Patients with a myocardial bridge (MB) and no significant obstructive coronary artery disease (CAD) may experience angina presumably from ischemia, but noninvasive assessment has been limited and the underlying mechanism poorly understood. This study seeks to correlate a novel exercise echocardiography (EE) finding for MBs with invasive structural and hemodynamic measurements.Eighteen patients with angina and an EE pattern of focal end‐systolic to early‐diastolic buckling in the septum with apical sparing were prospectively enrolled for invasive assessment. This included coronary angiography, left anterior descending artery (LAD) intravascular ultrasound (IVUS), and intracoronary pressure and Doppler measurements at rest and during dobutamine stress. All patients were found to have an LAD MB on IVUS. The ratios of diastolic intracoronary pressure divided by aortic pressure at rest (Pd/Pa) and during dobutamine stress  and peak Doppler flow velocity recordings at rest and with stress were successfully performed in 14 patients. All had abnormal dFFR (≤0.75) at stress within the bridge, distally or in both positions, and on average showed a more than doubling in peak Doppler flow velocity inside the MB at stress. Seventy‐five percent of patients had normalization of dFFR distal to the MB, with partial pressure recovery and a decrease in peak Doppler flow velocity.A distinctive septal wall motion abnormality with apical sparing on EE is associated with a documented MB by IVUS and a decreased dFFR. We posit that the septal wall motion abnormality on EE is due to dynamic ischemia local to the compressed segment of the LAD from the increase in velocity and decrease in perfusion pressure, consistent with the Venturi effect. Tsujita et al8 found MBs in 23% of a group of 331 patients, all of whom underwent IVUS, as compared to 3% when using CA alone. Cardiac computed tomography (CT) is a promising noninvasive alternative with accuracy approaching that of IVUS.9 Nevertheless, a noninvasive functional test for clinically significant MBs would be valuable. Nuclear stress testing is not sensitive10 and the reported usefulness of exercise echocardiography (EE) in the detection of ischemia in MBs is near absent from the literature.Identifying MBs among patients with angina is problematic. Historically, MBs have been found by coronary angiography (CA). However, the sensitivity of CA is very low (0.5% to 2.5%).11One challenge to functional testing is that the pathophysiology of how MBs can cause ischemia is poorly understood. There is the belief that MBs should not cause ischemia as they primarily affect only systolic and not diastolic flow. However, at high heart rates, diastole shortens and the systolic contribution to coronary blood flow increases. Also, the assumption has been that the compression of the MB during systole into diastole would have to limit blood flow distal to the MB during diastole to cause ischemia. Yet, in 12 symptomatic patients who were otherwise normal apart from harboring MBs, diastolic fractional flow reserve (dFFR) measured distal to the MB under dobutamine stress was <0.75 in only 5 patients.In this study, we describe a novel EE finding involving a focal abnormality in the end‐systolic to early‐diastolic septal wall motion with apical sparing. We initially had observed the mid‐septal buckling on exercise echocardiography in routine clinical care, with anecdotal cases of finding LAD MBs during follow‐up coronary angiography. We hypothesized that the focal EE finding represented ischemia caused by MBs under stress localized to the bridge.To test our hypothesis we prospectively evaluated a cohort of patients with the EE finding using IVUS , and both intracoronary Doppler and pressure measurements during dobutamine stress, to quantify hemodynamic changes. The presence anatomically of an MB by IVUS and an abnormal dFFR within the MB would corroborate the echocardiographic finding and enhance our understanding of the potential role of MBs in patients with angina.All patients who underwent EE in the Stanford Hospital Echocardiography Laboratory between April 2011 and March 2012 were considered for this study. Patients with late‐systolic/early‐diastolic buckling of the septum with apical sparing on EE (details given below) and symptoms of moderate‐to‐severe angina—either typical or atypical—were prospectively enrolled in the invasive study. Patients with acute coronary syndrome or previously known MBs were excluded because our aim was to conduct a prospective evaluation of the EE finding. All patients gave informed consent. The study was approved by Stanford University Institutional Review Board.In routine clinical care, we had previously noticed a characteristic EE wall motion abnormality associated with MBs of the LAD, as detected by CA. During the end‐systolic to early‐diastolic phase, we identified a focal buckling of the septum with apical sparing . These f12 test with a goal of reaching a target heart rate of 85% of maximal predicted for age. A 12‐lead ECG was obtained at baseline and during the test.EE was performed according to laboratory standards, using an iE33 Ultrasound system . An average of 5 to 10 beats per loop was recorded at rest and post stress. Images were obtained in the parasternal long and short axis, apical 2‐, 4‐, and 3‐chamber views and analyzed on an offline Xcelera work station at normal speed, in slow motion and frame‐by‐frame by a senior echocardiographer (I.S.). All patients performed the Bruce treadmill protocol13Oral negative chronotropic agents were discontinued 2 days prior to the procedure. Baseline CA was obtained before and after 200 μg of intracoronary (IC) nitroglycerine (NTG), in multiple standard views, using the Advantx fluoroscopy system  with acquisitions made at 15 frames per second. IC NTG was administrated to make the bridge more apparent angiographically.IVUS was performed with a 40‐MHz mechanical transducer ultrasound catheter  in the LAD with placement of the IVUS sensor as far distally as possible in the vessel. Both automatic and manual pullbacks were performed.8 The echo lucent half‐moon sign was identified during live recording, whereas percent systolic compression was done offline. Only those patients with an echo lucent half‐moon sign underwent the dobutamine stress protocol. Patients without the IVUS echo‐lucent half‐moon sign were not studied with dobutamine as the procedural delay to allow offline analysis for MB confirmation could not be justified ethically for this study.The presence of an MB was defined by IVUS, either by the identification of an echo lucent half‐moon sign or by systolic compression (≥10% systolic compression during the cardiac cycle).−1 min−1 every 3 minutes until the maximal heart rate on previous EE was achieved, a maximal dose of 50 μg kg−1 min−1 with up to 1.0 mg atropine was administered, or the patient developed ischemic symptoms.Hemodynamic measurements were made with the ComboWire XT Pressure and Flow Wire (Volcano). Pressure and flow velocity waveforms were taken before and at peak dobutamine stress. Pressure and flow velocities were measured at least 1 cm proximal to the MB, within the MB, and at least 1 cm distal to the MB. Dobutamine was given intravenously in increments of 10 μg kgQuantitative coronary angiography (QCA) was performed using the computer‐assisted method QAngio XA7.3 (Medis). The measurements of interest include the diameters of the reference and tunneled vessels during diastole and systole after administration of IC NTG in left anterior oblique (LAO) and right anterior oblique (RAO) cranial views. The boundaries of the tunneled vessel by QCA were confirmed by comparisons with the IVUS data.IVUS images were stored onto DVD for offline analysis. Maximum percent systolic compression was calculated by echoPlaque software  and was defined as the change in vessel area during the cardiac cycle divided by vessel area during diastole, using a single IVUS frame during manual pullback. An ECG was recorded simultaneously. The maximal plaque burden (MPB) was measured as the difference between vessel and lumen areas divided by vessel area with the largest plaque burden. IVUS length was measured from the first proximal appearance of the half‐moon sign to its distal end, or for those without the sign, the length of the compressed region.Combowire recordings were stored on the ComboMap console for offline analysis. Using a digital electronic caliper, instantaneous Pd/Pa (the fraction of diastolic coronary artery pressure divided by diastolic aortic pressure) at rest and with stress were measured throughout diastole 3 to 5 times per beat and averaged using 2 to 3 beats, to arrive at an average Pd/Pa (at rest) and average dFFR (with stress). The peak Doppler velocity was recorded for each site at rest and with stress by averaging the peak velocities over 3 beats.t‐test. Confidence intervals (CIs) were derived from the t‐test analysis. As normality of the data is difficult to ensure with small sample sizes, a nonparametric analysis was also performed with the Wilcoxon signed‐rank test. A P‐value of <0.05 was considered significant.For all continuous variables, mean and standard deviations were calculated. Hemodynamic measurements within the MB were compared to proximal and distal measurements, at rest and with stress using the paired Student Eighteen patients  with angina and EE evidence of septal wall motion abnormality at end‐systole to early‐diastole with apical sparing  were conNo patient had visually significant CAD on CA. An MB in the LAD could be seen at rest in only 5 individuals with an additional 4 apparent after administration of IC NTG. By QCA, the mean percent diameter stenosis was 21.3±2.6% during diastole and 40.4±4.1% during systole .13 In the 3 patients without the half‐moon sign on IVUS, each had a systolic compression of the LAD at rest of 20%, 23%, and 25% by IVUS. Maximal compression occurred in end systole, with delayed opening in early‐diastole, making the finding unlikely to be an artifact in vessel lumen area related to the IVUS catheter pull back. For all 18 patients, mean maximum arterial compression was 28.2±2.5%, and mean MB length was 23.7±2.8 mm. Three patients had 2 MBs. Notably, all patients had at least one visible septal branch within the region of the MB. Two patients had MBs that extended beyond the distal extent to which the IVUS could be safely advanced.IVUS revealed the pathognomonic half‐moon sign for MBs  in 15 ofAll 18 patients had coronary plaque  seen on IVUS in the proximal LAD, preceding the entrance to the tunneled vessel. The MPB was found at a mean distance of 29.8±3.2 mm proximal to the entrance of the tunnel, with 13 of 15 patients also having plaques of at least 15% within 20 mm preceding the tunnel. The lesions were not visualized on CA. The 3 patients without the half‐moon sign had a MPB of 16% to 34% proximal to the area of maximal compression of the LAD, including the 2 youngest patients .Of 15 patients with the half‐moon sign on IVUS, one was excluded because of equipment malfunction. For 2 patients, only proximal and intrabridge measurements could be obtained due to the LAD anatomy—distal measurements could not be made in one of the patients because the LAD tapered to a small‐caliber vessel preventing accurate readings, and in the other the MB extended to the apex . ThirteeRepresentative pressure and Doppler flow velocity curves  show, atQuantitative analysis showed that the baseline Pd/Pa ratio proximal to, within, and distal to the MB were near 1.0 . With peP=5 × 10−5) and distally . The velocity contour within the MB had a “fingertip” shape in all patients, characteristic for MBs.7 With stress, there was an increase in Doppler flow velocity at all positions. Average peak diastolic flow velocities proximal to, within, and distal to the MB were 64.9±5.4, 145.9±8.3, and 84.8±9.5 cm/s, respectively. Again, with stress, the peak velocity within the MB was significantly increased compared to readings made proximally  and distally . More importantly, the degree of the increase of peak velocity in the MB compared to the average of proximal and distal values was greater at stress than at rest . All these comparisons remained significant by nonparametric analysis . In viewing the dFFRs and peak velocities of all 14 subjects upon stress, an inverse relationship between the 2 parameters can be seen at each of the 3 positions sampled. Consistent with this finding, the 3 lowest distal dFFRs corresponded to the 3 highest distal peak velocities (At rest, the average peak velocity measurements proximal to, within, and distal to the MB were 26.8±2.2, 41.1±3.1, and 26.5±1.8 cm/s, respectively . The pealocities B.In our study of symptomatic patients with a distinctive focal wall motion abnormality upon EE, we invasively confirmed the presence of an MB by IVUS, by identification of an echo lucent half‐moon sign and/or systolic compression, and also demonstrated significant hemodynamic disturbances associated with the MB, including a marked increase in flow velocity and an abnormal dFFR during dobutamine stress. Also, all patients had at least one septal branch within the MB segment in concordance with a focal abnormality seen on EE. This is the first time, to our knowledge, that a noninvasive functional abnormality for the identification of an MB has been identified and undergone extensive invasive correlation in patients with anginal symptoms.11 found that dFFR under dobutamine stress measured distal to the bridge was abnormal only in a minority of patients with angiographically confirmed MBs, leaving the question of why an abnormal value of this hemodynamic measurement of ischemia was not found more consistently in this cohort of symptomatic patients. Our observation of a focal, end‐systolic/early‐diastolic buckling of the septum with apical sparing on EE, in a similar patient population, led to the hypothesis that the hemodynamic disturbance and, thereby, ischemia was local to the MB rather than distal to it.In previous work, Escaned et al14 measured diastolic blood pressure proximal to, within, and distal to the MB in 12 patients in the resting state and found a trend toward lower diastolic pressure intrabridge with pressure recovery distally. This hemodynamic change in the Pd/Pa ratio should be exacerbated under dobutamine stress within the bridge.There is literature supportive of this concept. Klues et alThe most common finding in the patients in our cohort was an abnormal dFFR that was present only within the bridge. We posit a model of ischemia involving the Venturi effect . During 11 thereby possibly obscuring the true velocity and pressure measurements distal to the long and serial bridges. We hypothesize that we were simply not able to extend the distal pressure measurement far enough to be truly outside of the MB during stress in these 3 cases.For the 3 subjects in our study who had an abnormal distal dFFR, 2 had the longest and second longest MBs, and the other harbored 2 serial MBs. It is possible that the length of arterial compression increased with dobutamine stress, a phenomenon reported previously by Escaned et al,6 The smallest luminal area of the MB is in late‐systole and very early‐diastole, hence this is when flow is most restricted. The timing of this area change differs from a fixed stenosis, in which the area does not change between systole and diastole. Also, in normal coronary physiology, the proportion of coronary flow during systole increases with an elevated heart rate, to compensate for the decrease in diastolic filling time.15 With a lumen area reduction at end‐systole and early‐diastole in MBs, this adaptive mechanism for maintenance of adequate blood flow with exercise may be compromised.Another corroborative observation of the timing of the end‐systolic to early‐diastolic wall motion abnormality is found in the cross sectional area tracings at the site of compression by IVUS, noted in this study as well as in another report.16 We believe that the septal buckling we have described on EE corresponds temporally to the late systolic dip in the radial strain described by Jhi et al although their invasive confirmation of MB was by CA alone. The mechanism behind this biphasic wall motion and radial strain are not known and will require further investigation. We speculate that maximum systolic compression of the MB in late systole, followed by relaxation in diastole, is related to these phenomena.Jhi et al recently reported a finding on speckle‐tracking strain echocardiography of a “bi‐phasic” or “double‐peak” radial strain with dobutamine stress associated with MBs.The major limitation was the lack of a control group in this proof‐of‐concept study. We could not justify these extensive invasive measurements in patients with normal EE. Thus, sensitivity, specificity, and other standard measures for validating a putative test were not estimated. These parameters will need to be established before our echocardiographic findings can be widely adopted for routine clinical care. Additionally, the sample size of this cohort was relatively small and 3 patients without the IVUS half‐moon echo‐lucent sign were not studied with dobutamine as the procedural delay to allow offline analysis for MB confirmation could not be justified for this study. Furthermore, it may not be possible to reach the distal LAD in long MBs with small distal segments. Also, with stress the optimal definition of the Doppler signal can be challenging to record when the patient is in pain and is tachycardic. Finally, we do recognize that because the constriction may not be uniform within all bridges and can change with time, there could be dynamic changes in velocity and pressure, requiring more complex modeling for further mechanistic validation.We have identified a novel EE finding, consisting of a transient focal buckling in the end‐systolic to early‐diastolic motion of the septum with apical sparing which correlates prospectively with the presence of LAD MB by IVUS, in a cohort of symptomatic patients. All patients with invasive hemodynamic measurements under dobutamine stress demonstrated an abnormal dFFR within and/or distal to the MB, consistent with MB‐related ischemia. Finally, we found that our pressure and Doppler flow results support the concept that the Venturi effect may underlie the focal abnormalities seen during noninvasive and invasive functional testing.The potential to detect physiologically important myocardial bridging noninvasively using exercise echocardiography is promising, and we hope this report will encourage other physicians and investigators to consider further evaluation of patients with angina and suspected MBs.


Until now, only some selective features of this extremely complex physiological state were highlighted in the definitions–oxygen consumption, cardiac preload and afterload, left ventricular remodeling and dysfunction, ventricular filling pressures, neurohormonal responses, exercise capacity, etc. The new American and European guidelines and recommendations include new information and have the declared intention to simplify and clarify the previous recommendations.Heart failure is a clinical syndrome in which patients have featured symptoms typical of heart failure  and typical signs of heart failure  and objective evidence of a structural or functional abnormality of the heart at rest . A clinical response to a pharmacological therapy directed to heart failure is not sufficient for the diagnosis of heart failure, although the usefulness/efficacy of the treatment may be established by the improvement in symptoms or signs (e.g. diuretic administration). Heart failure may be classified by structural abnormality (ACC/AHA), or by symptoms relating to functional capacity (NYHA).ACC/AHA stages of heart failure (based on structure and damage to heart muscle)Stage A: At high risk for developing heart failure. No identified structural or functional abnormality; no signs or symptoms.Stage B: Developed structural heart disease that is strongly associated with the development of heart failure, but without signs or symptoms.Stage C: Symptomatic heart failure associated with underlying structural heart disease.Stage D: Advanced structural heart disease and marked symptoms of heart failure at rest despite maximal medical therapy.NYHA functional classification   is a clinical syndrome caused by the action of a factor with brutal effect, often reversible, over the functional capacity of the heart.Acute heart failure is defined by the rapid onset of signs and symptoms (secondary to cardiac dysfunction) resulting from impaired heart. It may occur in the presence or absence of preexisting heart disease. Acute heart failure may be an expression of systolic or diastolic dysfunction, heart rhythm abnormalities, or disturbances of preload or afterload. It is often a threat, life threatening, requiring emergency treatment.Acute heart failure may present as acute de novo heart failure (a patient without known preexisting heart disease) or acute decompensation of chronic heart failure. In practice, the most common form is decompensation of chronic heart failure.Classification of heart failureNew onset: First presentation, Acute or slow onsetTransient: Recurrent or episodicChronic: Persistent and Stable, worsening, or decompensatedOther forms of acute heart failure (ICA) include: acute heart failure with hypertension, pulmonary edema, cardiogenic shock, heart failure with increased cardiac output and right heart failure.There is a number of well-known classifications that are used in the context of acute heart failure secondary to a myocardial infarction: Killip classification  and ForrKillip classification : DesigneStage Ⅰ: No heart failure. No clinical signs of cardiac decompensation Stage Ⅱ: Heart failure. Diagnostic criteria include rales, S3 gallop, and pulmonary venous hypertension. Pulmonary congestion with wet rales in the lower half of the lung fields. Stage Ⅲ: Severe heart failure. Frank pulmonary oedema with rales throughout the lung fieldsStage Ⅳ: Cardiogenic shock. Signs include hypotension (SBP b90 mmHg), and evidence of peripheral vasoconstriction such as oliguria, cyanosis and sweatingForrester classification; DesigneNormal perfusion and pulmonary wedge pressurePoor perfusion and low PCWP (hypovolaemic)Nearly normal perfusion and high PCWP (pulmonary oedema)Poor perfusion and high PCWP (cardiogenic shock)Another classification of severity of acute heart failure, used in some intensive care and coronary units, has been validated for cardiomyopathy,based onPatients are divided into 4 classes based on two clinical criteria: assessment of perfusion/peripheral circulation and skin appearance and pulmonary congestion (appreciated by auscultation). Class Ⅰ warm skin without ralesClass Ⅱ warm skin, rales presentClass Ⅲ cold skin, without ralesClass Ⅳ cold skin, rales presentThis classification allows an accurate assessment of prognosis regarding the patients with cardiomyopathy.Heart failure is a clinical and functional diagnosis, expression of supply / demand balance alteration; a relation in which both terms are equally important. A simple, objective, definition of chronic heart failure is difficult as long as there are no precise boundaries between ventricular and heart dysfunction .The cardiologist's interest all over the world has been directed, for a long time, to the study of the systolic function of heart, being considered the key in the pathophysiology of heart failure. In the last decade, numerous studies have attempted to shed light on natural history, pathophysiology, diagnosis, prognosis and treatment of heart failure with diastolic dysfunction.Epidemiological and clinical studies applied on hospital populations revealed that a percentage of 30–50% of patients with heart failure have preserved left ventricular function. Epidemiological data in patients with diastolic dysfunction are still very limited compared to available data on epidemiology of heart failure with systolic dysfunction, much more studied and well–documented.Diastolic heart failure is characterized by 3 basic elements: the presence of signs and symptoms of heart failure, preserved left ventricular systolic function (ejection fraction >45%) and the presence of abnormal diastolic function  .We must make a clear delimitation between two different concepts: diastolic dysfunction and diastolic heart failure. Diastolic dysfunction characterized by abnormal mechanical properties and diastolic heart failure, is a clinical syndrome characterized by signs and symptoms of heart failure and evidence of altered diastolic function.The concept of diastolic dysfunction defined by the existence of an abnormality of one or both of the constituent processes of diastole: relaxation and compliance. They may suffer elongation, delays or they may be incomplete, changes that can be measured with Doppler echography or cardiac catheterization. These aPopulation studies estimate that approximately 5% of the general population have isolated diastolic dysfunction; systolic dysfunction has a similar rate, about half being asymptomatic.The main etiology of heart failure in developed societies is ischemic heart disease. In this context, many signs of heart failure are associated with left ventricular systolic dysfunction, although diastolic impairment at rest is usually present.Diastolic dysfunction in young patients is rare (about 15% in populations under 50 years), but it increases in importance in the elders (50% in patients over 70 years) –22.Diastolic dysfunction is more common in women in whose systolic hypertension and myocardial hypertrophy contribute to cardiac dysfunction, 24.Although most patients with acute pulmonary edema have a systolic dysfunction, many cases of developing a clinical picture of acute pulmonary edema in patients with diastolic heart failure with preserved systolic function are described in literature.Among the patients with chronic heart failure, a significant percentage has diastolic heart failure with preserved systolic function, if we take into account left ventricular ejection fraction at rest, 26.Diastolic and systolic heart failure cannot be considered as separate pathophysiological entities, they coexist in most patients with the dominance of one or the other. Most paA number of other descriptive terms was frequently used in the past, but now they are used only occasionally, their clinical value being reduced. These terms do not provide information on the etiology and they have a reduced influence in establishing a modern heart failure therapy.The terms of right and left heart failure, forward and backward HF, high and low output HF, mild, moderate, or severe HF are old terms used somehow arbitrary, expressing an imprecise measure of this complex clinical syndrome.Currently, the assessment of dyspnea and the limitation of the daily work are done by classifying the patient in functional class NYHA–New York Heart Association and the decline of functional assessment is performed using the Katz ADL Scale-Activities of Daily Living.Heart failure is a clinical syndrome, which, epidemiologically, is in a continuous growth in the economic developed countries and the developing ones, in contrast to ischemic heart disease, which is declining in the developed countries, due to the prevention programs. This fact is due to an aging population and to significant advances in the diagnosis and pharmacological treatment of heart disease.Congestive heart failure (CHF) is a major public healthcare problem, being an invalidating condition, with a bad long–term prognosis, which reduces the quality of life and has a considerable economic cost to the individual and the society in general.Current estimates show that CHF affects over 5 million people in the U.S., approximately 2% of adults and 10% of elderly people beeing affected by this ‘cardiovascular epidemic’ which was designated as national research priority.With an incidence of over 400,000 new cases diagnosed each year, and appToday it is estimated that the prevalence in the European countries ranges between 0.4 and 2%, the stuThe prevalence of heart failure increases with age, the aveThe large number of studies carried out on large lots of heart failure patients shows the attention given to heart failure in clinical practice. We must note that most studies that refer to therapeutic management addresses to patients with heart failure and systolic disfunction, fewer to patients with preserved systolic function and heart failure.In the last decade special attention has been paid to diastolic heart failure,  pathopDiastolic heart failure receives increasing interest from clinicians around the world because its clinical and epidemiological significance proved to be growing. In the As mentioned above the prevalence of heart failure increases with age, the aveLooking at the percentage of patients with diastolic heart failure from the  people with symptomatic CHF we can notice a clear increase with age. Diastolic HF percentage varies from a rate of approximately 15% in populations under 50 years, to 33% in the 50–70 years age group and 50% in patients over 70 years, 40, 41.Recent clinical studies in patients with CHF and population observations estimate that heart failure with preserved systolic function represents  approximately 30–50% of cases hospitalized for symptomatic heart failure and more than 50% for people over 65 years, 42–44.Increasing prevalence of diastolic dysfunction in the elderly people is due to: age related to physiological changes  and induced pathophysiological changes associated comorbidities – essential hypertension (most important factor), ischemic heart disease, diabetes and left ventricular hypertrophy. With age there is a higher prevalence of these factors which may explain an increased percentage of patients with distolic dysfunction in the elderly people. The risIn younger age groups, patients under 50 years, heart failure as a whole (patients with systolic dysfunction and diastolic dysfunction) is more common in men. At this age the most common etiology is ischemic coronary disease, more common in males. The main causes of heart failure are: coronary heart disease (70% of patients with HF), valve disease and cardiomyopathies each with approximately 10% of cases. In elderly people prevalence is equal between the sexes[Numerous epidemiological reports have noticed that women with heart failure have an increased percentage (than men) of preserved systolic function, 46, 47.In similar age groups and associated clinical conditions female patients have more diastolic heart failure than men. Out of the 2.4 million female patients with heart failure in the U.S. more than 50% of them have normal systolic function .There is no registry of heart failure in Romania as there is in other countries, so there is no precise data on the epidemiology of heart failure. Older data estimate a heart failure prevalence of 0.2–0.5% in the general population, that means approximately 150,000–200,000 patients with heart failure diagnosis. Recent HF morbidity is particularly important, patients with heart failure require frequent medical visits at home or rehospitalization, which represent a significant expenditure of health resources. In the first year after hospital discharge approximately 50% of patients with heart failure require rehospitalization, the data are similar in those with systolic dysfunction or diastolic dysfunction.Heart failure is the main cause of hospitalization in the Medicare population in the USA. Data frEpidemiological data show that morbidity is decisively influenced by age,  rehospitalization rate (at one year) increases from 25% for under 50 years age group, to 50% for 50–70 years age group . Some European studies show that about 1% of the national health budget is allocated to the therapy of heart failure, in the U.S. about 2% of the national health budget is allocated to this problem. The large number and the long length of hospitalization for acute heart failure or decompensation of chronic heart failure are a substantial economic burden for the healthcare budgets. In U.S., the first cause of hospitalization in patients over 65 years is heart failure. In Scotland, the number of patients with heart failure in hospital increased by 60% between 1980 and 1990. The United States spends about  20 billion dollars annually, 10% of healthcare budget allocated for the management of cardiovascular disease with heart failure, 75% of the amount being allocated to hospital care. Heart failure is the most expensive cardiological syndrome ,57.Prognosis is heterogeneous and depends on the heart failure class, its etiology and the patient's age. The prognosis of untreated heart failure is unknown. Multiple studies and metaanalyses highlighted various predictive criteria: clinical–radiological , presence of atrial fibrillation, ejection fraction of VS, maximal O2 consumption during exercise, 6–minute walk test, pulmonary capillary pressure, serum catecholamine, natriuretic peptides and ventricular arrhythmias.The latest ESC guidelines summarize the knowledge about the conditions associated with a poor prognosis in heart failure:Framingham's study reported a 65% survival rate at 1 year after specifying the diagnosis of heart failure, respectively 25% in men, and, 35–40% in women, meaning 5 years survival.  Another study–Mayo Clinic–Minnesota, shows a similar 66% one–year survival after the diagnosis indication. The main causes of death are sudden death or terminal heart failure (50% of the cases). Depending on the functional NYHA class in which the patients are reported, different mortality rates are recorded: CONSENSUS Ⅰ studies elderly patients with heart failure; NYHA class ⅓, reports a mortality rate of 44% at 6 months, and the ⅤHeft and SOLVD study shows a mortality rate of 15–20% at 1 year, in patients in NYHA class Ⅱ and Ⅲ. Patients with acute heart failure have a very severe prognosis, large randomized trials with hospitalized patients for decompensated heart failure have shown a 9.6% mortality rate at 60 days and a 35.2% combined mortality rate and rehospitalization at 60 days, 59. Ischemic etiology proves to be a negative prognostic factor in AIRE and TRACE studies on patients with post–myocardial infarction heart failure, a 14–25% mortality rate in the 1 year registered in these patients. Mortality is particularly high in patients with acute myocardial infarction associated with severe HF, with a mortality rate close to 30% in the 1 year, 60.Important observational studies that include patients with both systolic and diastolic heart failure show that although short–term mortality rate may be lower in patients with diastolic dysfunction, long–term survival analysis shows a similar mortality rate for both groups of patients, especially those over 65 years, 46. DifAnother determinant of mortality is the age, mortality in diastolic heart failure increases significantly with age. The data show that mortality at 5 years is 15% in below the 50–year–old group, 33% in 50–70 year–old group, reaching 50% in patients over 70 years old. Thus, in the elderly people over 70 years old the mortality rate for heart failure diastolic and heart failure systolic is practically equivalent, 46.Patterns of morbidity and mortality in Romania have undergone significant changes in the recent decades, due to the increased incidence and prevalence of chronic disease and mortality associated with these causes, in the context of the increasing percentage of elderly population, coupled with the action of multiple biological, environmental, behavioral risk factors as well as the influence of the socio–economic conditions and healthcare.Compared to the average of the first 15 states included in the European Union (EU–15) and the average of the new member states (NMS–10), the overall mortality, has shown a slow downward trend . RomaniaThere are not sufficient epidemiological data yet  on diastolic heart failure in Romania, some studies show a high mortality rate, at 1 year up to 29% in the diastolic heart failure lot and 33% in systolic .Prognosis of individual patients differs considerably, outcomes in highly variable trial data often do not give an adequate direction; taking into consideration the magnitude of this syndrome in the society and its complexity, we need a model to predict the risk of death, to estimate survival of heart failure patients. Survival analysis is a branch of statistics dealing with the life eextent of biological organisms. More generally, the survival analysis involves estimating the duration of survival until a certain event. In this context, in the specialized literature devoted to survival analysis, death is considered an ‘event’. Survival analysis seeks to answer the questions related to the survival of an individual or a lot from a population, over a certain period of time, and which are the causes of increase or decrease in the extent of survival.survival function, usually noted by S and defined as: S(t)=Pr(T>t) in which–t represents one moment in time;	T is a random variable designating the time (or age) of death;Pr notes the probability of occurrence of an event. Pr(T>t) means the probability that the time of death T occurs some time after the specified time, t.A key element in this area is the 2)< S(t1) for the moments of time t2>t1. Last property shows that the survival function is monotonously decreasing in time. Survival at a later age is only possible if the subject has survived to all younger ages. Also, for the usual mathematical functions used for survival models, the value of S (t) function tends to 0 (zero) at a time when t tends to infinity.Usually, survival function S(t) has the following two properties: S(0)=1; S(tlifetime distribution function (life extension) by the relation: F(t)=Pr(T<t)=1–S(t). Pr(T<t) means the probability that death time T occurs before or at a specified time t, at the latest.In connection with the survival function we can define the hazard function, conventionally denoted by h (t). Hazard function can be defined in mathematical terms as in the relation Another extremely important concept is the in which S'(t) represents time derivative of survival function. Hazard function is the mortality rate at time t conditioned by survival until time t or later (T>t). Hazard function is non negative, this meaning that h(t)>0.Survival models commonly use hazard function or hazard function logarithm. For example, a parametric model of the hazard function logarithm, based on a multiple linear distribution can be written as i1, xi2, …, xin and the a1, a2,…, an, are the coefficients of the model. In this relation alpha is a kind of reference function/value (baseline function), because loghi(t)=alpha when all independent variables are zero. The purpose of multiple regression is to highlight the relationship between a dependent variable and many independent variables .In these equations the index i represents the number of observation, the index n is the number of independent variables noted xOne of the most used functions of survival is the Cox multiple regression model , proportIn this case we have:which will result in a hazard function0(t)is called baseline hazard function. In Cox's model it is unspecified.hTaking two observations, i and j in equationSince hazard functions as hazard ratio for any pair of observations, according to Cox's model can be actually extended to include time–dependent variable x. In this case, however, Cox's model is no longer a proportional hazards model. In this paper as in the vast majority of used applications, Cox's model is used for variable x independent of time. The equation 1, a2,…, an, x is n–dimensional column's vector of independent variables with components x1,x2, …, xn, and T designates the sign of transposition of a vector.in which a is n–dimensional column's vector of model parameters, with components aSurvival function for Cox's proportional hazards model Figure 100(t) respectively for H0(t) we can determine the values on experimental bases or we may use known statistical models: exponential, Weibull or Gompertz[For baseline hazard function h Gompertz.To determine the major factors that allow the forecasting survival  we may use Cox's multiple regression model, the proportional hazards model.The next step is to fit the requested regression model to all data and to create a heart failure prognostic model. The number of individuals living with heart failure is steadily increasing and there are many applications of such a model that may estimate the survival of a patient with heart failure.


An early and accurate diagnosis of chronic heart failure is a big challenge for a general practitioner. Assessment of left ventricular function is essential for the diagnosis of heart failure and the prognosis. A gold standard for identifying left ventricular function is echocardiography. Echocardiography requires input from specialized care and has a limited access in Swedish primary health care. Impedance cardiography (ICG) is a noninvasive and low-cost method of examination. The survey technique is simple and ICG measurement can be performed by a general practitioner. ICG has been suggested for assessment of left ventricular function in patients with heart failure. We aimed to study the association between hemodynamic parameters measured by ICG and the value of ejection fraction as a determinant of reduced left ventricular systolic function in echocardiography.A non-interventional, observational study conducted in the outpatients heart failure unit. Thirty-six patients with the diagnosis of chronic heart failure were simultaneously examined by echocardiography and ICG. Distribution of categorical variables was presented as numbers. Distribution of continuous variables was presented as a mean and 95% Confidence Interval. Kruskal-Wallis test was used to compare variables and show differences between the groups. A p-value of <0.05 was considered significant.We found that three ICG parameters: pre-ejection fraction, left ventricular ejection time and systolic time ratio were significantly associated with ejection fraction measured by echocardiography.The association which we found between EF and ICG parameters was not reported in previous studies. We found no association between EF and ICG parameters which were suggested previously as the determinants of reduced left ventricular systolic function.The knowledge concerning explanation of hemodynamic parameters measured by ICG that is available nowadays is not sufficient to adopt the method in practice and use it to describe left ventricular systolic dysfunction. Chronic heart failure (HF) is a complex syndrome characterized by a long period of sub-clinical symptoms and progressive process associated with poor prognosis. The five-year mortality is six times higher than in general population. The pre10-20% at 70–80 years of age. The incThe majority of patients at risk of chronic HF, e.g. with coronary heart disease and hypertension, are treated in primary health care.An early and accurate diagnosis of HF is a big challenge for a general practitioner. Assessment of left ventricular function is essential for the diagnosis of HF and the prognosis. The 5-year survival rate correlates with reduced left ventricular systolic function and decreases in patients with HF to 53% compared with 93% in age- and sex- matched general population. A gold We aimed to study the association between ICG parameters and the value of EF in echocardiography. If the association was found, ICG could be a method to evaluate reduced left ventricular function.This was a non-interventional, observational study. The study was conducted in the outpatients heart failure unit at the Blekinge County Hospital in Karlshamn in Sweden during the period 6 February 2009 – 6 March 2009. Informed consent was obtained from each participant. There were 63 patients with the diagnosis of chronic HF registered at the heart failure unit. All registered patients were offered participation by a letter send by a cardiologist. No reminder was send. Heart failure unit is the secondary care unit. Patients are referred there from primary care if difficulties with management of chronic HF occur. Diagnosis of chronic HF was established before referral. We thought that it was not necessary to question the diagnosis and we did not penetrate the way it was made.Exclusion criteria comprised significant aortic valve insufficiency and severe aortic stenosis, both of which influence ICG measurement.The patients were examined by means of echocardiography and ICG during one consultation.Both echocardiography and ICG were performed once in each patient. Echocardiography was performed by an experienced cardiologist using Vivid 7, GE equipment. EF was calculated according to modified Simpson’s formula. The following echocardiographic criteria were used to describe left ventricle systolic function: EF ≥ 50% normal systolic function,EF 40–49% mildly impaired systolic function, EF 30-39% moderately impaired systolic function, EF <30% severely impaired systolic function. ICG was performed by a general practitioner with experience of survey technique using Niccomo™ monitor .Two pairs of dual sensors were placed on the patient’s neck and two on the sides of the chest Figure . The skiICG measurement was obtained after 10 minutes resting, in the supine position with the head elevated between 30–45 degrees for better comfort of the patient. Data were transferred to an external disc and analysed thereafter regarding their adequacy.None of ICG parameters can be directly compared with EF due to differences in both methods of examinations. ICG parameters were divided into the following groups:1. Expression for cardiac work: cardiac output, stroke volume, left cardiac work.2. Contractility: velocity index, acceleration index, Heather index.3. Fluid status: thoracic fluid content.4. Expression for systolic function: pre-ejection period, left ventricular ejection time, systolic time ratio and ejection time ratio.5. Expression for the vascular resistance the heart works against: systolic vascular resistance.We decided to analyse cardiac output, stroke volume, left cardiac work and systolic vascular resistance related to the body surface as cardiac index, stroke index, left cardiac work index and systolic vascular resistance index.The study was approved by the research ethics committee at Lund University.Data were analysed in the STATA version 10 . Distribution of categorical variables was presented as numbers. Distribution of continuous variables was presented as a mean and 95% Confidence Interval. Kruskal-Wallis test was used to compare variables and show differences between the groups. A p-value of <0.05 was considered significant.We obtained consent for participation from 37 patients out of 63 patients registered at heart failure unit. Those 37 patients were enrolled into the study. ICG could not be performed in one patient due to distortions in the ICG signal and this patient was excluded from further calculations. The mean age of 36 patients was 68.3 years (CI 64.2-72.4).The group comprised 28 men (78%) and 8 women (22%). The mean age for men was 68.2 (95% CI 64.0 -72.4) and for women 68.5 (95% CI 54.7-82.3). None of the patients had significant aortic valve insufficiency or severe aortic stenosis. None of the patients reported any discomfort or adverse reaction associated with ICG measurement.Normal left ventricular systolic function was presented in 13 out of 36 patients (36%), mildly impaired in 9 patients (25%), moderately and severely impaired each in 7 patients, respectively (19%). Three ICG parameters: pre-ejection fraction, left ventricular ejection time and systolic time ratio were associated with EF with significant p-value.The results are presented in Table The purpose of this study was to find whether there is any association between EF measured by echocardiography and hemodynamic parameters measured by ICG.We found associations between EF and three of four ICG parameters which describe systolic function of the left ventricle: pre-ejection period, left ventricular ejection time and systolic time ratio. We did not find any association between EF and the fourth parameter which describes systolic function - ejection time ratio, though it is directly proportional to left ventricular ejection time. We cannot explain this. The technique of ICG examination was correct. Only one examination had insufficient quality, most likely due to a bad contact between a sensor and the skin. There was no other potential cause of the distortions in ICG signals. We do not think that the patients’ condition could influence the quality of ICG examination and therefore our results. All grades of HF were represented in our study population. None of the patients had unstable HF - a condition which can influence the quality of ICG examination.A limitation of our study is a small number of patients. Nevertheless, most of the previous studies concerning the correlation between ICG and echocardiography had a small number of participants. This might be a reason why the results are not ambiguous. Evaluation of left ventricular function was the subject in previous studies with ICG but none of the parameters we found associated with EF was previously regarded as a determinant of left ventricular systolic dysfunction. Systolic time ratio, however, was able to distinguish preserved from impaired EF. Also, aThe following ICG parameters were suggested in another study as determinants of left ventricular systolic dysfunction: cardiac index, left cardiac work index and systolic vascular resistance index. We coulThe lack of association between cardiac index and EF found in our study confirms a lack of agreement between absolute values of cardiac output measured by ICG and by echocardiography. We did According to the theoretical equation EF is a quotient of stroke volume and end diastolic volume, cardiac output is a product of stroke volume and heart rate. ICG was considered to be a reliable method to determine stroke volume. Owing tNo association between stroke volume index or cardiac output index and EF was found in our study.EF is commonly used to describe cardiac contractility. We expeThe possibility to determine left ventricular function by ICG makes the method attractive for use in patients with HF in primary health care. The association which we found between EF and ICG parameters was not reported in previous studies.We found no association between EF and ICG parameters which were suggested previously as the determinants of reduced left ventricular systolic function. We do not think that knowledge concerning explanation of hemodynamic parameters measured by ICG that is available nowadays is sufficient to adopt the method in practice and use it to describe reduced left ventricular function.HF: Heart failure; EF: Ejection fraction; ICG: Impedance cardiographyThe authors declare that they have no competing interests.EK participated in the design of the study, carried out the data collection, helped with data interpretetion and drafted the manuscript.SS helped with the design of the study, data collection and draft of the manuscript. HO helped draft the manuscript. AH designed the study, performed the statistical analysis, handled the data set, interpreted the data, partcipated in drafting the manuscript. All the authors read and approved the final manuscript.


Although cine magnetic resonance imaging (MRI) is considered the gold standard for evaluation of left ventricular (LV) volumes, mass, and systolic function, assessment of diastolic filling is still challenging. The aim of this study was to assess the impact of LV mass on diastolic function by time-volume curve obtained from cine MRI in patients with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) and normal subjects.Cine MRI was performed in 10 healthy controls, 11 HCM patients, and 11 DCM patients. LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), LV mass, and LVESV/mass ratio were calculated by tracing endocardial and epicardial borders of LV in 8-10 short axis views. Furthermore, to assess the LV diastolic function, the peak filling rate (PFR), time to PFR (TPF), and first third filling fraction (1/3 FF) were calculated from the first derivative curve of the time-volume curve. Temporal resolution was 30 frames per R-R interval.Resting LVEF were 54±4% in Control group, 26±9% in DCM group, and 62±6% in HCM group. LVSV were similar in 3 groups. LV mass was greater in DCM and HCM group compared to Control group. TPF of HCM groups was longer than both Control and DCM groups. PFR and 1/3FF were greater in Control group compared to both DCM and HCM groups. LV mass showed significant inverse relationship with PFR  and 1/3FF .LV diastolic parameters can be assessed non-invasively by time-volume curve analysis. LV mass has influence on diastolic filling.None.


A 31-year-antenatal lady with critical mitral stenosis presented for emergency caesarean section with fetal distress. She had acute onset atrial fibrillation. She was given a combined spinal epidural (CSE) anaesthesia and her arrhythmia was successfully managed after delivery of the baby with intravenous calcium channel blocker. Mitral stenosis is the most common valvular heart disease complicating pregnancy in developing countries. The physiological changes during pregnancy may exacerbate their cardiac symptoms. They may present with complications like congestive cardiac failure, atrial fibrillation, or pulmonary thromboembolism during the antenatal, intrapartum, or postpartum period. Here we discuss the management of parturient woman with high maternal and fetal risk presenting for emergency caesarean. The merits of regional anaesthesia and the importance of invasive monitoring are also discussed. Her haemoglobin was 11.7 g%. She was advised a fresh echocardiograph and the risk of anaesthesia was explained to her. The next day she presented for emergency CS with onset of preterm labour and a nonreassuring fetal heart rate. She was immediately taken to the operating room. On examination, the patient was dyspneic at rest and unable to lie supine. She had pedal edema and her jugular venous pulse was raised. A 2D echocardiography done only that morning revealed critical mitral stenosis with mitral valve area of 0.7 cm2, severe tricuspid regurgitation, mild aortic regurgitation, and pulmonary artery hypertension. Her ejection fraction was 60%. She was propped up with 2 pillows and given O2 by face mask at 12 L/min. An intravenous access was secured with an 18G cannula, Ringer lactate was started, and a defibrillator was kept ready. ECG, NIBP, and SpO2 monitors were attached. Her pulse was irregularly irregular and the ECG showed atrial fibrillation with a ventricular rate of 142/min. Her blood pressure (BP) was 106/60 mmHg. Her respiratory rate was 32/min but her chest was clear and saturation was 100% with oxygen therapy. A 20G arterial cannula was inserted in the radial artery for invasive blood pressure monitoring. The arterial blood gas analysis showed pH 7.5, PO2 98 mmHg, PCO2 30 mmHg, HCO3 20 mmol/L, Na+ 134 mmol/L, and K+ 3.8 mmol/L. Combined spinal epidural (CSE) anesthesia was planned for the surgery. An 18G CSE was inserted in the first attempt at L3/4 intervertebral space using loss of resistance to air in the sitting position. In the subarachnoid block, 6 mg (1.2 mL) of 0.5% Bupivacaine with 25 μg fentanyl was injected through a 27G needle after CSF aspiration. The epidural catheter was inserted 5 cm into the epidural space and fixed. The patient was made to lie over 2 pillows as she could not tolerate a supine position. A wedge was also placed below her right hip to allow left uterine displacement to prevent aortocaval compression. Her BP dropped to 72/50 mmHg which increased to 92/54 mmHg with 6 mg ephedrine. The sensory level achieved was T10 and epidural top up of 3 mL of 2% Xylocaine with adrenaline was given in aliquots of 1 mL to achieve a level of T6 when the surgery commenced. She required one more dose of 6 mg Ephedrine to maintain her systolic BP above 90 mmHg. Her ventricular rate rose to 172/min during this period. The baby was delivered within 5 minutes of abdominal incision. The 2.2 kg male baby had aspirated thick meconium and required endotracheal intubation, tracheobronchial suctioning, and mechanical ventilation. After delivery of the baby, 10 units of oxytocin was added to the mother's drip. Her BP was 92/60 mmHg and keeping all preparations ready for emergency cardioversion, she was given 15 mg of Diltiazem injection in 5 mg boluses to obtain a ventricular rate of 90/min. Her ECG reverted to sinus rhythm. Her systolic BP rose to 110 mmHg and she did not require any further vasopressors. A peripherally inserted central venous catheter was inserted to measure the central venous pressure. The rest of the surgery was uneventful. She received 500 mL of RL including 10 units of oxytocin and her urine output was 50 mL. She was shifted to the ICU for postoperative observation and monitoring. In the ICU, she received oxygen therapy, diuretics, epidural analgesia, and intravenous fluids guided by central venous pressure. Invasive BP monitoring was continued for 24 hours. An infusion of amiodarone was used to maintain sinus rhythm and rate. Postoperatively, continuous hemodynamic monitoring was done with invasive monitors, intra-arterial blood pressure, and central venous pressure monitoring. She remained hemodynamically stable and had no episode of tachyarrhythmia, pulmonary edema, or thromboembolism during her stay. The next day, she was started on oral diltiazem and subcutaneous low molecular weight heparin and shifted to the ward on the postoperative day 2 from where she was discharged 7 days later. The neonate developed meconium aspiration pneumonia and died on day 3 of life.A 31-year-old lady presented to the antenatal clinic at 34 weeks of gestation with increasing shortness of breath. She was a known case of rheumatic heart disease with mitral stenosis and had undergone balloon mitral valvotomy 12 years ago and closed mitral commissurotomy 7 years ago. She was gravida 8, para 2 with 5 spontaneous abortions and had undergone caesarean section twice since the commissurotomy but had only one living issue who was 3 years old. The other had died a neonatal death. She was on oral Digoxin 0.25 mg od and penicillin prophylaxis since the past seven years. During the present pregnancy, her dyspnea had progressed from NYHA class II to class III. She was put on bed rest and started on diuretics. As part of her workup for elective caesarean section for obstetric reasons, she presented for preanaesthesia evaluation. On auscultation of the heart, she had a mid-diastolic murmur in the mitral area and loud P2. She had no signs of congestive cardiac failure. Her electrocardiogram showed a normal sinus rhythm with a heart rate of 80/min. She had a normal coagulation profile with prothrombin time 13/13, activated partial thromboplastin time 29/31, and platelet count 210 × 10Rheumatic mitral stenosis is not uncommon in developing countries and can complicate up to 88% of pregnant patients with heart disease . As in oHere, we discuss the case of a 34, week antenatal lady with critical mitral stenosis who presented for emergency Caesarean section with acute atrial fibrillation (AF). The acute onset <48 hours) of her arrhythmia was evident as her preanaesthetic evaluation done the day earlier showed her to be in sinus rhythm. As her BP was 100/60 with severe fetal distress and no symptoms of angina or acute heart failure  has been hours ofThe CSE anaesthesia has been used for CS successfully in several cardiac patients . A CSE w2) [Once the baby was delivered, the increased venous return enabled us to achieve rate control with Diltiazem. As rate control is not inferior to rhythm control  in preve2) . The cau2) , 11 were2) , 13, but2) . The fac


New-onset atrial fibrillation in patients hospitalized for an acute myocardial infarction often leads to hemodynamic deterioration and has serious adverse prognostic implications; mortality is particularly high in patients with congestive heart failure and/or a reduced left ventricular ejection fraction. The mechanism of atrial fibrillation in the context of an acute myocardial infarction has not been well characterized and an effective treatment other than optimal medical therapy and mechanical hemodynamic support are expected.A 71 year-old male with an acute myocardial infarction due to an occlusion of the left main coronary artery was treated with percutaneous coronary intervention. He had developed severe congestive heart failure with a left ventricular ejection fraction of 34%. The systemic circulation was maintained with an intraaortic balloon pump, continuous hemodiafiltration, and mechanical ventilation until atrial fibrillation occurred on day 3 which immediately led to cardiogenic shock. Because atrial fibrillation was refractory to intravenous amiodarone, beta-blockers, and a total of 15 electrical cardioversions, the patient underwent emergent radiofrequency catheter ablation on day 4. Soon after electrical cardioversion, ectopies from the right superior pulmonary vein triggered the initiation of atrial fibrillation. The right pulmonary veins were isolated during atrial fibrillation. Again, atrial fibrillation was electrically cardioverted, then, sinus rhythm was restored. Subsequently, the left pulmonary veins were isolated. The stabilization of the hemodynamics was successfully achieved with an increase in the blood pressure and urine volume. Hemodiafiltration and amiodarone were discontinued. The patient had been free from atrial fibrillation recurrence until he suddenly died due to ventricular fibrillation on day 9.To the best of our knowledge, this is the first report of pulmonary vein isolation for a rescue purpose applied in a patient with hemodymically unstable atrial fibrillation complicated with an acute myocardial infarction. This case demonstrates that ectopic activity in the pulmonary veins may be responsible for triggering atrial fibrillation in the critical setting of an acute myocardial infarction and thus pulmonary vein isolation could be an effective therapeutic option. New-onset atrial fibrillation (AF) in patients hospitalized for an acute myocardial infarction (AMI) often leads to hemodynamic deterioration and has serious adverse prognostic implications; mortality is particularly high in patients with congestive heart failure and/or a reduced left ventricular (LV) ejection fraction,2. The mA 71-year-old male with an AMI due to a total occlusion of the left main coronary artery was treated with emergent percutaneous coronary intervention. The patient had no history of AF and was in sinus rhythm on admission to the coronary care unit. He had developed severe congestive heart failure and was on mechanical ventilation under intravenous sedation with midazolam. Echocardiography revealed an LV ejection fraction of 34% and a left atrial (LA) diameter of 46 mm. The systemic circulation was maintained with an intravenous administration of inotropes, an intraaortic balloon pump (IABP), and continuous hemodiafiltration (CHDF). Soon after admission, the patient had several episodes of ventricular tachycardia that required electrical cardioversion to terminate. Intravenous administration of amiodarone was initiated, and this effectively suppressed the tachycardia. However, AF occurred on day 3, which immediately led to cardiogenic shock. Because AF was refractory to amiodarone, beta-blockers, and a total of 15 electrical cardioversions, the patient underwent radiofrequency catheter ablation on day 4  system. Transseptal access was obtained using the standard Brokenbrough needle technique with intracardiac ultrasound and fluoroscopic guidance. Three 8 F SL0 sheaths were placed in the LA. Following pulmonary vein (PV) venography, the cardiac geometry was created by a 20-pole circular mapping catheter in all PVs, the LA appendage and the body of the LA. In order to identify the triggering vein, four electrode catheters were positioned in the following thoracic veins: a decapolar catheter in the superior vena cava, an 8-mm tip ablation catheter  in the right superior PV, and two circular mapping catheters in the left superior PV and the left inferior PV, respectively. Shortly after electrical cardioversion, ectopies from the right superior PV triggered the initiation of AF Figure. SubsequTo our knowledge, this is the first report of PV isolation (PVI) for a rescue purpose applied in a patient with hemodynamically unstable AF complicated with an AMI. The present case includes two major findings. First, AF may be triggered by ectopies from the PVs in the critical setting of AMI. Second, PVI may be effective for rhythm control and may thereby improve hemodynamic status.AF, especially a new onset of AF, has been shown to be an independent predictor of mortality in patients with AMI,2. AF maDespite the increasing evidence showing the prognostic significance of AF in patients with AMI, current therapeutic strategies in this setting seem to be limited to the management of hemodynamics, including IABP, mechanical ventilation, CHDF, and so forth. In addition, sedation with opioid analgesic drugs such as sufentanil might provide some cardioprotective / antiarrhythmic effects. These are the therapies generally given to AMI patients with congestive heart failure, but are not a specific treatment for AF. The rate control strategy may be accepted as an alternative to sinus rhythm restoration. However, attempts at rate control often fail when patients are on high levels of endogenous or exogenous catecholamines or are not able to tolerate the use of drugs including beta-blockers, digoxin, and calcium antagonists, because these agents have negative inotropic effects or may increase oxygen consumption. Furthermore, sinus rhythm should be necessary to maintain systemic circulation in patients with severe pump failure as shown in the present case. Amiodarone might be a drug that can be used in this setting. HoweverPVI has been accepted by consensus as the strategy of choice for the treatment of AF by catheter ablation. PVI exeBased on this single case report, it is premature to draw conclusions that PVI could become a standard procedure to treat AF in the critical setting of an AMI. Since PVI is still a highly complex procedure, a careful assessment of benefit and risk must be considered for each patient.Ectopic activity in the PVs may be responsible for triggering AF in the critical setting of an AMI. PVI in desperate cases, as a last resort, is feasible and could be an effective therapeutic option.Written informed consent was obtained from the patient’s spouse for publication of this case report and accompanying images.AF: Atrial fibrillation; AMI: Acute myocardial infarction; CHDF: Continuous hemodiafiltration; IABP: Intraaortic balloon pump; LA: Left atrium; LV: Left ventricle; PV: Pulmonary vein; PVI: Pulmonary vein isolation.The authors declare that they have no competing interests.IM (author of correspondence) performed pulmonary vein isolation and drafted the manuscript. TS gave final approval of the version to be published. HT and HM were involved in clinical decision making and in revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/12/110/prepub


Failed Fontan circulation who underwent heart transplantation, with focus on indications, timing, strategies, risk factors and long-term outcome.Between 1986 and 2011, 179 children underwent heart transplantation for cardiomyopathy and end-stage congenital heart disease. Fifteen patients had single-ventricle physiology and underwent Fontan procedure. Five patients  had failed Fontan circulation. Interval between Fontan procedure and failing circulation was 8-14 years. Indications for heart transplantation were ventricular failure (n=4), and protein-losing enteropathy (n=1).The technical strategy during transplantation included pulmonary artery reconstruction, redirection of the venous drainage and oversizing of the donor heart. The patient with early Fontan failure is alive 20 years post-transplantation. One patient with a late Fontan failure had acute graft dysfunction, increased pulmonary vascular resistance, chronic organ congestion and perioperative hemorrhage. A biventricular assist device was implanted but the patient died 24 hours later. Two patients with mild pulmonary hypertension died 1 month and 10 months, respectively, after heart transplantation and biventricular assist device implantation to support the failing graft. The last patient with a late Fontan failure is alive and well 8 years after transplantation. Early mortality is 20% while late mortality is 40%. At a mean follow-up of 18 years, overall survival is 40%. A risk factor for mortality is increased pulmonary vascular resistance.Heart transplantation in failed Fontan circulation, though technically challenging, may be offered in this difficult group of patients who are otherwise hopeless.


Cardiac resynchronization therapy (CRT) aims to reduce dyssynchronous contraction through simultaneous pacing of the right ventricular (RV) septum and left ventricular (LV) lateral wall. Up to 40% of patients do not respond, largely attributed to lack of dysynchrony and/or transmural scar at pacing sites. In this pilot study we tested the feasibility of guiding LV and RV leads to “optimal” segmental targets using a MRI-based 3D surface rendered cardiac model.Ten consecutive patients planned for CRT were recruited. All patients underwent cardiac MRI inclusive of cine and delayed enhancement (DE) imaging using a 3T scanner. A blinded interpreter determined the time to maximal radial wall thickening (TmWT) and myocardial scar burden for each of 16 segments. All potential LV lead targets were ranked according to scar burden (lowest first) and then sub-ranked by TmWT (highest first). All potential RV lead targets were ranked according to scar burden (lowest first). These rankings were encoded onto a surface rendered cardiac model, displayed in standard fluoroscopic views Figure  and usedMean age and LVEF was 68.5 ±6.7 years and 25.6 ±10.8%, with a mean NYHA class of 2.9 ± 0.6. “Optimal” LV and RV pacing sites differed from conventional pacing sites  in 9 and 4 patients, respectively. All patients successfully underwent CRT device implantation with a mean fluoroscopy time of 23 ± 10.9 minutes. Post-device CT imaging showed LV and RV leads to be successfully delivered to the “optimal” or immediately adjacent segment in 90% and 90% of patients, respectively. The only documented complication was a small pericardial effusion not requiring drainage in a patient that was prescribed conventional lead positioning by the model.In this pilot study we demonstrate that a targeted approach to CRT lead placement using an MRI-based cardiac model is clinically feasible. A prospective clinical trial evaluating the clinical benefit of this approach is planned.J.A.W is a clinician scientist with the Heart and Stroke Foundation of Ontario, Canada. This research was supported by the Heart and Stroke Foundation grant # NA6488 (PI: J.A.W.) and by the Canada Foundation of Innovation (CFI) Leaders Opportunity Fund.


Echocardiography is the most convenient method used to evaluate right ventricular function, and several echocardiographic parameters were studied in previous studies. But the value of these parameters to assess the right ventricular function in patients with pulmonary arterial hypertension (PAH) has not been well defined.Patients with PAH were observed prospectively. Right heart catheterization, echocardiography and cardiac magnetic resonance (CMR) were performed within 1 week interval. The correlations between echocardiographic parameters and right ventricular ejection fraction (RVEF) derived from CMR as well as hemodynamics were analyzed.r = 0.440, P = 0.015; tricuspid annular systolic excursion velocity [S’], r = 0.444, P = 0.016; isovolumic acceleration [IVA], r = 0.600, P = 0.001; right ventricular fraction area change [RVFAC], r = 0.416, P = 0.022; ratio of right ventricular transverse diameter to left ventricular transverse diameter [RVETD/LVETD], r = −0.649, P<0.001; RVMPI, r = −0.027, P = 0.888). After adjusted for mean right atrial pressure, mean pulmonary arterial pressure and pulmonary vascular resistance (PVR), only IVA and RVETD/LVETD could independently predict RVEF. Four echocardiographic parameters displayed significant correlations with PVR .Thirty patients were enrolled including 24 with idiopathic PAH, 5 with PAH associated with connective tissue diseases and 1 with hereditary PAH. All echocardiographic parameters except right ventricular myocardial performance index (RVMPI) correlated significantly with RVEF (tricuspid annual plane systolic excursion [TAPSE], The echocardiographic parameters IVA and RVETD/LVETD can reflect RVEF independently regardless of hemodynamics in patients with PAH. In addition, TAPSE, S’, RVFAC and RVETD/LVETD can also reflect PVR in PAH patients. Pulmonary arterial hypertension (PAH), caused by vascular remodeling of the small pulmonary arteries, is characterized by mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary capillary wedge pressure (PCWP) ≤15 mmHg at rest assessed by right heart catheterization (RHC). Pulmonary vascular remodeling and the RV dysfunction both play important roles in the pathophysiological process of PAH. Comprehensive evaluation of the condition of pulmonary hypertension (PH) patients requires the consideration of both the pulmonary circulation and RV function. RVEF that can reflect intrinsic RV contractility has been demonstrated to be an independent predictor of survival. Echocardiography is the most common and convenient method used to evaluate RV function and hemodynamics of pulmonary circulation, and several echocardiographic parameters have been studied in previous studies, including RV fractional area changes (RVFAC), RV myocardial performance index (RVMPI), Thus, in the present study, we attempted to analyze the correlations between the echocardiographic parameters and RVEF as well as hemodynamics, in order to systematically elucidate the role of these parameters in assessing the severity of PAH.PAH patients who were referred to Fuwai hospital between October 2010 and April 2012 for treatment were evaluated for this study. Inclusion criteria were mPAP≥25 mmHg and PCWP≤15 mmHg by RHC at rest. We excluded (1) patients with congenital heart diseases; (2) patients with unstable conditions; (3) patients with contraindication of CMR; (4) patients who refused to participate. Finally, thirty patients were recruited, and all of them underwent RHC, echocardiography and CMR within 1 week. The written informed consent was acquired from all patients enrolled. This study complied with the Declaration of Helsinki and was approved by the Institutional Review Board of Fuwai Hospital.Exercise capacity was evaluated by the WHO functional class (WHO-FC) and 6-minute walk distance (6MWD) according to the guidelines of the American Thoracic Society. Echocardiography was performed by the Philips iE33 system, and images were analyzed offline after the procedure. TAPSE was acquired by M-mode image, and the cursor was placed through the lateral tricuspid annulus, the displacement of which from the end-diastole to the end-systole was measured. The S’ known as tricuspid annular systolic excursion velocity was measured by Tissue Doppler image (TDI) in the apical 4-chamber view. The RV isovolumic acceleration was calculated as the peak isovolumic myocardial velocity divided by the time to peak velocity measured by TDI at the lateral tricuspid annulus. RVFAC was calculated as follows: RVFAC = (RV diastolic area-RV systolic area)/RV diastolic area×100%. RV diastolic area and RV systolic area were obtained from the two-dimensional apical 4-chamber view. The RVMPI is the ratio of the isovolumic time and the ejecting time, which was measured in the same pulsed TDI. The isovolumic time was calculated by subtracting the ejecting time from the tricuspid closure time. The ratio of RV transverse diameter to LV transverse diameter was measured at the base in the end-diastole using the apical 4-chamber view.2; matrix, 150×256 pixels; pixel size, 1.9×1.3; slice thickness, 6 mm; slice distance, 4 mm). The endocardium and epicardium outline of RV and LV were drawn manually using Argus software  by an experienced radiologist to obtain volumes of RV and LV.CMR was performed on a Siemens 1.5 T Sonata system , and phase offset errors was corrected by simultaneous ECG recording. Short-axis cine images including the whole LV and RV from apex to base were acquired by the gradient-echo pulse sequence (True-FISP by Siemens) .Descriptive data for continuous variables with Gaussian distribution were presented as means ± standard deviation. Continuous variables were tested for adherence to a normal distribution with the Kolmogorov-Smirnov method. Pearson’s correlation coefficients were calculated to analysis the association of interesting parameters. Multivariate linear regression analysis was carried out to explain the role of echocardiographic parameters in predicting RVEF. Statistical significance was defined as 2. The subtypes of PAH were, idiopathic PAH 24 patients (80%); PAH associated with connective tissue diseases, 5 patients (16.7%); hereditary PAH, 1 patient (3.3%). The mPAP was 58±16 mmHg and PVR was 1168.5±509.4 dyn·s·cm−5. The cardiac index measured by thermodilution method was 2.39±0.98 L/min/m2. The data of echocardiography and CMR are presented in Demographic, clinical and hemodynamic data of the thirty patients enrolled are shown in r = 0.440, P = 0.015; S’, r = 0.444, P = 0.016; RVFAC, r = 0.416, P = 0.022; IVA, r = 0.600, P = 0.001; RVETD/LVETD, r = −0.649, P<0.001). However, RVMPI had no significant correlation with RVEF .Correlations between echocardiographic parameters and CMR-derived RVEF were shown in r = −0,615, P<0.001; S’, r = −0.557, P = 0.002; RVFAC, r = −0.454, P = 0.012; RVETD/LVETD, r = 0.543, P = 0.002). Moreover, TAPSE , IVA  and RVETD/LVETD  had significant relationships with mRAP. TAPSE, RVFAC and RVMPI showed significant correlations with mPAP.Correlations between echocardiographic parameters and hemodynamic parameters are presented in P = 0.043 and P = 0.015)  . The modSeveral echocardiographic parameters have been reported to assess the RV function and hemodynamics of pulmonary circulation. However, the value of these parameters remains controversial. In the present study, we used echocardiography and CMR to assess RV function and structure in PAH patients. We systemically analyzed the correlations between the echocardiograpic parameters and RV function as well as the hemodynamics, which may provide reference for comprehensively assessing the severity of PAH patients.Despite several studies have validated the value of some echocardiographic parameters in assessing RV function, Among the six echocardiographic parameters, TAPSE, S’, RVFAC, IVA and RVETD/LVETD correlated significantly with RVEF. However, after adjusting for the hemodynamics including mRAP, mPAP and PVR, multivariate regression analysis indicated that IVA and RVETD/LVETD were the only two independent predictors of RVEF. Unaffected by pre−/after-load, et al reported that TAPSE and S’ (r = 0.86 and r = 0.63) significantly correlated with RVEF derived from CMR, et al, PVR of the patients were lower than that of the population in our study and the RV function of were relatively better (with RVEF of 38%±11% vs. 27%±12%). The differences may be due to the heterogeneity of patients included. With regard to the dilated RV in PH patients, circumferential contractility may also contribute a lot to RVEF. A CMR study by Kind et al reported that transverse wall movements provided important information of RV function in PH patients, in which TAPSE measured by CMR also had relatively weak relationship with RVEF (r = 0.458). Both TAPSE and S’ can reflect the longititudinal systolic function of the RV. TAPSE from M-mode echocardiograph has been reported to significantly correlate with RVEF derived from radionuclide angiography. Although the RVFAC is a common parameter for assessing RV systolic function, its two-dimensional measuring view can not completely reflect RVEF which is a three-dimensional parameter. Moreover, the hypertrophied RV trabeculae hinder us to distinguish the endocardium clearly in PH patients, therefore, accurate assessment of RVFAC can’t be assured. So the correlation coefficient in this study is moderate as well as the previous study, The RVMPI has been reported to assess the combined systolic and diastolic function, With regards to the hemodynamic data, TAPSE, S’, RVFAC and RVETD/LVETD correlated with PVR significantly, which may provide some information for PH diagnosis and severity evaluation. In line with the previous study, RVMPI showed significant correlation with mPAP, but not PVR. Firstly, echocardiography, CMR and RHC were not performed simultaneously, which may affect accurate comparisons of multiple methods. However, we excluded the patients with unstable conditions during the study period to reduce the bias. Secondly, the significance of imaging data may vary in different stages of PAH. The number of patients in the present study was small, which did not allow us to evaluate the data in patients with different stages.The echocardiographic parameters IVA and RVETD/LVETD can reflect RVEF independently regardless of hemodynamics in patients with PAH. In addition, TAPSE, S’, RVFAC and RVETD/LVETD can also reflect PVR in PAH patients.


Serum phosphate is an independent predictor of cardiovascular morbidity and mortality in patients with chronic kidney disease and the general population. There is accumulating evidence that phosphate promotes arterial stiffening through structural vascular alterations such as medial calcification, which are already apparent in the early stages of chronic kidney disease.To determine the effects of phosphate binding with sevelamer carbonate on left ventricular mass and function together with arterial stiffness in patients with stage 3 chronic kidney disease.A single-centre, prospective, randomised, double-blind, placebo-controlled trial of 120 subjects with stage 3 chronic kidney disease recruited from University Hospitals Birmingham NHS Foundation Trust. Baseline investigations include transthoracic echocardiography and cardiac magnetic resonance imaging to assess ventricular mass, volumes and function, applanation tonometry to determine pulse wave velocity and pulse wave analysis as surrogate measures of arterial stiffness and dual energy x-ray absorptiometry scanning to determine bone density. During an open-label run in phase, subjects will receive 1600 mg sevelamer carbonate with meals for four weeks. They will then be randomised to either continue sevelamer carbonate or receive an identical placebo (60 subjects per arm) for the remaining 36 weeks. Four-weekly monitoring of serum electrolytes and bone biochemistry will be performed. All baseline investigations will be repeated at the end of the treatment period. The primary endpoint of the study is a reduction in left ventricular mass after 40 weeks of treatment. Secondary endpoints are: i) change in aortic compliance; ii) change in arterial stiffness; iii) change in arterial elastance; iv) change in left ventricular systolic and diastolic elastance; v) change in left ventricular function; and vi) change in bone density.ISRCTN35254279.This trial is registered at ClinicalTrials.gov: NCT00806481 and Current Controlled Trials:  The magbled [2) . These ibled [2) .Atherosclerotic diseases such as myocardial infarction only account for a minority of cardiovascular deaths in patients with CKD, the remainder being attributable to congestive heart failure, sudden cardiac death and arrhythmia . These aSerum phosphate is an independent predictor of cardiovascular morbidity and mortality in patients with CKD and withAlthough serum phosphate rises early in the course of CKD, phosphate binders are currently only used in late-stage disease when major abnormalities of calcium and phosphate metabolism are present. By this time it is likely that arterial and ventricular function are already significantly impaired, partly through prolonged exposure of the vascular system to high levels of phosphate. This study aims to examine the effect of phosphate binding with sevelamer on left ventricular mass, markers of arterial stiffness and left ventricular function in early stage CKD.Phosphate binding with sevelamer carbonate will reduce left ventricular mass, improve indices of left ventricular systolic and diastolic function, and reduce arterial and cardiac stiffness in patients with stage 3 CKD.2) established on conventional treatment with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker for at least 3 months before enrolment. GFR will be estimated by the 4-variable Modification of Diet in Renal Disease formula with serum creatinine recalibrated to be traceable to an isotope derived mass spectroscopy method [This is a single-centre prospective, randomised, double-blind, placebo-controlled trial of 120 subjects with stage 3 CKD  with subjects in the supine position. Serial contiguous short axis cines will be piloted from the vertical long axis and horizontal long axis images of the left and right ventricles  in accordance with previously validated methodologies . Analysi3, flip angle 14°, tag grid angle 45° with slice thickness 6 mm and a minimum number of 15 phases per cardiac cycle) with prospective ECG gating as previously described [Dynamic tissue-tagging magnetic resonance imaging allows direct non-invasive assessment of regional systolic myocardial shortening and is a previously validated technique . Spatialescribed . The myoescribed .75) [Pulse wave velocity  will be performed as previously described followin75) . All meaA comprehensive transthoracic echocardiogram  will be performed with the subject in the left lateral decubitus position by a single experienced echocardiographer using second harmonic imaging and an M3S multi-frequency transducer. All parameters will be measured in triplicate and averaged as per the recommendations of the American Society of Echocardiography . AnalysiGreyscale images for 2-dimensional left ventricular strain and strain rate imaging will be acquired in cineloop format in triplicate from the apical 4-, 2- and 3-chamber views and parasternal short axis views at basal, equatorial and apical levels at end expiration at frame rates >70/second for offline analysis using commercially available software . The endocardial border will be manually tracked at end-systole and the software will then generate a region of interest that will be placed over the myocardium. This will enable frame-to-frame tracking of ultrasonic speckles that change position according to surrounding tissue motion throughout the cardiac cycle. Peak systolic velocities, strain, strain rate, rotation and twist will be measured for each myocardial segment in triplicate and averaged.Dual energy x-ray absorptiometry scanning  will be used to assess bone mineral density of the lumbar spine (L1-L4) and both proximal femurs . Scans will be reported by an experienced bone densitometry clinical scientist blinded to clinical data.Following baseline studies all subjects will receive 1600 mg of sevelamer carbonate with meals for 4 weeks during an open-label run-in phase Figure  and leveAt the end of the open-label run-in phase subjects will attend for a second study visit and the following will be repeated: i) office brachial blood pressure and heart rate measurement in triplicate; ii) applanation tonometry to determine aortic pulse wave velocity; iii) applanation tonometry to derive central pressure waveforms from pulse wave analysis; iv) collection of serum and plasma for haematological and biochemical analysis; v) storage of serum and plasma at -80°C for future assay of biomarkers associated with cardiovascular function and calcification; vi) collection of a spot urine sample to determine albumin: creatinine ratio; and vii) 24-hour urine collection for determination of phosphate excretion.Participants will then be randomised by computer assignment to continue 1600 mg  sevelamer with meals or receive an identical placebo for the remaining 36 weeks , will be recorded and followed up for the duration of the study or until resolution. Assessment of adverse events will be performed by the study investigators. All SAEs will be graded and reported to the sponsor. Any suspected unexpected serious adverse reactions will be reported to the sponsor, ethics committee and Medicines and Healthcare products Regulatory Agency. This study has been reviewed and approved by West Midlands Research Ethics Committee. Written informed consent will be obtained from all study participants.The demonstration of an important pathophysiological role for serum phosphate in the development of cardiovascular disease associated with CKD would be crucial in the understanding of this condition and have important implications for treatment. As left ventricular mass and arterial stiffness are prognostically significant markers in CKD, a positive effect would suggest that phosphate lowering in stage 3 CKD with the non-calcium-based phosphate binder sevelamer, in addition to conventional treatment for blood pressure and hypercholesterolaemia, is of prognostic value and would provide a rationale for a large clinical trial with cardiovascular morbidity and mortality as end-points.75: augmentation index corrected to a heart rate of 75 beats/minute; CKD: chronic kidney disease; CMR: cardiac magnetic resonance; DEXA: dual energy x-ray absorptiometry; ECG: electrocardiogram; ESKD: end stage kidney disease; GFR: glomerular filtration rate; PTH: parathyroid hormone; SAEs: serious adverse eventsAix: augmentation index; AIx®), a non-calcium-based phosphate binder currently licensed in Europe for the treatment of hyperphosphataemia in dialysis patients and CKD patients not on dialysis with serum phosphate >1.78 mmol/L, which has been provided free of charge for the purposes of this study. In addition CJF has received lecture and advisory board fees from Genzyme. No employee from Genzyme or any medical writers have been involved in the preparation of this manuscript.The sponsor for this trial is University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. This investigator-led study is funded through an unrestricted educational grant from Genzyme Corporation, Cambridge, Massachusetts. Genzyme Corporation manufactures sevelamer carbonate (RenvelaCJF, JNT, RPS and CDC all contributed to the design of the study, the drafting of the protocol and this manuscript. CDC will acquire the majority of the data. All authors will be involved in statistical analysis and data interpretation. All authors have read and approved the final version of the manuscript.