Stress cardiomyopathy is a condition of chest pain, breathlessness, abnormal heart rhythms and sometimes congestive heart failure or shock precipitated by intense mental or physical stress.A 64-year-old male with a known diagnosis of moderate-to-severe aortic stenosis and advised that valve replacement was not urgent, presented with acute pulmonary edema following extraordinary mental distress. The patient was misdiagnosed as having a "massive heart attack" and died when managed by a traditional protocol for acute myocardial infarction/coronary artery disease, irrespective of his known aortic stenosis.Intense mental stress poses a considerable risk, particularly to patients with significant aortic stenosis. As described here, it can precipitate acute pulmonary edema. Importantly, effective management of acute pulmonary edema due to stress cardiomyopathy in patients with known aortic stenosis requires its distinction from acute pulmonary edema caused by an acute myocardial infarction. Treatment options include primarily urgent rhythm and/or rate control, as well as cautious vasodilation. Stress cardiomyopathy or "myocardial stunning" is a condition precipitated by severe physical or emotional stress which was first identified in the 1990s . The resAortic stenosis (AS) is the most common valvular heart disease . It affeThe case involves a 64-year-old male scientist with a diagnosis of moderate-to-severe aortic stenosis (AS) and mild-to-moderate aortic regurgitation, but no signs and symptoms of congestive heart failure, and no history of myocardial infarction (MI), or coronary artery disease (CAD). The patient had normal blood pressure and was taking no medications. His AS was monitored by serial echocardiograms , the last of which showed a mean transvalvular gradient of 40 mm Hg and a LV end-systolic dimension of 47 mm. The last cardiology evaluation noted that the patient was fairly active but "may be beginning to get mildly symptomatic." He started to notice chest pressure during certain exertion which was promptly relieved by rest and "could be angina." The patient was told that he should not go jogging, that he was near the point where he should consider AVR, but that the AVR "was not urgent". Two months later, the patient became very distressed and angry seeing a family member hurt by outrageous, unlawful conduct. Within about one hour of this stressful event, while engaging in a sedentary activity, he suddenly experienced severe shortness of breath and began to cough up frothy pink sputum. First responders and emergency physicians were informed that the patient had AS and was just extremely upset. In the ambulance, the patient received oxygen, morphine sulfate (10 mg), furosemide (100 mg) and sublingual nitroglycerin. On presentation in the emergency department (ED) about two hours after the extraordinary mental distress began, the patient was alert, had chest rales, a pulse of 123 beats/min, a blood pressure of 121/73 mm Hg, and a respiratory rate of 28-32. His chest X-ray indicated pulmonary edema. During the first 25 minutes in the ED, as he received more nitroglycerin (as paste twice to the chest), another 2 mg morphine sulfate, 2 mg midazolam, and was intubated for ventilation, vigorous diuresis occurred and the patient's initially normal blood pressure plummeted to <70 mm Hg, systolic. At that point, the ECG also showed that the patient had developed atrial fibrillation (AF) with a rapid ventricular rate of 124 beats/min. The patient was started on i.v. dopamine (10 ug/kg/min through most of the next hour). His heart rate increased to148 beats/min, and blood pressure rose to 80-100 mm Hg but then fell again. Several attempts of cardioversion with shocks of 100, 200 and 300 joules, respectively,  were begun only 40 minutes after AF was identified, and the patient's condition had worsened considerably. Subsequent administration of digoxin (0.25 mg i.v.) and procainamide (1 g i.v. over 20 min) slowed the ventricular rate to 125 beats/min and raised the blood pressure only briefly to 96/62 mm Hg. Cardioversion attempts  were continued, but the patient remained in AF with ventricular tachycardia of 120 beats/min and worsening hypotension . After a fourth 360 J shock no palpable pulse was noted. After 25 min of CPR including four ampoules of epinephrine, each followed by a further shock of 360 J, which resulted in no rhythm, ventricular fibrillation and agonal rhythm, all resuscitation attempts were terminated. The medical chart summary was that the patient had died from a massive AMI. Yet, cardiac enzymes were negative and the autopsy confirmed aortic stenosis as the cause of death with a bicuspid, heavily calcified aortic valve, left ventricular hypertrophy and moderate dilation, focal pulmonary hemorrhages, primarily mild CAD, no evidence of a recent MI, nor any other major abnormalities.The very sudden onset of severe dyspnea and cough producing frothy pink sputum about one hour after the patient became extremely upset, as well as all the evidence from his clinical evaluations before and shortly thereafter, strongly indicate that the acute pulmonary edema was precipitated by the preceding emotional trauma and the result of stress cardiomyopathy. Normal cardiac enzymes and the autopsy findings ruled out any AMI.Irrespective of the patient's known preexisting AS, he was managed primarily with oxygen therapy, morphine sulfate, large doses of both diuretic and nitrates, followed by inotropes. Unfortunately, most of these conventional interventions were not appropriate or beneficial. Current evidence does not support morphine in the treatment of acute pulmonary edema/acute decompensated heart failure . Large dAnother concern is that electrical cardioversion was delayed for some 40 minutes after AF was positively identified, and medical rhythm/rate control even longer while the patient's condition steadily deteriorated. Prolonged infusion of dopamine, started when the patient became hypotensive, would not be expected to improve his hemodynamic condition. The thickened left ventricle (LV) in AS, which has a low or diminished contractile reserve, can hardly be pushed by inotropes to contract more forcefully, while both the subendocardial perfusion (due to the ventricular tachycardia) and the LV filling pressure (due to prior excessive diuresis and AF) are substantially inadequate. Moreover, when an emotional trauma precipitated the congestive heart failure by flooding the system with catecholamines, the high levels of endogenous epinephrine, norepinephrine and dopamine have been shown to persist for many hours. Thus, more dopamine , may amplify (not correct) the precipitating factors and exacerbate the heart failure.According to the general ACC/AHA Guidelines for the Management of Valvular Heart Disease, the cornerstones in the management of acute pulmonary edema in patients with underlying AS should be urgent rhythm and rate control, and vasodilation for decongestion of the lungs . However1. In a patient with known AS, paramedics should start respiratory support, but only cautiously administer nitroglycerine, diuretic and, for high blood pressure, angiotensin converting enzyme (ACE) inhibitors.2. If the pulmonary edema is associated with recent onset AF, or AF develops in the ED, prompt electrical cardioversion to restore normal sinus rhythm and slow the ventricular rate is mandatory. Both AF and a rapid ventricular rate have especially adverse effects in patients with AS. AF can drastically reduce the pre-load, depress pump function and worsen the acute heart failure, since the filling of the hypertrophic LV is up to 40% dependent on proper atrial contractions. Concurrently, AF increases the left atrial and pulmonary venous pressure which exacerbates the pulmonary edema.3. If the pulmonary edema is associated with severe tachycardia , pharmacologic rate (and rhythm) control is essential in AS. Tachycardia and shorter diastolic perfusion time can cause sustained subendocardial ischemia in a hypertrophied heart with reduced coronary blood flow and limited coronary vasodilator reserve. Subendocardial ischemia in turn can trigger arrhythmias, lead to LV diastolic failure and compromise systolic function. An optimal strategy for the medical control of rapid ventricular rates due to metal stress in AS patients has yet to be defined, but drugs to consider may include the following:(a) There is a rationale for cautious use of intravenous, short-acting beta-adrenergic blocking agents, such as esmolol and landiolol, if excessive adrenergic stimulation related to mental stress is the suspected mechanism for the tachycardia or tachyarrhythmia.Esmolol, an ultra short-acting  and relatively cardioselective beta blocker, has been shown (at 25-300 ug/kg/min) to rapidly slow the heart rate in patients with AF, to effectively relieve chest pain due to acute myocardial ischemia, and to achieve a clinical significant reduction in heart rate (20% or <100 beats per minute) in about 70% of patients, and a conversion to sinus rhythm in about 15%. The principle adverse effect of esmolol is hypotension due to a decrease in cardiac output. But even tachyarrhythmias associated with congestive heart failure, where beta blockers are otherwise contraindicated, may be relatively safely managed with esmolol by starting with a small dose, slowly increasing it while the patient is closely monitored, and decreasing/discontinuing the infusion when complications arise which tends to reverse them Landiolol, a short acting selective beta-1 adrenergic blocker, has been reported to effectively control tachycardia in patients during surgery including one patient with severe aortic stenosis and, in one case, to convert AF to sinus rhythm ,8. Beta-(b) Amiodarone (single bolus or short term infusion) effectively treats many cardiac arrhythmias and may be an option for fast heart rate control when other measures fail -12. Alth4. For decongestion of the lungs in patients with AS, vasodilators should be preferentially used over diuretics to maintain a sufficiently elevated left ventricular filling pressure and produce an adequate forward stroke volume and cardiac output. Vasodilation with intravenous nitroprusside has been reported to rapidly and significantly increase the cardiac index in critically ill patients with severe AS and congestive heart failure as long as they are not hypotensive ,14 PartiAdministration of both a short acting beta blocker and nitroprusside in combination rather than sequentially may be more effective, if the acute pulmonary edema coexists with acute AF, given the interaction between the two.This case illustrates that extraordinary psychological stress can precipitate acute pulmonary edema in patients with advanced AS and, like physical exertion, poses a significant risk to them. These patients and their families need to be warned of this risk to avoid it as much as possible. The differentiation between stress cardiomyopathy and AMI- caused acute pulmonary edema is critically important in patients with known AS for effective emergency care to alleviate symptoms and stabilize them for AVR. Potential treatment options for acute pulmonary edema due to stress cardiomyopathy in such patients include urgent electrical cardioversion, intravenous, short acting beta blockers, or amiodarone for rhythm and/or rate control, as well as cautious vasodilation with intravenous nitroprusside, invasively monitored to decongest the lungs and improve LV performance. By contrast, aggressive diuresis and preload reduction must be avoided to prevent intractable hypotension and hypoperfusion. Inotropes like dopamine are not indicated after emotional stress and catecholamine surge.AS: aortic stenosis; AVR: aortic valve replacement; AF: atrial fibrillation; MI: myocardial infarction; CAD: coronary artery disease; ED: emergency department; LV: left ventricle.Written informed consent was obtained from the widow for the purpose of publication of the manuscript. A copy of the written consent is available for review by the editor-in-Chief of this journal.The author declares that she has no competing interests.


Tako – tsubo like syndrome  is an unusual cardiomyopathy with an high incidence in Japanese population of female sex, following an emotional stress. The clinical features , and the electrocardiographic changes (negative T wave and persistent ST elevation in anterior leads), are suggestive of an acute myocardial infarction; nevertheless the coronary angiography show coronary arteries without lesions and the ventriculography show specific segmental dysfunction. In the literature there are many reports of typical left ventricular ballooning ; due to the rarity of the atypical localizations  many authors think they are different physiopatologic entity.We report a case of 50 – years old woman, with a family history of ischeamic cardiomyopathy but with no additional cardiovascular risk factors, who arrived to emergency department with a recent episode of chest pain (about 30 minutes) with electrocardiographic and echocardiographic features suggested of a inferior ST elevation myocardial infarction. Coronary angiography showed coronary arteries without atherosclerotic lesions; ventriculography showed an inferior dysfunction.This data can suggest for an atypical form  of left ventricular ballooning involving the inferior wall (never described in the literature), not preceded by any emotional or physical stress. The follow – up performed by transthoracic echocardiography (2 months later) revealed a complete regression of wall motions abnormalities. The left ventricular "apical ballooning" syndrome, also known as "Tako – Tsubo like syndrome", has recently been the subject of numerous studies and reports in the literature, to the point that the term "stress-induced cardiomyopathy"  has beenThe incidence of the pathology is estimated to be approximately around 1% – 2% among all patients who come under cardiological attention for acute ischemic events ; according to a recent statistic by the American Heart Association, out of 732,000 yearly dismissals of patients with a primary diagnosis of acute myocardial infarction, a number varying between 7,000 and 14,000 patients may present stress-induced cardiomyopathy [The physiopathological motive seems to be linked to the plasmatic release of catecholamines as a result of intense emotional and/or physical stress with their consequent direct damage in terms of the metabolism of cardiac myocytes; high levels of catecholamines reduce myocyte activity through an overload of calcium mediated by cyclic adenosinmonophosphate; catecholamines are also sources of free radicals derived from oxygen and, in animal models, by interfering with the transmembrane transport of sodium and calcium, they cause a myocyte dysfunction, increasing the concentration of intracellular calcium ,6.In 2006 the American Heart Association included "stress-induced cardiomyopathy" in the classification of cardiomyopathies as a "primitive and acquired cardiomyopathy" which can involve the entire extension of the left ventricle and no longer just the apex, as described initially[We describe a case of ventricular ballooning localized at the level of the inferior wall in a patient who came to our observation in the absence of emotional and physical stresses identifiable by the anamnesis, chest pain and electrocardiographic alterations characteristics for acute ST elevation myocardial infarction (STEMI).A 50-year old woman, known to have surgically treated congenital hydrocephalous, with a family history of ischemic cardiopathy but with no additional cardiovascular risk factors, without a recent major psychological or physical stresses, was admitted to our Emergency Department for prolonged chest pain felt while at rest, continuos and not irradiated, lasting for about 45 minutes and partially reduced spontaneously upon arrival at the hospital. The physical examination did not yield any pathological findings; blood pressure was 100/70 mmHg. Entry electrocardiogram showed the presence of sinusal rhythm and ST elevation in the inferior leads and light ST depression in lateral  and absence of valve pathologies of relevance. The first hematochemical exams showed a significant increase in cardio-specific enzymes . After the start of intravenous medical therapy with nitrates, sodic heparin (5000 U in bolus and 1000 U/hour), inhibitors of the glycoprotein IIB/IIIa (abciximab) and orally with beta blocker (atenolol 100 mg), atorvastatin (40 mg) and clopidogrel (300 mg) the patient was subjected to a urgent coronary angiography.The procedure showed epicardic coronaries free of lesions Figure ; howeverIn the literature, in recent years, there have been numerous reports of patients with transitory dysfunction of the left ventricle in relation to physical stress or to episodes of important psychic stress ,8. The fAs early as 2002, Karisu et al highlighHowever, etiology does not seem altogether clear; Karisu et al demonstrated, through the histological analysis of the myocardial muscle tissue, performed through endomyocardial biopsy, the presence of focal areas of myocytolysis and of infiltration by mononucleated cells and free connective tissue ; moreoveThe most creditable etiology and physiopathology hypothesis seems to be that as a result of mental and/or physical stress there is an increase in the plasmatic release of catecholamines  and that said plasmatic concentration is able to determine a direct effect on myocyte metabolism. High levels of catecholamines reduce myocyte activity  through However, our case completely deviate from the characteristics just described, both in the anamnestic absence of evident psycho-physical stress and in the localization of the ventricular ballooning .The typical apical localization of the ballooning is not quite clear: it seems to be linked to a greater response to the adrenergic stimulus at the level of the apex of the myocardium (the norepinephrine content at the apex is lower than at the base); moreover, at the human heart level there is a heterogeneous distribution of nervous terminations. The ventricular apex may be no more vulnerable to the adrenergic stimulus than the medium – ventricular region and the base; this physiological variation of the regional vulnerability of the left ventricle could be responsible for the different localizations.An additional alternative, recently proposed , which cThe current common international scientific opinion agrees that the "ventricular ballooning syndrome" has the same origin regardless of localization, therefore we can speak of "all sides of the same coin". However, there are some differences between the clinical characteristics of patients with non apical ballooning and those with apical ballooning: the former present more intense heart failure and absence of electrocardiographic alteration. The peculiarity of our case regards, in addition to the atypical and rare inferior localization, above all the absolutely abnormal manifestation (STEMI), with no psycho – physical stress.In conclusion we described and explained a rare case of atypical left ventricular ballooning involving the inferior wall presented to our attention mimicking an acute inferior myocardial infarction.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor – in Chief of this journal.The authors declare that they have no competing interests.All authors have made substantial contribution to concept this case report.


Biventricular pacing (BiP) is an effective treatment in systolic heart failure (HF) patients with prolonged QRS. However, approximately 35% of the patients receiving BiP are classified as non-responders. The aim of this study is to evaluate the acute effects of VV-optimization on systolic heart function.Twenty-one HF patients aged 72 (46-88) years, QRS 154 (120-190) ms, were studied with echocardiography, Tissue Doppler Imaging (TDI) and 3D-echo the first day after receiving a BiP device. TDI was performed; during simultaneous pacing (LV-lead pacing 4 ms before the RV-lead) and during sequential pacing (LV 20 and 40 ms before RV and RV 20 and 40 ms before LV-lead pacing). Systolic heart function was studied by tissue tracking (TT) for longitudinal function and systolic maximal velocity (SMV) for regional contractility and signs of dyssynchrony assessed by time-delays standard deviation of aortic valve opening to SMV, AVO-SMV/SD and tissue synchronization imaging (TSI).The TT mean value preoperatively was 4,2 ± 1,5 and increased at simultaneous pacing to 5,0 ± 1,2 mm , and at best VV-interval to 5,4 ± 1,2 . Simultaneous pacing achieved better TT distance compared with preoperative in 16 patients (76%). However, it was still higher after VV-optimization in 12 patients 57%. Corresponding figures for SMV were 3,0 ± 0,7, 3,5 ± 0,8 , and 3,6 ± 0,8 . Also dyssynchrony improved.VV-optimization in the acute phase improves systolic heart function more than simultaneous BiP pacing. Long-term effects should be evaluated in prospective randomized trials. Chronic heart failure (CHF) is perhaps the most common reason for in-hospital health care utilization and costs are very high. Despite drugs such as RAAS-blockers, beta-blockers, diuretics and aldosterone-antagonists which all have positive prognostic effects these patients suffer from poor quality of life (QoL) and a readmission rate as high as 30% within 90 days -5.Cardiac Resynchronization Therapy (CRT) is established as an effective treatment in systolic heart failure (HF) patients with prolonged QRS being in functional class (NYHA) III-IV despite optimal medical treatment. CRT has been shown to improve heart function, QoL, morbidity and mortality -10. HoweWhen giving effective drugs as RAAS- and beta-blockers it is obvious that dosages should be individualized and slowly optimized to achieve best effects and to avoid adverse effects. In CRT, however, it seems uncommon to individualize and optimize programming of the device and there are so far surprisingly few long-term randomized studies on this issue. Patients with CHF in NYHA-class III or IV have very high one- year mortality, 30-50%, which should make attempts to optimize the CRT device high priority. In the land-mark study CARE-HF , AV-delaThe aim of this study was to evaluate the effect of VV-optimization during the first day after implantation of a CRT device on systolic heart function and signs of dyssynchrony.We enrolled 21 consecutive heart failure patients with standard criteria for biventricular pacemaker treatment. All patients had reduced systolic left ventricular (LV) function with an ejection fraction (EF) below 35%, QRS - duration >120 ms and New York Heart Association (NYHA) function class III-IV despite optimal medical treatment. Twenty-one patients were on ACEi/ARB:s, 21 on diuretics and 19 were on beta blockers. Mean age was 72 (range 46-88) years and 18 patients were of male gender  echocardiography was acquired in three apical views using a vivid 7 or 5 (the later for 3-D echocardiography only) system , with a 2.5 MHz probe. Three consecutive beats were registered and mean values were used for further analysis. Analyses were made off-line . Systole was defined as the ejection time from the aortic valve opening (AVO) to the aortic valve closure (AVC). The 16 segments LV-model of the American Society of Echocardiography was used for orientation . Base anDyssynchrony was measured by 2 different methods AVO-SMV/SD  where the time AVO-SMV max was calculated in ms for each of the 14 segments. A mean value with a standard deviation (SD) was calculated, the SD given as a measure of dyssynchrony. We also used Tissue Synchronization Imaging (TSI). The TSI start was set at the AVO and the TSI end at the AVC in order to focus only on the systolic phase. A cut-off value of 65 ms was chosen prospectively. All the TDI analysis were performed twice by the same investigator and the mean of the two measurements was used. Intra-variability was fairly low. The coefficient of variation for TSI analysis was 3,0%.Transthoracic 3D Echo was performed using a 2,5 MHz transducer mounted in a handheld rotation device. The cardiac images were recorded from the apex during end-expiratory apnoea within one breath hold, whereby the need for respiratory triggering was abolished. Imaging was performed using tissue harmonic mode using coaxial rotation from the apical position and ECG-triggered recording where each R-wave initiated a 30° stepwise rotation of the transducer. A total of six scanning planes obtained by 30° stepwise rotation of the transducer covered the entire LV. To eliminate disturbances caused by cardiac arrhytmias, only R-R intervals within 20% of the mean were accepted. Ejection fraction was calculated by the formula EDV-ESV/EDV × 100. Body surface area (BSA) was used to calculate EDVi and ESVi of the LV. All examinations were stored on magnetic optical discs for later off-line analysis.®, Medtronic) implanted transvenously with a lead in the right atrium and the RV lead positioned in the middle of the ventricular septum. The LV lead was positioned by identifying the sinus coronarius in the right atrium and implanted in a lateral epicardial vein in all patients except for three who had anterio-lateral position of the LV lead. The latter location was chosen due to anatomy in two patients and due to a high threshold in the lateral position in one patient.All patients received a cardiac resynchronization therapy (CRT) device (Insync IIIThe day after implantation the patients were examined with extensive Tissue Doppler Echocardiography (TDE). TDE was performed after 10 minutes of pacing at each VV- interval during simultaneous pacing LV lead . After this examination the atrium ventricular delay was optimized by using the longest achievable (the iterative method) left ventricular filling time .Mean values ± SD are given unless otherwise stated. For within individual changes paired parametric student's t- tests were used when variables showed normal distribution and non-parametric tests, Wilcoxon matched pairs, when not. We used multiple linear regression to explain the differences in LV-endsystolic diameter and in turn as dependent variables age, gender, etiology, QRS-duration, LV lead location, SMV, TT, AVO-SMV/SD and TSI were used as possible predictors. Instead of using a step-wise method for finding the best combination of predictors we used the method of best subsets. The criterion used for ranking those subsets was "Mallows Cp". A p value < 0.05 was considered statistically significant.Preoperative SMV was 3.0 ± 0.7 and at simultaneous pacing it was 3.5 ± 0, 8 cm/sec p < 0, 01)(+18 ± 17%). At best VV-interval  it increased to 3.6 ± 0,8  an increase of 23 ± 20% (range 0.5-70.1%) which preoperatively was 4.2 ± 1,5 mm and increased to 5.0 ± 1.2 mm (P < 0.05)(+29 ± 47%) at simultaneous pacing. At the best VV-interval it increased further to 5.4 ± 1.2 mm (p < 0.001)  compared to preoperative values, TT was better in 16 patients at simultaneously pacing compared with preoperative value. Twelve patients (57%) had still higher TT after VV-optimization compared with simultaneous pacing . However, at best VV-interval it decreased to 35.0 ± 19.5 ms  compared with simultaneous pacing. Compared to preoperative values, AVO-SMV/SD was better (lower) in 8 patients. Eighteen patients (86%) had less dyssynchrony after VV-optimization compared with simultaneous pacing . After VV-optimization there were 3.6 ± 2.3 affected segments  and statistically significantly less compared with simultaneous pacing (p < 0.001). Compared to preoperative values, TSI was better in 8 patients at simultaneously pacing and increased in 10 patients. At the best VV-interval, 16 patients (76%) had less dyssynchrony after VV-optimization compared with simultaneous pacing  and LVESd decreased 7.3 mm to 53.0 ± 9.5 mm (p < 0.05). LVEDVi and LVESVi decreased 27.1 and 27.6 ml respectively, however not statistically significant. EF changed 4.8% to 30.8 ± 9.4%, n.s. Preoperative values are given in Table A multiple linear regression analysis was performed to see which variables explained the changes in LV dimensions. Examined variables were age, gender, etiology, QRS-duration, LV lead location, SMV, TT, AVO-SMV/SD and TSI. The only variables explaining changes in LV dimensions were SMV, AVO-SMV/SD and TSI.The main finding in this study is that approximately 2 of 3 patients with chronic heart failure (CHF) receiving cardiac resynchronization therapy (CRT) improve their systolic heart function in the acute phase more with sequential biventricular pacing than with simultaneous biventricular pacing. This when systolic function is expressed as regional contractility, longitudinal motion and dyssynchrony measured by Tissue Doppler Imaging echocardiography. Choosing sequential pacing, the best choice in this study turned out to be pacing the LV lead before the RV lead and of tested programming LV lead 20 ms before RV lead turned out to have best effect on systolic function.Bearing the serious prognosis of these HF patients in mind it should be obvious trying to get as much beneficial effect as possible from the CRT device through individual optimization. The highest individual increase in this study was 187% of the TT value  compared with 75% at simultaneous pacing. Similar results have been achieved by others .An important question is whether to VV-optimize, AV-delay optimize or to do both or to do neither.It's difficult to say for sure what is right since there today are too few long-term randomized controlled trials (RCT's) to give a clear answer to this question. There are mainly three types of dyssychrony which are to be treated with CRT; inter-ventricular and intra-ventricular (both affected by VV optimization) and atrio-ventricular (affected by AV-delay optimization). The inter-ventricular mechanical delay (IVMD), is defined as the time difference between the onset of forward flow in the LV outflow tract and RV outflow tract >40 ms and intra-ventricular as when the time difference between regional myocardial maximal velocities exceed 65 ms. Atrio-ventricular dyssynchrony (LVFT/R-R) is considered present if the left ventricular filling time (LVFT) measured from the mitral valve Doppler in-flow signal is <40% of the cardiac interval (R-R). The usual proportion of these different types of dyssynchrony are 60%, 80% and 30% in such HF patients with reduced ejection fraction and prolonged QRS -18. MoreThus, the figures presented in this study strongly suggest an individualized approach to optimization of the CRT device since some patients might benefit from VV-optimization, others from AV-delay optimization and others from both. How reverse remodelling influences on dyssynchrony and long-term effects of device optimization should be studied in future RCT's. Two published RCT's have however not demonstrated any beneficial effects of VV optimization on LV dimensions, functional class or QoL ,20.There are many ways to measure hemodynamik effects of device programming.Echocardiography measuring stroke volume by left ventricular outflow tract (LVOT) VTI is perhaps most used. We prefer the TDI method, since we are used to it and therefore find it a time efficient method to find the most appropriate programming with regard to it's relation with regional contractility (dP/dt) and longitudinal function. This can also be achieved by visual examination only, without the need for measurements Fig . Thus, aA major limitation of this study is the lack of randomization and the small patient number. Designing this trial again we would have included more patients and performed a randomization to assess the long-term effects of VV-optimization added onAV-delay optimization on LV function, NYHA-class and QoL. However, we believe this pilot study is important for highlighting the potential individual effect of VV-optimization in HF patients with prolonged QRS. Thus, even if this study is small and contains no long-term data, VV-optimization the first day after CRT implantation the study highlights the potential benefits of such strategy.The PROSPECT (Predictors of response to cardiac resynchronization therapy) trial, an observational study, was somewhat disappointing concerning the value of measuring dyssynchrony . This waThus it is important to perform a solid echocardiography examination not only to assess LV systolic function and degree of dyssynchrony but also to avoid other causes of heart failure, which shouldn't be treated with biventricular pacing, as valve diseases and non-viable myocardium. The latter can be done by a low-dose dobutamin stress-echocardiography examination.Approximately 2 of 3 patients with chronic heart failure receiving cardiac resynchronization therapy improve their systolic heart function in the acute phase more with sequential biventricular pacing than with simultaneous biventricular pacing. Choosing sequential pacing, the best choice is to pace the LV lead before the RV lead and of tested programming LV lead 20 ms before RV lead turned out to have best effect on systolic function. The long-term clinical importance of these findings should be studied further.This study was supported with grants from the Karolinska Institutet and Medtronic.ME has received honoraria and research support from Medtronic.MR and TS have no conflicts of interest to declare.ME: Made substantial contributions to conception and design, acquisition, analysis and interpretation of data, mainly responsible for drafting the manuscript.MR: acquisition, analysis and interpretation of data. TS: acquisition, analysis and interpretation of data. All authors have read and approved the final manuscript.


Myocardial infarction causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biomarkers have been used to assist with timely diagnosis, while an increasing number of novel markers have been identified to predict outcome following an acute myocardial infarction or acute coronary syndrome. This may facilitate tailoring of appropriate therapy to high-risk patients. This review focuses on a variety of promising biomarkers which provide diagnostic and prognostic information.Heart-type Fatty Acid Binding Protein and copeptin in combination with cardiac troponin help diagnose myocardial infarction or acute coronary syndrome in the early hours following symptoms. An elevated N-Terminal Pro-B-type Natriuretic Peptide has been well validated to predict death and heart failure following a myocardial infarction. Similarly other biomarkers such as Mid-regional pro-Atrial Natriuretic Peptide, ST2, C-Terminal pro-endothelin 1, Mid-regional pro-Adrenomedullin and copeptin all provide incremental information in predicting death and heart failure. Growth differentiation factor-15 and high-sensitivity C-reactive protein predict death following an acute coronary syndrome. Pregnancy associated plasma protein A levels following chest pain predicts risk of myocardial infarction and revascularisation. Some biomarkers such as myeloperoxidase and high-sensitivity C-reactive protein in an apparently healthy population predicts risk of coronary disease and allows clinicians to initiate early preventative treatment. In addition to biomarkers, various well-validated scoring systems based on clinical characteristics are available to help clinicians predict mortality risk, such as the Thrombolysis In Myocardial Infarction score and Global Registry of Acute Coronary Events score. A multimarker approach incorporating biomarkers and clinical scores will increase the prognostic accuracy. However, it is important to note that only troponin has been used to direct therapeutic intervention and none of the new prognostic biomarkers have been tested and proven to alter outcome of therapeutic intervention.Novel biomarkers have improved prediction of outcome in acute myocardial infarction, but none have been demonstrated to alter the outcome of a particular therapy or management strategy. Randomised trials are urgently needed to address this translational gap before the use of novel biomarkers becomes common practice to facilitate tailored treatment following an acute coronary event. Coronary artery disease (CAD) and its end result, myocardial infarction (MI) continue to be a significant cause of mortality and morbidity in the western world. Over the past 50 years, it has become clear that the cascade of thrombotic events following atherosclerotic plaque rupture causes occlusion of the coronary artery, interrupting blood supply and oxygen to myocardium thus resulting in infarction. Myocardial necrosis following infarction is followed by heart failure, myocardial rupture or arrhythmias. Early treatment of myocardial ischaemia to prevent necrosis with treatments such as fibrinolysis, coronary artery bypass grafting and percutaneous coronary intervention have improved outcome .Over time it has become clear that in order for such treatments to be of maximal benefit, timely diagnosis is important. Here, biomarkers become important, to help us improve our diagnostic accuracy of the disease, as treatments are not without risk. Furthermore, biomarkers also provide prognostic information about the disease, which then aids clinicians in deciding how aggressively they need to treat the disease.th percentile of the upper reference limit) and one of 1) symptoms of ischaemia, 2) electrocardiogram (ECG) changes of new ischaemia, 3) new pathological Q waves or 4) imaging evidence of new loss of viable myocardium.Biomarkers are measurable and quantifiable biological parameters which serve as indices for health and physiology assessments . This inBoth the ECG and cardiac troponin are biomarkers, but the focus of this review will be on serum proteins/markers which have become increasingly important to improve our diagnosis of myocardial infarction, in some cases identifying people at risk of having an infarct and in others to predict long term prognosis following an actual event.A good biomarker is something that is easily measured and can be used as a surrogate marker for disease and its severity . For insSome of these newer biomarkers and their relationship to various pathophysiological processes are depicted in Figure Two well known biomarkers in use for diagnosis of acute myocardial infarction are Creatine-Kinase-MB isoform and Cardiac Troponin. In 2000, Cardiac Troponin replaced CK-MB as the biomarker of choice for diagnosing a myocardial infarction . Troponiwashout phenomenon. Troponin levels peak at 12 hours, and stay elevated for 10 days or more. Whilst the use of Troponin for diagnosing AMI and risk stratification to aid decision making has revolutionised the management of patients presenting with chest pain, the 12-hour wait for the levels to peak remains the Achilles heel of this biomarker. Newer, more sensitive troponin assays [P = 0.003). In addition, the following two biomarkers may help facilitate early diagnosis of AMI, although neither has been compared with the newer high sensitivity troponin assays.Cardiac troponin level is dependent on infarct size , thus gin assays  have beeCopeptin is the more stable surrogate of arginine vasopressin (AVP), with well-known effects on osmoregulation and cardiovascular homeostasis . Post AMCopeptin can rule out MI earlier in addition to a negative Troponin T test . At the H-FABP is a low molecular weight protein involved in myocardial fatty-acid metabolism . It is aBefore broaching the subject of biomarkers it is important to note that as a result of various randomized control trials and registry studies, various risk factors have been identified and entered into scoring systems that allow a clinician to risk stratify disease . PopularNewly introduced biomarkers should complement and have incremental prognostic value over and above these simple risk scores. It is therefore no surprise that biomarkers providing prognostic information following an acute coronary syndrome reflect the various physiological pathways described in the GRACE score . Currently, the only accepted biomarker affecting a change in management of a patient with an acute coronary syndrome is the cardiac troponin.One of the best known biomarkers of biomechanical stress is the B-type Natriuretic Peptide (BNP). Secreted by the ventricles in response to cardiomyocytes under tension , BNP binNTproBNP/BNP provides incremental information on cardiovascular death at one year in the older population above and beyond GRACE score . On its The TACTICS-TIMI 18 study  randomizLike BNP, ANP has similar neurohormonal effects and has a similar secretory profile post AMI. Prior studies have attempted to accurately measure levels of ANP and N-ANP, with limited success ,40. N-ANGDF-15 is a member of the Transforming Growth Factor Beta cytokine superfamily. It is not normally expressed in the heart, but under episodes of stress  its levels go up in a variety of tissues, including cardiomyocytes. It has an antihypertrophic effect, demonstrated in knockout mice which develop early cardiac hypertrophic growth following pressure overload . GDF-15 These findings were validated in ST-elevation MI (STEMIs)  and prosHowever, GDF-15 is not specific for cardiovascular disorders and has been found to be elevated in a variety of malignancies .ST2 is an IL1-receptor-like protein which was found to be elevated in serum of hearts under mechanical stress . ST2 preP= 0.002). This variable is independent of age, Killip class and past medical history. Plasma concentration of CTproET-1 peaks at Day 2 [Endothelin-1 or the more stable C-Terminal portion of pro-Endothelin-1(CTproET1) has also been found to be predictive of death or heart failure following an AMI . ET1 is at Day 2 .Adrenomedullin was first identified in human phaeochromocytoma cells . It is hThe same study group also investigated Copeptin as a prognostic biomarker. They found that Copeptin predicted mortality or heart failure at 60 days post AMI . In addiFigure vulnerable plaques. It is thought that one of the driving forces causing atheromatous plaques to rupture or erode, causing a cascade of events leading to coronary artery occlusion, is inflammation in the plaques. An elevated C-reactive protein measured in seemingly healthy adults was associated with increased cardiovascular risk [Acute coronary syndromes are caused by lar risk ,82. CRP lar risk -87. Thislar risk . While tP = 0.04) and death  post-MI [One study found that CRP measurements (taken between 12 and 24 hours post event) predicted occurrence of heart failure . A new assay for Human Pentraxin 3 is now available. Human Pentraxin 3 is an isoform which is secreted exclusively in vascular endothelium and therefore may be more specific to the vascular plaque inflammatory activity . It remaLeucocytes play a central role in atherosclerotic plaque rupture -96. MyelOne trial showed that post-acute coronary syndrome MPO levels higher than median predicted future death and MI at one year . It alsoTwo population studies show that MPO (and CRP) in healthy individuals are both associated with future development of CAD ,102.Collectively the current evidence supports the need for further studies into the actual role of MPO, and whether elevated MPO levels in the serum directly correlates with MPO released from circulating neutrophils.PaPPA is a proatherosclerotic metalloproteinase  which isLike CRP, PaPPA is expressed when there is a heavy burden of unstable atheromatous plaque, including in carotid arteries . It alsoThe structural integrity of myocardial Extracellular Matrix (ECM) is dependent on endogenous zinc-dependent endopeptidases known as matrix metalloproteinases (MMP). These enzymes are regulated by tissue inhibitors of metalloproteinases (TIMPs). MMPs may degrade myocardial ECM leading to the development of LV dilatation and heart failure and their inhibition in experimental models of AMI has been associated with reduced LV dilatation and wall stress. Although NTproBNP, TIMP1 and MMP 9 were associated with cardiovascular death, heart failure or both, they were not associated with re-infarction . MMP2 isin vitro, so that preanalytical contributions to variation are minimised to some extent. For example, the midregional epitopes assayed in MRproANP and MRproADM are less susceptible to exoprotease action, and prohormone fragment assays tend to be more stable than assays for the actual hormone .Many of the new biomarkers introduced have enhanced stability Although there are large numbers of emerging novel biomarkers, our understanding of the roles and biochemistry of these various peptides in the disease process is still fairly limited. It is difficult to draw specific conclusions from the current body of evidence regarding the mechanisms through which a biomarker could affect the prognosis. Many of the studies use death or major adverse cardiovascular events as endpoints because they are easy to measure, but either of these endpoints could be a culmination of a variety of pathophysiological processes. As such, currently available biomarkers have not been able to add much to helping us tailor our treatment (over and above Troponin). Randomised trials based on the use of biomarkers to alter therapy would be very informative. Although there is evidence that combining biomarkers may increase the accuracy of the tests, the best combinations for diagnosis or prognosis need to be defined. Some analogies can be drawn from heart failure studies; NTproBNP has been used as a biomarker for diagnosis of heart failure . It doesThere is some evidence that a multi-marker strategy can improve diagnosis, risk stratification and prognostication of patients . Of the ADM: Adrenomedullin; AMI: Acute Myocardial Infarction; ANP: Atrial natriuretic peptide; AVP: Arginine vasopressin; BNP: B-type natriuretic peptide; CAD: Coronary artery disease; CTproET1: C-terminal pro-endothelin 1; CKMB: Creatine kinase MB isoform; ECG: Electrocardiogram; ECM: Extracellular matrix; ET1: Endothelin-1; ETA: Endothelin receptor type A; ETB: Endothelin receptor type B; GDF-15: Growth differentiation factor 15; GRACE: Global registry of acute coronary events study; H-FABP: Heart type fatty acid binding protein; HsCRP: High sensitivity C-reactive protein; IGF-1: Insulin-like growth factor 1; IL-33: Interleukin 33; LV: Left ventricle; LVEF: Left ventricular ejection fraction; MI: Myocardial infarction; MMP: Matrix metalloproteinase; MPO: Myeloperoxidase; MRproANP: Mid regional pro-atrial natriuretic peptide; MRproADM: Mid regional proadrenomedullin; N-ANP: N-terminal pro-atrial natriuretic peptide; NSTEACS: Non-ST elevation acute coronary syndromes; NTproBNP: N-terminal pro-B type natriuretic peptide; PaPPA: Pregnancy associated Plasma Protein A; ROC AUC: Area under the receiver operating characteristic curve; TIMI: Thrombolysis in Myocardial infarction study; TIMP: Tissue inhibitors of metalloproteinases; Trop: TroponinProf. Leong Ng has submitted patents on behalf of the University of Leicester on some of the biomarkers in this review, and has acted as a consultant to and received grants in aid from BRAHMS AG and Unipath PLC in the past. Dr. Daniel Chan has no competing interests to declare.LN recruited the patients in the reported studies, performed the analyses and drafted the manuscript. DC participated in the analyses and drafting of the manuscript and figures.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/8/34/prepub


The incidence of rheumatic mitral stenosis is grossly reduced in India. Still, among heart disease complicating pregnancy, rheumatic mitral stenosis occupies a greater segment. The unique physiological changes in pregnancy and the pathological impact of mitral stenosis over pregnancy and labour are discussed in detail. A multidisciplinary approach in the diagnosis and management reduces the mortality and morbidity during peripartum. The labour analgesia technique and the evidence-based regional and general anaesthesia techniques are discussed at length in this article. Rheumatic heart disease is still a major heart problem associated with pregnancy in India, despite its declining trend. The incidence of rheumatic mitral stenosis was 5.4 per 1,000 school children in 1995,3 RheumatAlthough the physiologic changes in the cardiovascular system appear to begin in the first trimester, these changes continue into the second and third trimesters, when the cardiac output increases by approximately 40% of the pre-pregnant values. The cardiac output increases from the fifth week of pregnancy and reaches its maximum levels by 32 weeks. Cardiovascular changes during pregnancy are summarized in 2 is progressively reduced to 2 cm2, the classical symptoms of mitral heart disease start appearing. Mitral stenosis prevents emptying of the left atrium and subsequent filling of the left ventricle, resulting in decreased stroke volume and decreased cardiac output. Consequent to the fixed cardiac output state, the heart cannot cope up with situations warranting increased metabolic demand or increased blood volume. When the stenosis progresses, the left atrium dilates and the left atrial pressure increases. A pressure gradient develops during diastole between the left atrium and the left ventricle. This pressure gradient is the haemodynamic hallmark of mitral stenosis. Hence, the back pressure on the pulmonary vessels leads to pulmonary congestion and, in severe cases, pulmonary oedema. Longstanding pulmonary venous congestion causes irreversible changes in the vessel wall, leading to chronic pulmonary hypertension.When the normal mitral valve orifice area of 4–6 cmWomen with severe mitral stenosis often do not tolerate the cardiovascular demands of pregnancy. This increased volume load and tachycardia together cause the patients to deteriorate and advance from one New York Heart association (NYHA) class to another. The increased heart rate of pregnancy limits the time available for left ventricular filling, resulting in increased left atrial and pulmonary pressures and an increased likelihood of pulmonary oedema. When the pulmonary capillary pressure exceeds the blood oncotic pressure, pulmonary oedema develops. Atrial fibrillation worsens this scenario and about 80% of the cases of systemic emboli occur in patients with atrial fibrillation.Cardiac decompensation and pulmonary oedema may occur in pregnant women with overt or silent mitral valve stenosis during the second or third trimester. The risk of maternal death is greatest during labour and during the immediate post-partum period. The sudden increase in the pre-load immediately after delivery, due to autotransfusion from the uterus, may flood the central circulation, resulting in severe pulmonary oedema. In addition, there continues to be autotransfusion of blood for 24–72 h after delivery. Thus, the risk of pulmonary oedema extends for several days after delivery. The greaAlthough clinical examination, electrocardiogram and X-ray chest reveal many relevant findings, echocardiography is the standard imaging tool used to assess patients with mitral stenosis. Echocardiography provides information regarding the area of the mitral valve, size of the left atrium, presence of thrombus and the size and function of the left ventricle and right-sided chambers. Doppler examination provides information about the severity of the stenosis, the presence of other associated valve lesions and the degree of pulmonary hypertension . DiagnosThe maternal outcome seems to correlate well with the New York Heart Association (NYHA) functional classification.10 MaternPrior heart failure, arrhythmia, transient ischaemic attack or stroke.A baseline NYHA III class or more or cyanosis.Systemic ventricular dysfunction .Pulmonary hypertension .Left heart obstruction.2, Doppler jet velocity 4 m/s).· Severe aortic stenosis Warfarin from 12 to 36 weeks (maintain INR 2.5–3.0)SC/IV heparin after 36 weeksTherapy with low-molecular weight heparin (LMWH) instead of unfractionated heparin is gaining popularity. Although an “anti Xa” activity is used to monitor LMWH, no anti-Xa activity-based guidelines have been issued till date.[ill date.–20 Antibill date.2without a substantial increase in mitral regurgitation.[If mitral stenosis is diagnosed before pregnancy, mitral commissurotomy is preferred. During pregnancy, the second trimester is the preferred period for any invasive procedure. Percutaneous valvuloplasty using the Inoue balloon technique has become the accepted treatment for patients with severe symptomatic mitral stenosis. Percutaneous balloon mitral valvuloplasty provides palliation for pregnant women with mitral stenosis, and the reported success rate is nearly 100%. Successful balloon valvuloplasty increases the valve area to >1.5 cmgitation. Althoughgitation. Valve regitation.The role of the anaesthesiologist begins by providing good labour analgesia. Most reports have recommended vaginal delivery under epidural anaesthesia, unless obstetrically contraindicated. Caesarean section is indicated for obstetric reasons only. In a study by Goldszmidt and others, only 29–27Combined spinal–epidural analgesia during labour using intrathecal fentanyl 25 μg produces good analgesia without major haemodynamic changes during the first stage of labour. During the second stage of labour, only the uterine contractile force should be allowed rather than the maternal expulsive effort that is always associated with the valsalva maneuver. Therefore, the second stage of delivery should be cut short by instrumentation. Supplementary analgesia for instrumentation with slow epidural boluses of fentanyl and a low concentration of bupivacaine reduces SVR and the cardiac pre-load. Low spinin situ could provide anaesthesia for immediate or post-partum tubal sterilization.Labour pain can affect multiple systems that determine the uteroplacental perfusion. Hence, foetal heart rate monitoring should be carried out during all stages of labour. Supplemental oxygen administration with pulse oximetry monitoring to minimize increases in pulmonary vascular resistance and maintenance of left uterine displacement for good venous return are mandatory. Supplementary epidural anaesthesia can be maintained throughout the immediate post-partum period and the catheter left The goals for the anaesthetic management of patients with mitral stenosis are: (1) maintenance of an acceptable slow heart rate, (2) immediate treatment of acute atrial fibrillation and reversion to sinus rhythm, (3) avoidance of aortocaval compression, (4) maintenance of adequate venous return, (5) maintenance of adequate SVR and (6) prevention of pain, hypoxaemia, hypercarbia and acidosis, which may increase pulmonary vascular resistance.There are no controlled studies examining the best type of anaesthetic technique in these patients and guidelines and standards are lacking. Therefore, individualizing the anaesthetic management according to the parturient’s cardiovascular status and the practitioners’ knowledge and experience of the existing treatment options is the key to success in these patients. For the One of the major advantages of epidural analgesia is that it can be administered in incremental doses and that the total dose could be titrated to the desired sensory level. This, coupled with the slower onset of anaesthesia, allows the maternal cardiovascular system to compensate for the occurrence of sympathetic blockade, resulting in a lower risk of hypotension and decreased uteroplacental perfusion. Moreover, the segmental blockade spares the lower extremity “muscle pump,” aiding in venous return, and also decreases the incidence of thromboembolic events. Invasive haemodynamic monitoring, judicious intravenous administration of crystalloid and administration of small bolus doses of phenylephrine maintain maternal haemodynamic stability.Continuous spinal anaesthesia, although infrequently practiced, could be a better option in some rare situations like accidental dural puncture. Dresner conducted 34 caesarean sections with cardiac disease under continuous spinal anaesthesia with a success rate of 99%. NeuraxiaGeneral anaesthesia has the disadvantage of increased pulmonary arterial pressure and tachycardia during laryngoscopy and tracheal intubation. Moreover, the adverse effects of positive-pressure ventilation on the venous return may ultimately lead to cardiac failure.Despite these disadvantages, if general anaesthesia is contemplated, tachycardia, inducing drugs like atropine, ketamine, pancuronium and meperidine, should be totally avoided. A beta-adrenergic receptor antagonist and an adequate dose of opioid like fentanyl should be administered before or during the induction of general anaesthesia. Because esmolol has a rapid onset and short duration of action, it is a better choice in controlling tachycardia. Since foetal bradycardia has been reported after esmolol, foetal heart rate should be monitored. Modified rapid sequence induction using etomidate, remifentanyl and succinylcholine is an ideal choice in tight stenosis with pulmonary hypertension.35 Mainte2α, produces severe hypertension, tachycardia and increased pulmonary vascular resistance.[After delivery of the foetus, oxytocin 10–20 u in 1,000 ml of crystalloid should be administered at a rate of 40–80 mu/min. An infusion of oxytocin can lower the SVR as well as elevate the pulmonary vascular resistance, resulting in a drop in cardiac output. Care must be taken during its administration. Methylergonovine, or 15-methylprostaglandin Fsistance.37Irrespective of the mode of delivery and anaesthetic technique, these patients are at a great risk of haemodynamic stress due to autotransfusion of blood from the uterus. This may lead on to pulmonary hypertension, pulmonary oedema and cardiac failure. Therefore, intensive monitoring and therapy should be continued till the haemodynamic parameters return to normal.Rheumatic mitral stenosis complicating pregnancy is still a frequent cause of maternal death. A better understanding of the physiological changes in pregnancy and the pathological impact of mitral stenosis over pregnancy and a multidisciplinary approach in diagnosis and management reduce the mortality and morbidity.


Myocardial motion is an important observable for the assessment of heart condition. Accurate estimates of ventricular (LV) wall motion are required for quantifying myocardial deformation and assessing local tissue function and viability. Harmonic Phase (HARP) analysis was developed for measuring regional LV motion using tagged magnetic resonance imaging (tMRI) data. With current computer-aided postprocessing tools including HARP analysis, large motions experienced by myocardial tissue are, however, often intractable to measure. This paper addresses this issue and provides a solution to make such measurements possible.To improve the estimation performance of large cardiac motions while analyzing tMRI data sets, we propose a two-step solution. The first step involves constructing a model to describe average systolic motion of the LV wall within a subject group. The second step involves time-reversal of the model applied as a spatial coordinate transformation to digitally relax the contracted LV wall in the experimental data of a single subject to the beginning of systole. Cardiac tMRI scans were performed on four healthy rats and used for developing the forward LV model. Algorithms were implemented for preprocessing the tMRI data, optimizing the model parameters and performing the HARP analysis. Slices from the midventricular level were then analyzed for all systolic phases.The time-reversal operation derived from the LV model accounted for the bulk portion of the myocardial motion, which was the average motion experienced within the overall subject population. In analyzing the individual tMRI data sets, removing this average with the time-reversal operation left small magnitude residual motion unique to the case. This remaining residual portion of the motion was estimated robustly using the HARP analysis.Utilizing a combination of the forward LV model and its time reversal improves the performance of motion estimation in evaluating the cardiac function. Cardiac dysfunction is associated with a variety of cardiovascular conditions that lead to heart failure. Significant cardiac events such as those in infarcted or diabetic hearts are associated with impaired relaxation and contraction of myocardium or abnormalities in left ventricular (LV) wall motion -5. TaggeTagged MRI employs electrocardiogram (ECG) gated acquisition. The imaging sequence contains initial saturation pulses followed by a repetitive image acquisition . At a spH and phase ϕ. The resulting complex signal H can be written as H = Hejϕ. While the magnitude is not of importance in motion quantification, the phase is considered to be the basis of the HARP analysis. The HARP is considered a material property of the moving cardiac tissue. Therefore, it can be used for tracking and quantifying the Lagrangian motion of myocardium.Quantification of the actual deformation in the LV wall involves accurately measuring the motion and relative displacements experienced by the myocardial tissue. For measuring the cardiac motion, HARP makes use of the information embedded in Fourier spectrum of the tMRI . The tag1 and H2 from which the distribution of  displacement is estimated from the phase differences between using the formulaHARP analysis requires two filtered complex image frames Hwhere ∠ denotes phase angle and * denotes comlex conjugate.Ii, i = 1 ... 5, depict the LV motion sequentially from end-diastole i = 1 to end-systole i = 5 in equally spaced time intervals. Under the circumstance of large motions, displacement measurements using HARP become a challenging task to perform. The computed phase difference (ϕ2-ϕ 1) in Eq. (1) wraps within the interval , as shown in Fig. I1 and I2 in Fig. During cardiac cycle, the LV wall experiences relatively large motions as seen in Fig. ference ϕ-ϕ 1 in EIn addition, statistical errors made during the estimation of large motions increase with the magnitude of the motion. Although, sophisticated signal processing approaches may improve the estimation performance by minimizing such errors, these methods also demand significantly increased computation time, as in the case of motion tracking algorithms employing window-based search techniques. In the presence of large motions, signal decorrelation between two image frames becomes a prominent factor in determining the errors. That is, a severe decorrelation between two windowed signals subsequently contributes to a motion estimation outcome with poor performance -15.T (Eq. B1). The operator involves a time-dependent parameter α accounting for the temporal changes in the LV size in the short-axis view at the mid-ventricle level. The function of the operator T can be thought of as radially contracting the image canvas I1 by an amount defined by α.It is possible to compensate for the degrading effects of signal decorrelation when the tissue motion is large. In our previous work in elastography imaging, we introduced global and adaptive regional signal stretching methods with the ultimate goal of producing better performance in displacement estimation . Signal T-1, i.e., the matrix-inverse of the forward motion operator T. Conceptually, the time-reversal operation can be considered as stretching the cardiac signals back in a radial fashion to the initiation of the systole. This effect is demonstrated in Fig. i on the average can be operated in reverse, but on an individual image from a given set of sequential images. The result is a time-reversed pseudo image where the LV wall shape and size are expected to be closely similar to those seen in the image in frame i = 1, which is acquired at the beginning of the systole. In cause and event terminology, the time-reversal operation attempts to reverse a displacement event, by inverting its cause, namely the systolic contraction.Mathematically, the time reversal of the systolic forward motion of the LV can be obtained by the inverse operator d of myocardial tissue at a spatial location in the LV wall can be decomposed into two components:The true displacement Δ denotes the bulk motion predicted by the time-reversal model. The term δ is the residual displacement that is not accounted for by the time-reversal operation and remains to be estimated between the image I1 and the time-reversed (TR) image. However, because the residual displacement is smaller in magnitude than the true displacement, its estimation results in small estimates with smaller errors when standard motion estimation algorithms are used.Here, To describe the above procedures in a compact form, we devise the following algorithm:T-1 to the desired image frame Ii with the corresponding αi.1. Obtain time-reversed image by applying Δ analytically from T-1.2. Calculate the amount of bulk motion δ between the time-reversed image TR = T-1 [Ii] and the first systolic frame I1 using a method of preference for the motion estimation, e.g., HARP.3. Estimate the amount of residual motion δ to Δ to get an estimate for the true total displacement d.4. Add Cardiac MRI data from the mid-ventricle level were collected from four male Sprague-Dawley rats. The rats were anesthetized using 1.5% isofluorane in a mixture of air and oxygen (60% and 40% respectively) and scanned using a 9.4 T horizontal bore scanner  and 60 mm radio frequency volume coil. ECG gated gradient echo based tagged images were captured from the short-axis view of the heart. The cardiac cycle was temporally resolved into ten equally incremented phases. The first five were the systolic frames. The following settings were used for the image acquisition: repetition time = 25 ms, echo time = 2.44 ms, number of averages = 1, field of view = 60 × 60 mm, image matrix = 256 × 256, slice thickness = 2.0 mm. The square grid tags had dimensions of width = 0.3 mm and separation = 0.8 mm. All experimental procedures were approved by the University of Kansas Medical Center Institutional Animal Care and Use Committee.T from the real tMRI data requires finding αi values such that the computationally-deformed end-diastole image I1 of the LV matches the image Ii in the sequence. The experimental data from each animal were preprocessed separately by following the algorithm described in Appendix A using all systolic frames. The resulting images were further processed to empirically find an optimal value for the deformation parameter αi for each systolic image frame Ii for i = 2 ... 5. This process involved superimposing a computer generated grid of binary grid mesh, on the LV image as described by the algorithm in Fig. T was applied to the undeformed mesh structure with a preselected αi0 value to deform the grid lines to match the tag lines in the image Ii as close as possible. The preselection was made based on the numerical simulations performed earlier. Next, an iterative optimization procedure was implemented to achieve a best match by varying the parameter αi. This procedure involved converting the LV image Ii to a binary form by applying an intensity threshold. The tag lines on the resulting image assumed zero intensity. Next, a logical XOR operation was performed between the binary image and the deformed grid mesh. The outcome of this operation in each position was 1 if the two pixel values were different, and 0 if they were the same. The results at pixels where the grid lines were collocated were summed. This sum was then normalized with the total number of pixels occupied by the lines on the grid mesh. A perfect match between the grid lines and the real tag lines would ideally produce a zero sum. This computational procedure was repeated for ten αi values distributed between a range divided in equal intervals; 0.9*αi0 <αij < 1.1*αi0, j = 1 ... 10. The value of αij producing the minimal normalized sum was selected as the optimal value for the deformation parameter αi for the frame i. When the normalized sum attained the same value for more than one αij, one of these values was selected by visually inspecting the matches on the computer screen.The characterization of the motion operator T-1 was applied on an image frame Ii with the corresponding optimal αi value. The resulting image TR was compared with the end-diastole image I1 and the HARP analysis was performed in between.The time-reversal operation This study was initiated to seek a simple, yet comprehensive model with a sufficient number of elements to accurately represent the LV wall motion at the mid-ventricle level. With a set of basic assumptions and simplifying approximations, we proposed the transformation in Eq. (B1) to model the myocardial motion during the systole. We specifically targeted the mid-ventricle for modeling the LV motion because this level experiences minimal amount of torsion and twisting during the heart beat, allowing the model to only account for the radial motion of the wall. We empirically constructed the model parameters using real tMRI data gathered from the hearts of four rats. This implementation involved data processing steps, which were described algorithmically in Appendix A. The initial step involved windowing and scaling the images to consistently depict the LV size and shape with the same dimensions at the end-diastole. This approach made the model versatile enough to analyze the LV motion in different species or minimize the inter-variation of the measurements when the same species is considered. This feature of the model increases its capacity by simulating the LV motion in both humans and animals.α for quantifying the temporal motion in the systolic phase of the cardiac cycle with sufficient accuracy. Requiring only one parameter to reasonably describe the myocardial deformation is another important feature of this model. Table α from the tMRI data obtained during the studies. The data in the table are also plotted against the frame numbers in Fig. α increases with time in a nonlinear fashion to accommodate the shrinkage of the LV size during the systolic contraction. Figure α values at different time points, establishes a normative database which may be used as reference for the comparison of results from tMRI experiments preformed on rats with abnormal cardiac conditions.Irrespective of whether the data is clinical or experimental, our LV model requires estimating a single deformation parameter α is a good area for future exploration in cardiac imaging research. Such a relation could, in principle, indicate a certain systolic dysfunction associated with certain diseases or abnormalities, such as diabetes. Similarly, another useful parameter well accepted by clinicians is the myocardial strain rate. By calculating the differences in strains exhibited by the LV tissues from one systolic phase to another, more insights may be gained regarding the myocardial behavior and its time dependence. These and other potential merits of the proposed motion model of the LV are left for future work.Our model is also open to other clinical relevance. For example, strain calculation and its relation to the parameter α values in Table α in time, one can reconstruct simulated pseudo images corresponding to a specific time point chosen within the systolic phase of the cardiac cycle. These computational processes can be carried out offline by applying the transformation T to the canvas of the end-diastole image frame i = 1 with the desired α value. Sample results from such computations are shown in Fig. From another aspect, knowledge of the A literature search reveals numerous approaches that have been employed to model the LV wall motion ,17. ExamDespite its ability to describe the myocardial forward motion, our model suffers from two main limitations. The first limitation is that the model treats the entire myocardium as if it were contracting homogeneously. While such treatment greatly simplifies the problem, it ignores the heterogeneous nature of myocardial contractility. Evidently, contractility varies with the position of the myocardium such that tissues in the wall exhibit deformation profiles that differ from those of the septum. This variation in deformation is due to the fact that, depending on the location, some tissues have constraints that limit their motion while others do not. Accommodating this behavior with regional dependencies requires more complicated models to better describe the myocardial motion.Another limitation of the model is its inability to handle twisting (torsion) motion that takes place in the basal and apical levels of the LV wall. Thus, the model is limited to work at the mid-ventricle level where the twist is minimal. Nonetheless, adding a twisting ability is plausible and computationally possible by having position-dependent angles to account for rotation in the transform operator in Eq. (B1). Such integrations are likely to increase the capability of the model to represent the myocardial motion at various levels of the LV in short axis views.Although a typical cardiac cycle is composed of both systolic and diastolic phases, we chose to focus the model on systolic motion only. This approach was chosen to simplify the problem, knowing that we could easily extrapolate the analysis to include the diastolic motion if desired.I1 and I2 using HARP analysis. The large motion between the frames is clearly seen to produce phase wraps. Figure I1 ] of the frame i = 2  pair than it is in the  pair, making the former pair favorable for the motion calculations once the noise is taken into consideration.Figure  I1 Fig.  and I2  by inverting its cause (systolic contraction) is seen as playing a beneficial role in improving the performance of the motion estimation with HARP. The bulk motion component Δ in Eq. 2 represents the average behavior of the subject population, and analytically available from T-1, for a given α value in Table Δ is primarily responsible for the resulting phase wraps, observed in Fig. Δ and I1,I2).Figure Δ = , , , ,  and . This example and quantitative measurements clearly demonstrate the advantage of our approach. Preprocessing systolic frames with the time reversal operation prior to performing HARP analysis improves the performance of cardiac motion estimates from tMRI.Figure The simple prior time-reversal operation applied to a systolic image with the forward model of the LV wall motion accounts for the large displacements experienced by the myocardial tissue in sequentially-acquired tMRI data. The remaining smaller magnitude regional myocardial motions in the time-reversed image can be computed by an estimation technique selected by the user. Using this two-step approach, we showed that HARP analysis became more immune to phase wrapping and consequently the motion estimation performance is enhanced. Robust measurements obtained with our approach therefore allow better interpretation of the cardiac motion. This should enable computation of accurate strain fields to characterize the regional deformation aimed at evaluating the function, viability and pathological state of the underlying myocardial tissue.TA helped with data acquisition and performed numerical simulations and computations. IVS participated in the design and coordination of the study. LTC participated in modeling the LV wall motion. MB conceived of the study, participated in its design and coordination, interpreted the results and drafted the manuscript. All authors read and approved the final manuscript.C of the LV. The average of the lengths of the two lines was used as a measure of the LV diameter D. Next, a square window with equal size D in each dimension and centered at C was drawn to distinctly enclose the LV wall. A second concentric square window was applied with a slightly larger dimension N = 1.3*D to extract a broader region containing the LV wall of the heart and the surrounding tissue mass. This last window was also used to segment out the LV from the remaining systolic image frames Fi for i = 2,3 ... 5. Finally, the extracted images from all frames were interpolated to an increased dimension of 256 × 256 pixels to obtain the final systolic image set Ii for i = 1,2 ... 5. With this standardization outlined and depicted in Fig. A set of image processing routines was implemented for application on the tMRI data prior to performing the motion analysis. The main task of these routines was to ensure that the resulting model was generic enough to either represent the myocardial motion in different species or account for the variations seen in the heart volumes within the same species under normal or pathological conditions. Application of this procedure aimed to segment out a portion of the acquired tagged image to visualize the LV in a larger short-axis view at the mid-ventricle. This segmentation process is given in detail in Fig. Current research efforts are focused on spatio-temporal modeling of the LV shape and motion. To aid these efforts and provide a model for the time-reversal operation in the main body of the paper, here, we introduce a mathematical construct as a means of quantitatively describing the LV wall motion in a beating heart.For clinical analysis or evaluation purposes, the short axis view of the heart is divided into three sections, namely base, mid-ventricle and apex. This division is in accordance with the standardized myocardial segmentation published by the American Heart Association . To perfBefore proceeding further, we make the following basic assumptions for constructing the model to properly represent the LV motion at the mid-ventricle.1) The myocardial tissue deforms the same manner whether it is in the septum or outer LV wall.Fi for i = 1,2 ... 5, where i = 1 is the end diastole frame and i = 5 is the end systole frame.2) Although a full cardiac cycle includes both systolic and diastolic phases, to keep the analysis simple, the model is built to mimic the systolic LV motion only. Nonetheless, it is straightforward to extrapolate the analysis to include the diastolic phase if desired. The digital cardiac images acquired sequentially in equally spaced time intervals in the systolic phases are identified by the frames 3) The cardiac images are constructed on a virtual canvas with rubber sheet properties that can be digitally stretched according to a spatially varying deformation pattern. With this elastic feature, the canvas serves as a basis upon which the model acts through the application of a spatial perturbation in the coordinates of the myocardial tissue. Thus, such a spatial transformation describes the local myocardial motion. As shown below, the canvas' elastic behavior is exploited through the use of time-forward operations applied on the images to simulate the real myocardial motion.T defined byThe mathematical basis for modeling the LV motion in the current work has been described in . The modx and y represent spatial coordinates. The parameter α in the exponent is responsible for the amount of radial deformation applied on the canvas, and is therefore time dependent when the serially-acquired image frames are considered. The real cardiac tMRI data are used to estimate αi in characterizing the LV motion from the first frame i = 1 (α → 0) to a selected frame Ii, i = 2,3,4 or 5, in Fig. I1 in Fig. T [I1] yields the deformed image I2 in Fig. α; small α yields small wall motion and large α produces large wall motion.Here α alone can be seen as capable of mimicking the changes in the LV wall's diameter and thickness.To accurately describe the myocardial motion, it is necessary to satisfy two main criteria observed in the MR experimental data, as discussed in the literature. First, the transformation function should exhibit radial dependence, so that image coordinates closer to the LV cavity's center are deformed more than those further away from the origin. This criterion is clearly satisfied in Figs.


Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiomyopathy. The identification of patients with HCM is sometimes still a challenge. Moreover, the pathophysiology of the disease is complex because of left ventricular hyper-contractile state, diastolic dysfunction, ischemia and obstruction which can be coexistent in the same patient. In this review, we discuss the current and emerging echocardiographic methodology that can help physicians in the correct diagnostic and pathophysiological assessment of patients with HCM. Hypertrophic cardiomyopathy (HCM) is clinically defined in presence of left ventricular (LV) hypertrophy in the absence of hypertension and valve disease. LV hypertrophy without cardiovascular causes occurs in approximately 1:500 of the general population . This inHCM may be initially suspected because of an heart murmur, positive family history, new symptoms or abnormal ECG pattern showing LV hypertrophy and abnormal Q waves. Thereafter an echocardiogram is usually performed.The first echocardiographic diagnostic criteria in HCM were established by using M-mode imaging which included asymmetrical septal hypertrophy, systolic anterior motion of the mitral valve (SAM), a small LV cavity, septal immobility, and premature closure of the aortic valve -3. LV thThe movement of mitral valve is easily visualized by M-Mode and its anterior motion during systole, together with asymmetrical septal hypertrophy, was initially thought to be pathognomonic of HCM. However, these findings may be present in other forms of secondary and primary hypertrophy, like chronic systemic and reno-vascular hypertension , Fabry'sLeft atrial (LA) diameter is usually increased in patients with HCM because of obstruction and/or diastolic dysfunction. LA diameter gives informations about the risk of atrial fibrillation, of heart failure development and of cardiac mortality  which isThis technique by visualizing the whole heart has come the recognition that LV hypertrophy is most often asymmetrical and it can be confined in specific LV segments such as the apex.Currently, using short-axis view the left ventricle is divided in 4 LV wall segments: anterior and posterior septum and posterior and lateral wall Figure . In almoThe heterogeneous distribution of hypertrophy in HCM results in a distortion of internal LV shape allowing algorithms, generally used to measure LV mass, not applicable in this disease. As a consequence, several echocardiographic indexes have been developed to measure the distribution and the extent of LV hypertrophy. Wigle et al  proposedThe degree of LV hypertrophy varies throughout life. In fact, although the gross phenotypic expression and clinical profile of HCM may occasionally be identified in infants and young children, marked LV hypertrophy is rarely documented during the first years of life . ConversGenetic studies among large families demonstrated that morphological LV hypertrophy reaches a plateau at the third decade of life in β-myosin heavy chain and in α-tropomyosin mutations, whereas it increases continuously thought life in cardiac myosin binding protein C mutations . The cliAlthough LV remodeling in children is characterized by progression of hypertrophy, the changes in cardiac morphology observed in some adults with HCM occur in the context of development of systolic dysfunction (defined as LV ejection fraction <50%) associated or not to LV wall thinning  Figure . This unCross-sectional echocardiographic analyses of large HCM patient populations encompassing a broad age spectrum ,29 have At opposite site, there is evidence of high degree of hypertrophy suggestive of HCM in elderly patients with and without history of arterial hypertension ,31. In tFinally, among the spectrum of sarcomeric contractile protein disease, idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations .Echocardiography can visualize thickened LV walls with high sensibility and specificity, however it cannot distinguish conditions based on myocyte hypertrophy from those in which LV mass and wall thickness are increased by interstitial infiltration or intracellular accumulation of metabolic substrates. Cardiac magnetic resonance (MRI) may help into diagnostic iter (see below), moreover the final diagnosis is given only in some specific conditions by myocardial biopsy, and in particular is not indicated for the final diagnosis of HCM ,35. On tIn the contest of genetic disease, thickening of LV walls can results also by mutations in non sarcomeric proteins involving or the gene encoding the γ-2-regulatory subunit of the AMP-activated protein kinase (PRKAG2), or the gene encoding lysosome-associated membrane protein 2 (LAMP-2), resulting in Danon-type storage disease with clinical manifestations limited largely to the heart   Figure . OverallAnderson-Fabry disease is a relatively frequent cause of idiopathic LV hypertrophy. It is a X-linked lysosomal storage disorder caused by α-galactosidase mutations and it is characterized clinically by widespread variety of signs and symptoms. Cardiac findings include LV hypertrophy, showing a symmetrical pattern in the majority of cases, mild diastolic dysfunction and preserved LV ejection fraction as well as no LV outflow tract obstruction (LVOTG) Figure . The useMitochondrial disorders result from abnormalities in mitochondrial DNA and function; mitochondrial DNA is inherited maternally, and most of these disorders are transmitted from mother to children of both sexes. In some mitochondrial disorders, LV concentric hypertrophy is present as well dilated cardiomyopathy, which probably represents a progression from the hypertrophic form. In most patients, conduction abnormalities are present  Figure .Involvement of the heart is a common finding and is the most frequent cause of death in amyloidosis; cardiac amyloidosis occurs more commonly in men than in women, and it is rare before the age of 40 years. The onset of clinical cardiac disease usually occurs late in life. Echocardiography is characterized in the majority of cases by symmetric LV hypertrophy, dilated atria and pericardial effusion Figure . In someOne of the most discussed issue is how to role out HCM in athletes. Diagnosis of HCM in athletes is important, given the high propensity to sudden cardiac death in HCM patients engaging in competitive sports as well as other physically intense activity . AlthougIn Figure Right ventricular hypertrophy is diagnosed when two or more right ventricular segments are hypertrophied and when at least two right ventricular wall measurements exceed two standard deviations from the mean recorded in normal subjects. Using these criterions McKenna et al  reportedAlthough SAM is the most frequent mechanism of LVOTG, obstruction can occur at mid-ventricular level or at multiple levels in the same patient and is variable with time. Continuous Doppler will give informations about the degree of obstruction (see later) whereas by pulse wave Doppler LV mapping will be performed to determine the site of obstruction. Mid-ventricular obstruction has been diagnosed by the typical angiographic feature of hourglass appearance of the left ventricle with mid-ventricular obliteration and apical chamber that is variable in size and contractility. Echocardiography has the same potential to identify this haemodynamic type of HCM Figure . PatientLA volume measured by two-dimensional echocardiography has some clinical and prognostic implications. LA remodeling, measured by LA volume, relates directly with exercise tolerance as demonstrated by Sachdev et al  in patieEach Doppler technique offers relevant contribution in the analysis of patients with HCM .Evaluation of the presence and degree of mitral regurgitation is performed by color Doppler echocardiography. Mitral regurgitation occurs in almost all patients with obstructive HCM as a consequence of SAM which induces abnormal mitral leaflet coaptation and may be an important cause of dyspnea. When additional mitral valve abnormalities other than SAM are not observed, a direct relation between the pressure gradient and the severity of MR is evident . The dirApproximately 25% of patients with HCM have a significant resting pressure gradient, i.e. ≥30 mmHg, between the body and LV outflow tract. This is nearly always accompanied by SAM. Continuous wave Doppler is used to determine peak LVOTG with caution exercised to exclude the mitral regurgitation jet  Figure . This laIt is well recognized that some patients without outflow obstruction at rest have gradients that can be provoked by physiological and pharmacological interventions that diminish LV end-diastolic volume or augment LV contractility. The term labile obstruction has been used to describe the spontaneous appearance and disappearance of obstruction and latent obstruction to describe gradients that only appear with provocation. A number of methods can provoke obstruction in the echocardiography laboratory, including Valsalva maneuver, amyl nitrite, and dobutamine. However, these methods are not standardized and can underestimate the degree of obstruction such as Valsalva maneuver or have low specificity such as dobutamine. Exercise is a physiologic means of provoking latent LVOTG. Over 50% of HCM patients without significant outflow tract obstruction at rest will demonstrate outflow gradients over 30 mmHg with exercise ,54. AlthRight ventricular outflow tract obstruction may coexist with LVOTG in a minority of patients with massive septal hypertrophy and occasionally it is isolated .Figure Pulsed Doppler at mitral and pulmonary level is used to assess the presence and the degree of diastolic dysfunction. Almost all patients with HCM have some degree of LV diastolic dysfunction. Figure New technologies have been employed in the patho-physiological assessment, in preclinical diagnosis, in differential diagnosis, and in risk stratification of HCM.Contrast echocardiography currently is used to enhance endocardial definition, Doppler signals, and to evaluate myocardial perfusion during percutaneous transluminal septal myocardial ablation (PTSMA). PTSMA is a catheter interventional treatment which involves the introduction of absolute alcohol into a septal perforator branch of the left anterior descending coronary artery to produce a myocardial infarction within the proximal ventricular septum. The aim is similar to that of myotomy-myectomy, i.e. reducing the basal septal thickness and excursion enlarging the LV outflow tract and, thereby, lessening the SAM of the mitral valve and mitral regurgitation. The introduction of the echo contrast has proved to reduced the side effects of the technique: it selects the appropriate septal perforator branch determining the precise area of septum targeted for alcohol ablation and evaluates whether selected septal perforator also perfuses other distant and unwanted areas of LV or right ventricular myocardium or papillary muscles .A potential role for contrast enhancement in the diagnosis of apical HCM has been demonstrated , althougGiven the complex interplay of factors causing diastolic dysfunction in HCM, it should not be surprising that no single non-invasive measure has been definitively validated. Nagueh et al  suggeste++ sensitivity [TDI has been investigated in the preclinical diagnosis of HCM. Studies from transgenic animal models revealed some abnormal myocardial function at a time preceding the development of LV hypertrophy, firstly due to alterations in Casitivity  which prsitivity ,67, addiPatients with HCM may show regional differences in wall motion at rest . BetocchIn the last decade several papers have been published using strain rate technique, either TDI and speckle , to investigate regional systolic function. Ganame et al  demonstrStrain rate imaging has been shown to measure accurately LV torsion . LV untwA frequent clinical issue is to establish the final diagnosis in patients with high degree of LV hypertrophy and arterial hypertension; recently, more severely reduced systolic compression (by strain Doppler echocardiography) along with asymmetric LV hypertrophy readily identified HCM patients from those with hypertension . ReceiveStrain rate imaging has been involved in the differentiation of HCM from cardiac amyloidosis in one study where, however, patients with amyloidosis were in the late stage characterized by low ejection fraction. This suggests that the early differentiation of amyloidosis versus HCM using strain  may be still difficult .Real time 3-dimensional echocardiography has been applied to determine LV mass, but there is a paucity of data about its accuracy in HCM. To date, MWT remains the best and the more simple and important measurement that should be reported, because it can predict sudden cardiac death in this population.Stress echocardiography with dypiridamole has been used to test prognostic role of electrographic signs of inducible ischemia in patients with HCM. In one paper , ECG sigQuantitative evaluation of coronary flow reserve studied by positron emission tomography is a strong predictor of progression to severe symptoms and to ES HCM . An estiMRI is an important imaging technique with an expanding role in the contemporary evaluation of patients with HCM; it provides complete LV reconstruction and a precise definition of the distribution and pattern of hypertrophy . This isIn patients highly suspected to have HCM, but with a negative echocardiogram for LV hypertrophy, MRI represents an additive diagnostic chance as proposed by Rickers et al; Authors found, in a population involving almost 50 patients, that MRI was capable of identifying regions of LV hypertrophy  not readily recognized by echocardiography, which were solely responsible for diagnosis of the HCM phenotype in an important minority of patients . MoreoveThe diagnosis of HCM is most easily and reliably established by clinical and instrumental examination in the majority of affected adult patients. Thus, in patients with certain clinical diagnosis, genetic testing represents only a diagnostic confirmation. Nevertheless, molecular studies have the potential to enhance diagnostic reliability in HCM and can play an important role in resolving ambiguous diagnoses . MoreoveTwo-dimensional echocardiography has been the most used, efficient and accessible technique for establishment of the diagnosis of HCM. Echocardiography can provide important information for the appropriate diagnosis and pathophysiological assessment of HCM patients. However, echocardiography alone can not differentiate different forms of unexplained LV hypertrophy. It must be underscore that its role is highlight only when is used after a complex clinical evaluation including familial and personal anamnesis, clinical examination, electrocardiogram, haemato-chemical tests.The authors declare that they have no competing interests.MAL conceived the review and drafted the manuscript. SN e MG suggested the scheme of the review and revised critically the paper. SB revised critically the manuscript and added figures which resulted in a more readable manuscript. FC and IO revised critically the manuscript and gave important changes before the final submission. EA and PB performed a statistical analysis when necessary and revised critically part of the bibliography giving important criticism on the prognostic role of echo in patients with HCM. SB and ADA helped in the collection of the bibliography suggesting some important papers reported in the review and improved the chapters concerning the differential diagnosis in patients with HCM. ADE and DM contributed and improved the chapters concerning the role of new technologies. SS participated in the design of the review. SM participated in the design of the review and gave the final approval. All authors read and approved the final manuscript.