5 mL on average in response to changes in peripheral vascular resistances of 50 to 200% of normal; Little and Cheng [0 during treadmill exercise in dogs. It is likely, however, that V0 changes during exercise but this is impossible to assess at such levels of exercise in man.The estimation of the LV systolic elastance index by SP/ESV index assumes Vlastance . This mamulation  or changmulation  showed tnd Cheng  observedSince end-systolic elastance (Ees), expressing the slope of the in-vivo, end-systolic ventricular pressure vs chamber volume relation, is the most "foolproof" window into in vivo myocardial contractility, Ees should be measured at each heart rate step increase, as made by Liu and coworkers . But meaMedication differences may have had an impact, blunting the force-frequency relation and the diastolic blood pressure. However, this variable could not be controlled for ethical and practical reasons. In addition, the index is relatively independent of afterload changes, since for a given level of contractility – blood pressure reduction should be accompanied by smaller end-systolic volume values.Force-frequency recording is feasible with single precordial vibrations sensor connected to a standard ECG monitoring electrode and quantitatively documents left ventricular contractility changes in a totally automatic, operator independent fashion.Sensor built force-frequency relation is strictly related to the standard stress echo built FFR. Echocardiography uses artificially generated cardiac reflections. The isovolumic systolic force sensor simply records naturally generated heart vibrations. The FFR is built on line. The system is portable, and the remote transmission of the FFR slope and shape is feasible and simple.To establish fully the advantages and limits of this new method, comparisons with left ventricular pressure-volume loops in humans and multicenter study data are needed.C = systemic arterial complianceCO = cardiac outputDCM = dilated cardiomyopathyDC = dilated ischemic cardiomyopathyEaI = effective arterial elastance indexEF = ejection fractionEDV = end-diastolic volumeESV = end-systolic volumeFFR = force-frequency relation2)g = acceleration unit (9.8 m/secHR = heart rateLV = left ventricle/ventricularSP = systolic pressureSVR = systemic vascular resistanceT.B. conceived this study, performed the data analysis, and drafted the manuscript; L.V., C.P., E.Pa., L.P. and M.P. were responsible for data collection and revised the manuscript; V.G., E.B., F.F. and M.G. were responsible for technology development and digital signal processing ; E.Pi. gave a contribution to preparation of study design, data discussion, and critical revision of the manuscript.


Ultrasound speckle tracking from grey scale images allows the assessment of regional strain derived from 2D regardless of angle intonation, and it is highly reproducible. The study aimed to evaluate regional left ventricular functional reserve in elite soccer players.50 subjects (25 elite athletes and 25 sedentary controls), aged 26 ± 3.5, were submitted to an echo exam, at rest and after the Hand Grip (HG) test. Both standard echo parameters and strain were evaluated.Ejection fraction was similar in athletes and controls both at rest (athletes 58 ± 2 vs controls 57 ± 4 p ns) and after HG (athletes 60 ± 2 vs controls 58 ± 3 p ns). Basal  segments showed similar strain values in athletes and controls both at rest  and after HG . Medium-apical segments showed similar strain values at rest , but higher values in athletes after HG In athletes with physiological myocardial hypertrophy, a brief isometric effort produces enhancement of the strain in medium-apical left ventricular segments, suggesting the presence of a higher regional function reserve which can be elicited with an inotropic challenge and suitable methods of radial function quantification such as 2D-derived strain. Regional myocardial function is currently evaluated by with 2D echocardiography in the four-chamber view at rest In athletes, where ischemia is an uncommon event, the main information on myocardial performance is related to global contractility, normally expressed by left ventricular Ejection Fraction (EF),4.Traditionally, a 2D echocardiographic exam is used in the four-chamber view for analysing the motion of the segments in the LV near the apex ; howeverThe segmental contributions of myocardial systolic function can be evaluated using non-invasive quantification of myocardial strain . Strain For reasons of homogeneity, all the subjects studied were men. Twenty-five elite soccer players  aged 26 ± 3.5, regularly trained for two hours at approximately 80% of heart rate five days a week for 10 months a year for 5 years or more, and played one game a week during the regular season. All were matched for age, weight and body surface with 25 controls who perform occasional sporting activity  stress. The subject held the dynamometer in one hand, squeezing the handle at 30% of their previously-established maximal grip strength for 3 minutes. The choice of employing a short, acute effort such as HG was made in order to create pressure load enhancement in the left ventricle chamber and thus in the deformation of the myocardial wall.At rest and at the end of the HG test, heart rate (HR), systolic and diastolic blood pressure  and standard systolic and diastolic echocardiographic parameters were measured. HG was considered efficient if the mean systolic and diastolic pressure values increased significantly during handgrip as compared to the resting state (p < 0.05).2), [Echographic exams were performed at rest and during HG with MyLab 50  equipped with a 2.5 MHz transducer. In accordance with guidelines , the tra2),  and EjecThis software employs the speckle tracking method to automatically evaluate myocardial dynamic properties from two-dimensional B-mode echocardiographic clips ,8,10 Fi.The software, based on a grey scale and without any angle dependence, offers the possibility of detecting strain in the basal and medium-apical segments of the left ventricle myocardial walls. Frame rate was kept between 50 and 80 Hz to optimise the application of speckle tracking for calculating Longitudinal Peak Systolic Strain (LPSS %), and LV (cm/sec) in left ventricle basal and medium-apical segments. We considered the LPSS and the LV values as the means of the values obtained at the basal segments of the interventricular septum and lateral wall and medium-apical sections of the same regions Fig , 2.Data is presented as means ± standard deviation. The comparisons between athletes and controls at rest and at peak stress were performed with Student's two-tailed unpaired test (p < 0.05), while the comparison between basal (resting) state and Hand Grip for each group was performed with Student's paired "t" test. Statistical and power analysis were performed using Statview and STATA Stata – Corp 2003 software.2 athletes vs 92.100 g/m2 controls with p < 0.05 Table Basal -20.99, CMI 101.54, R = 0.09, LPSS Medium-Apical -24.47, CMI 101.54, R = 0,13).All the subjects were healthy, with no statistically significant differences among the general parameters Table . In bothInterest has recently grown ,13 in evIn athletes, where a major curvature of the walls is present ,4 as a cThis investigation, aimed to evaluate, using LPSS, the contribution of the regional contractility of left ventricle medium-apical segments to overall heart performance in the athlete with physiological myocardial hypertrophy.The results demonstrate the applicability of the new speckle tracking method to the calculation of strain in all sections of the heart, also in the medium -apical segments, with results which come within the normal and validated range  A particThese results point to the importance of considering myocardial deformation parameters in LV segments adjacent to the apex, particularly in athletes where regular training produces increased myocardial contractility. We must remember that the actual performance of the apical segments is not correctly assessable with standard 2D; also the current application of the method of strain estimation by TDI is normally limited to basal and medial wall regions due to its angle dependence.In this study, the measurements of myocardial fibre velocity values in the same segments where strain was determined were made with the speckle tracking method, thus overcoming the limitations of aligning the beam with the scan line.Our results show a physiological gradient with a decrease in values from basal to apical segments in the two groups, confirming the literature dataIn conclusion, the significant increase in LV longitudinal strain in athletes suggests the importance of evaluating deformation parameters in order to more thoroughly assess those morphological and functional modifications in the heart which cannot be discovered by traditional echo measurements.In agreement with the normal values recently reported in the literature , these rIn athletes, this evaluation might be extended in future to the investigation of the strain of the two ventricles contracting in real time, in order to determine a the different behaviour of value of these two chambers that normally work at different load pressures.This investigation was performed in athletes with high-quality myocardial echo-images and no further information is available about the possibility of obtaining the same results with high reproducibility in other conditions where image resolution is poor. The endocardial border needs to be optimal, with a clear delineation of the myocardial tissue and extracardiac structures.We must also remember that myocardial contractility is a complex mechanism, recently addressed with new sophisticated software evaluating all components of wall deformation, like radial strain and torsion. In this study the evaluation of the deformation of segments around the myocardial apex, which is normally difficult from the standard 2D echocardiographic four-chamber view can howeAlthough the contribution of the contractility of left ventricle medium apical segments was found to be higher than in the basal ones in soccer players submitted to an HG test, no more information about the impact of a different kind of effort, different sport or different training level is yet available. For this reason, this study must be considered as a partial investigation, which however signals the usefulness of further studies to complete performance evaluation in the athlete's heartThe author(s) declare that they have no competing interests.The initial concept of the study was of GG and LS, who designed the study. LS, GP, LT performed all the measurements and statistical analyses. LS wrote the manuscript and all the authors contributed to, read, and approved the final version.