Diagnosis of cardiomyopathies : tips and tricks for internists and general practitioners

Cardiomyopathies are little known to internists and general practitioners (GPs), and not always able to arouse the interest of cardiologists. Probably, this happens because cardiomyopathies are perceived as rare and complex disorders, a prerogative of a few dedicated centers. This may partly explain why the diagnosis of cardiomyopathy is often missed and, consequently, why cardiomyopathies are largely underdiagnosed. Internists and general practitioners should have an interest in these conditions, because cardiomyopathies are not as rare as generally perceived, and because their complexity can be unravelled with knowledge and methodology. Cardiomyopathies are defined as myocardial disorders in which the heart is structurally and functionally abnormal in the absence of coronary artery disease or abnormal loading conditions. Irrespective of the cardiac imaging technique used, a limited number of phenotypes are defined based on ventricular morphology and function. These basic phenotypes include hypertrophic, dilated, restrictive and right ventricular arrhythmogenic cardiomyopathies. Aim of this review is to describe a simplified approach to the detection of the underlying causes of specific phenotypes. We will focus our attention on the basic phenotypes, presenting a diagnostic work-up and a suggestive clinical case for each phenotype.


Introduction
Cardiomyopathies are little known to internists and general practitioners (GPs), and not always able to arouse the interest of cardiologists themselves.Probably, this happens because they are perceived as rare and complex disorders, a prerogative of highly specialised centres.This may partly explain why their diagnosis is often missed and, consequently, why they are considered largely underdiagnosed.
Cardiomyopathies are defined as myocardial disorders in which the heart is structurally and functionally abnormal in absence of coronary artery disease (CAD) or abnormal loading conditions. 1 Irrespective of the cardiac imaging technique used, a limited number of phenotypes are defined based on ventricular morphology and function. 2These basic phenotypes include hypertrophic (HCM), dilated (DCM), restrictive (RCM) and right ventricular (RVC) cardiomyopathies.The diagnostic work-up starts at this point and the main challenge is shifting from a descriptive level to an aetiological one. 3im of this article is to describe a simplified approach that may help the non-specialist in the detection of the underlying causes of specific phenotypes, or at least may arise the diagnostic suspicion of cardiomyopathies in their everyday practice, referencing consequently the patients to specialised centres.We will focus our attention on the basic phenotypes, presenting a diagnostic work-up and a clinical case example for each of them.
The overall prevalence of all cardiomyopathies is estimated at least 3% in the general population. 4Nonetheless, some entities of this broad spectrum are largely underdiagnosed.Indeed, the new estimated prevalence of HCM is about 1:200 5 and, thus, the chance of meeting an affected patient in the everyday practice is higher than commonly thought.
The chance of diagnosing a cardiomyopathy increase if the clinician has acquired a so-called cardiomyopathy-specific mindset: 3 the attitude to interpret the clinical, laboratory and instrumental findings in the context of a phenotypically defined cardiomyopathy.
The diagnostic pathway stars with a basic diagnostic approach that relies on simple tools, easily performable in any clinic: family history, physical examination, electrocardiogram and echocardiogram.This phase is crucial: the presence of clinically and instrumentally derived findings, commonly known as diagnostic red flags, may suggest a specific cause for a defined phenotype or may restrict our attention to a narrower spectrum of conditions.The approach to all patients should be multidisciplinary in nature, and the following steps of the work-up need a stepwise selection of appropriate diagnostic techniques. 3It also represents an iterative process in which the findings are acquired and the case constantly revalued in light of new information in order to identify a specific cause or let other differential diagnosis emerges.

Hypertrophic phenotype
The HCM is defined by the presence of increased left ventricular wall thickness that is not solely explained by abnormal loading conditions. 6It represents the most common cardiomyopathy and its diagnosis is based on quantitative criteria, derived by the morphological evaluation of the left ventricle by cardiovascular imaging techniques, primarily the echocardiogram. 7][10] In about a quarter of cases the aetiology remains unknown.
The basic approach helps to exclude the most common causes of left ventricular hypertrophy (LVH) due to abnormal loading conditions (longstanding hypertension, valve diseases, congenital disorders, athlete's heart) and, at the same time, allows collecting features suggestive of a specific cause. 11Other diagnostic clues can be collected with further specialised tests and multidisciplinary consultations.If this diagnostic process does not bring to a specific diagnosis, genetic test is than recommended. 12If a specific cause does not emerge even after genetic testing, all diagnostic clues should be reassessed, new and different diagnostic techniques considered and a multidisciplinary team meeting organized. 13espite all efforts, in the 25% of cases it is not possible to recognize a definitive cause of HCM.
The family history can be useful in distinguishing between genetic and non-genetic causes. 14 unexplained heart failure, pacemaker/defibrillator implantation, cardiac transplantation and other organ system involvement, all suggest a possible genetic cause.The pedigree analysis helps us to recognize the pattern of inheritance.Most of the genetic forms of HCM display autosomal dominant inheritance. 15,16On the other hand, autosomal recessive inheritance is less common and is typical in Friedreich ataxia and some mitochondriopathies. 17 The X-linked inheritance is the typical pattern of uncommon conditions such as Fabry and Danon disease. 18The matrilineal patter of inheritance is a specific clue of mitochondriopathies caused by mitochondrial DNA mutation. 19he age is a potential diagnostic clue: the presence of HCM in neonates and children suggests a congenital syndrome or an inherited metabolic disorder; 20 genetic forms due to sarcomeric gene mutations are most common in young adults but can occur in any age of life; 6 Danon disease occurs commonly in the first decades of life, 21 while senile amyloidosis occurs primarily in the elderly. 22The symptoms in patients with HCM are non-specific and the physical examination is nearly normal in patients without an obstructive.In these last some typical features are present: a rapid upstroke and downstroke to the arterial pulse; an ejection systolic murmur due to LVOT obstruction (LVOTO) or to systolic anterior movement of the mitral valve (SAM). 23ther non-cardiovascular signs and symptoms that may suggest a specific cause of HCM are (Table 1): dysmorphorphic face in genetic syndrome such as Danon disease; 3,21,24-27 visual impairment in mitochondriopathies; 3,28 palpebral ptosis in mitochondriopathies and myotonic dystrophy; 3,28 sensorineural deafness in mitochondriopathies and Fabry disease; 3,28,29 angiokeratomata in Fabry; 3,29 sensory abnormality and bilateral carpal tunnel syndrome in amyloidosis. 3he electrocardiogram is typically abnormal in patients with HCM and is often the earliest manifestation, warranting further diagnostic evaluation and having a prognostic role. 30,31Some ECG patterns in presence of LVH may suggest a specific cause of HCM (Table 1): giant T-wave inversion on inferolateral leads in apical HCM; 32 low voltage pattern with pseudoinfarct pattern in forms of amyloidosis other than TTR-amyloidosis; 33,34 extreme high voltage pattern in storage diseases such as Danon and Pompe disease; 35 short PR, with pre-excitation in many storage and mitochondrial diseases 36,37 or alone in Fabry disease. 38][44] The first-level laboratory tests performed in HCM are listed in Table 1 and may contribute to the diagnosis.
Other diagnostic tools, such as cardiac magnetic resonance (CMR), nuclear scintigraphy, genetic testing and endomyocardial biopsy, remain useful in diagnosis clarification and prognostic assessment, but for their costs, diffusion and invasiveness are still considered as second level techniques, their adoption in Internal Medicine Departments still being very limited.

First clinical scenario
A 74-year old woman was admitted in our hospital because of recurrent episodes of chest pain.She had previously been admitted at the local Cardiology Department for the same reason, when a coronary angiogram showed normal epicardial coronaries.
The basic approach evidenced: a personal history diabetes mellitus and hypercholesterolemia, without hypertension, and a family history of CAD; an unremarkable physical examination; mild kidney failure on laboratory tests; inverted T-waves in Lead I, aVL and from V 3 to V 6 leads on ECG (Figure 1A).The echocardiogram was technically challenging because of obesity.Anyway, showed normal LV size cavity with concentric hypertrophy, an isoechoic apical formation with concomitant wall motion abnormality, and low-normal systolic function (Figure 1B).
The presence of an apical mass with concomitant wall motion abnormalities prompted the following differential diagnosis: apical thrombus, apical tumour, isolated LVNC, atypical presentation of HCM and apical obliteration due to endomyocardial fibrosis. 45,46he unremarkable recent coronary angiogram performed seemed to exclude a CAD.To better characterize the apical region a CMR was proposed but declined by the patient because of claustrophobia.Contrast echocardiogram was than performed using lung-penetrating agent 47 and revealed hypertrophy of the apex with maximum apical wall thickness of 17 mm (Figure 1C).The ECG pattern was than the only red flag: the presence of giant T waves inversion in precordial and lateral leads, as described above, is indeed typical in apical forms of HCM.
Genetic testing was performed and revealed MYBPC3 gene mutation.
We concluded for apical hypertrophic cardiomyopathy due to sarcomere gene mutation with severe recurrent episodes of chest pain, which responded to beta-blocker.

Dilated phenotype
In DCM we should deal with a much complex phenotype, also at descriptive level. 48The most common causes of LV dilatation and dysfunction are CAD and abnormal loading conditions (longstanding hypertension, valve diseases, congenital disorders). 49When these are excluded, usually with a coronary angiogram and a cardiovascular imaging technique, less common causes should be considered.The information obtained by the basic approach can guide the physician in distinguishing between genetic and non-genetic causes (myocarditis, toxic damage from heavy metals, infiltrative disorders and metabolic derangements), and in planning subsequent work-up. 3bout the history taking, the most common questions concern the duration of disease, the rate of progression, the presence of antecedent illness, a history of recent travels, the presence of abnormal loading conditions, the use of drugs, alcohol or the exposition to other toxins and the presence of coronary risk factors. 50In order to understand if we are dealing with a genetic cause, a family tree should be drawn and a pedigree analysis performed.Nonetheless, a not significant genetic tree does not exclude a genetic cause of DCM because of the low penetrance of many genetic mutations. 51 history of premature atrial fibrillation, conduction diseases, pacemaker and/or defibrillator implantation suggests the presence of genetic causes such as laminopathies, desminopathies and some dystrophinopathies. 52,53In this case the pattern of inheritance could be helpful. 54Many genetic causes have also manifestations in other organ systems: for example, a familial history of neuromuscular disease and a personal history of diabetes and sensorineural deafness could suggest mitochondriopathies. 17 If genetic causes are unlikely or have been without success by performing genetic tests, other non-genetic disorders should be considered.Myocarditis is the most common cause among them and could be related or non-related to infections. 55 recent history of unknown fever and travels in foreign countries could suggest an infective myocarditis, while a personal history of autoimmune diseases or signs and symptoms of systemic inflammatory disorders can suggest a non-infective myocardi- tis.Some symptoms and signs may suggest a specific cause of DCM (Table 2): the presence of intellectual disability may suggest a mitochondrial cause 17 and dystrophinopathies; 56 sensorineural deafness in mitochondriopathies; 17 gait disturbance and muscle weakness in neuromuscular diseases; 57 pigmentation of skin and scars is a specific sign of hemochromatosis. 58he ECG in DCM shows usually less clues than other cardiomyopathies (Table 2). 52An acute AV block presentation may suggest myocarditis, while a chronic stable form suggests cardiac sarcoidosis or genetic causes (laminopathies, desminopathies, myotonic dystrophy).A premature paroxysmal AF may be a manifestation of SCN5A mutation, 59 laminopathies 53 or polygenic disorder.
The echocardiogram in DCM does not give many red flags (Table 2): a phenotype that meet the diagnostic criteria for left ventricular non-compaction (LVNC), does arise the suspicion of a genetic form of DCM; a mild dilatation, in presence of akynetic segments with non-coronary distribution, may be present in myocarditis and cardiac sarcoidosis; a dilated LV with posterolateral akynesis, in absence of CAD, suggests a dystrophin-related cardiomyopathy. 3,48,49,60ome laboratory tests may help in differential diagnosis of genetic and nongenetic causes of DCM (Table 2). 3,48,49,60sually the diagnostic pathway is completed, at least, by the execution of a cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and 48-h ECG Holter monitoring.The CMR may show: a dilated LV with global hypokinesis, reduced ejection fraction and non-coronary LGE distribution in non-ischaemic cardiomyopathies; 61,62 the presence of extensive oedema on T2 mapping is a red flag for inflammatory myocarditis; 63 the akynesis of basal septum with presence of LGE suggests a cardiac sarcoidosis; 64 a short T 2 * may suggest a myocardial iron overload for its highly sensibility in detecting myocardial iron deposition. 65The 24-h ECG monitoring may show the presence of some arrhythmias potentially responsible for forms of reversible LV dysfunction known as tachycardia-induced cardiomyopathies. 66ardiac scintigraphy 67,68 and/or endomyocardial biopsy (EMB) 69,70 are sometimes necessary to achieve the diagnosis.A positive cardiac 18F-FDG-PET scan, in the suspicion of an inflammatory cardiac involvement, can reinforce the hypothesis of inflammatory-induced myocarditis.

Second clinical scenario
A 53-year old woman was admitted to our Department due to the sudden onset of shortness of breath on minimal exertion and palpitations.
She had no family history for cardiovascular disorders, and reported a personal history of autoimmune disorders such as Hashimoto's thyroiditis, vitiligo and psoriasic arthritis.The careful physical examination showed only mild ankle swelling.The Review  A coronary cause was excluded performing a coronary angiogram, which was unremarkable.Other possible causes were excluded performing a CMR (Figure 2B) that showed mild and patchy areas of myocardial oedema on T2-waighted imaging and non-coronary distribution of LGE in midwall.In absence of other clinical findings suggesting a specific cause, our diagnostic suspicion was oriented towards a non-genetic cardiomyopathy: the personal history of autoimmune disorders, the sudden onset of symptoms and the increase of inflammatory markers all suggested an inflammatory cardiomyopathy.Furthermore, the LGE pattern prompted to consider a differential diagnosis between myocarditis and cardiac sarcoidosis.

Review
The 18F-FDG-PET scan, performed to evaluate a possible cardiac inflammation, showed a mild and diffuse LV enhancement (Figure 2C).The EMB was performed but was non-conclusive.In this case we concluded for a probable inflammation-induced cardiomyopathy, in a patient with a significant history of autoimmunity.The case was than discussed in a multidisciplinary team meeting and, based on the severity of symptoms, despite a non-severely reduced systolic function, an immunosuppressive therapy, based on prednisone and methotrexate both 1 mg/kg/daily, was than started.Therefore, a 90-day follow-up, based on clinical status, echocardiography, 18F-FDG-PET scan and cardiac and inflammatory biomarkers, was planned.

Restrictive phenotype
Restrictive cardiomyopathy is defined as restrictive ventricular physiology in presence normal or reduced systolic and diastolic volumes of one or both ventricles, and normal ventricular wall thickness. 1It represents the most difficult phenotype to approach in the field of cardiomyopathy because it is physiology-based, because the restrictive pattern of ventricular filling (rapid raise in ventricular pressures in presence of small increase in volume) due to the myocardial stiffness shows itself only in the late phases of the disease, and the boundary between the hypertrophic and the restrictive phenotype is somehow vague. 71,72he causes of RCM can be classified in genetic and acquired.RCM can be grouped, based on causative classification, in four main categories: interstitial fibrosis (idiopathic RCM, 73,74 sarcomeric RCM, 75 78 hypereosinophilia syndrome, 79 drugs, 80 etc.).
Thus, when the suspicion of RCM arises from a preliminary evaluation, some red flags could help us in identifying a specific cause.
About signs and symptoms, few specific clues should be considered (Table 1): the intellectual disability may suggest the Noonan syndrome; 26 sensory abnormality, paraesthesia and/or carpal tunnel syndrome, are common in amyloidosis, especially in AL form; 81 a history of muscle weakness is typical in desminopathies. 82he ECG (Table 1) may show AV block in especially in amyloidosis and in desminopathies. 83e echocardiogram (Table 1) may show an incomplete ventricular apical obliteration in endomyocardial fibrosis 84 and hypereosinophilia syndrome. 85he laboratory tests usually performed are listed in Table 1.

Third clinical scenario
A 67-year old woman was admitted to our Division due to the acute onset of dyspnoea on mild exertion, peripheral oedema, dizziness and oliguria.
The family history was unremarkable.She had a personal history of hypertension, diabetes mellitus with chronic kidney disease and bilateral carpal tunnel syndrome.
On physical examination diminished sounds with S3 gallop and mitral systolic murmurs were heard, jugular venous pressure (JVP) was raised and peripheral bilat-eral pitting oedema was noticed.The laboratory studies showed severe kidney failure with proteinuria and very high values of NT-proBNP and troponin I.The ECG revealed low QRS voltages in limb leads and poor R-wave progression in the chest leads (Figure 3A).A brief and asymptomatic III degree AV block with spontaneous recovery to sinus rhythm was recorded on the 24-h ECG monitoring.The echocardiography showed concentric left ventricular hypertrophy, normal ejection fraction with low TDI velocities (Figure 3B), diffuse thickening of interatrial septum and atrioventricular valves, moderate pulmonary hypertension, restrictive pattern of diastolic LV filling and severe left atrial dilatation.
Some diagnostic red flags emerged: a history of bilateral carpal tunnel syndrome; a typical ECG pattern; a concentric biventricular hypertrophy with and valvular involvement on echocardiogram.All these Various form of amyloidosis exists and in each one the myocardial involvement is variable.When the suspicion of cardiac amyloidosis is present other diagnostic techniques can be used: cardiac MRI [86][87][88] and 99mTc-DPD scan [89][90][91] are sensitive test for the detection, characterization and differentiation of forms of cardiac amyloidosis.The 99mTc-DPD scan is an exquisite test for the transthyretin-related amyloidosis (ATTR) diagnosis, far less sensitive in AL amyloidosis.However, we could not perform neither cardiac MRI in this patient, because she was strongly claustrophobic, nor the 99mTc-DPD scan, because the test was not available at that time in our Department.
An echocardiogram with the speckle tracking analysis was repeated and showed the typical relative apical sparing pattern, 92 specific for cardiac amyloidosis (Figure 3C).
In order to support our diagnostic hypothesis, second level laboratory tests, consisting of urine and plasma protein immunofixation with free light chains, were performed and revealed elevated free λ light chains in blood and urine.
Nonetheless, a definitive diagnosis of amyloidosis requires histological evidence of specific amyloid deposition on tissue specimens.Than some biopsies with increasing degree of invasiveness were obtained.Fat pad biopsy stained negatively for amyloid with Congo red on polarizing microscopy but electron microscopy showed some fibrils formed by amyloid in small blood vessels.Moreover, immunoelectron microscopy permitted further characterization of the patient's amyloid λ free chains.
In this case we concluded for AL amyloidosis with severe heart involvement in the form of a restrictive cardiomyopathy, due to monoclonal gammopathy of undeterminated significance (MGUS).Than, a specific therapy with steroids and Bortezomib started (Figure 4).

Right ventricular cardiomyopathies
The right ventricular cardiomyopathies are myocardial disorders in which the right ventricular involvement is exclusive or predominant. 93Under this umbrella-term are grouped several disorders: inherited disorders, such as the arrhythmogenic right ventricular cardiomyopathy (ARVC), the endomyocardial fibrosis (EMF), the cardiac sarcoidosis and the cardiac amyloidosis.Also in acute myocarditis may mimic ARVC when it displays prevalent RV involvement.
In RV cardiomyopathies, the family history is important: the presence of family members affected and a family history of SCD or ICD implantation in pedigree analysis fosters the suspicion of ARVC. 94,95 personal history of ventricular tachycardia (VT) or ICD implantation in secondary prophylaxis is consistent with disorders such as ARVC, amyloidosis, sarcoidosis and myocarditis.No specific symptoms are known and the most of these conditions are asymptomatic or poorly symptomatic.
The physical examination gave specific clues just in ARVC (Table 2): the presence of palmoplantar keratoderma and woolly hair is typical in Naxos disease and in Carvajal syndrome, 96 clinical variants of ARVC.
Conversely, the ECG is a sensible tool that may present some diagnostic clues (Table 2): repolarisation abnormalities, such as inverted T waves in inferolateral leads, and intra-ventricular conduction delays, represented by QRS enlargement and epsilon waves, are useful red flags for ARVC diagnosis. 97,98In amyloidosis there The signal average ECG is a wide amplitude superficial ECG that permits to recognize the low amplitude late potentials at the end of the QRS complex. 99The late potentials are a hallmark of ARVC and help us in disease definition and in the differential diagnosis with mimicking conditions.
The echocardiogram is the first cardiovascular imaging method usually performed 100 but, for the clearest visualization of the RV, the best spatio-temporal resolution and possible myocardial characterization gave by the gadolinium administration, the CMR represents an indispensable tool in this setting (Table 2).In ARVC the tissue analysis shows on T1 weighted images the myocardial fatty infiltration, a specific diagnostic clue observed as areas of high signal intensity. 101,102In the early stage of EMF are frequently described isolated thrombi or RV apical obliteration, as a manifestation of massive endomyocardial thrombus formation, with RV diastolic dysfunction and tricuspid valve involvement, while the tissue analysis shows a typical circumferential sub-endocardial hyperenhancement.In the later stage, the cavity obliteration extends over the apex disorganizing the ventricular architecture: a severe spontaneous contrast in RV cavity and a giant right atrium are then described. 103In cardiac amyloidosis, sarcoidosis and myocarditis the CMR findings are the same described for the dilated phenotype.
The laboratory tests usually performed in this setting are listed in Table 2.
As for other cardiomyopathies, diagnostic techniques may be necessary to achieve the diagnosis: the cardiac nuclear scintigraphy and the endomyocardial biop-

Fourth clinical scenario
A 62-year old man was visited in our ambulatory due to the recent onset of shortness of breath, tiredness and peripheral oedema.He had a previous cardiologic consultation in which a biventricular systolic dysfunction was noticed on echocardiogram.He had a family history of CAD and sudden cardiac death on his paternal side of the family.In his personal history he had a treated hypothyroidism and an ICD implantation two year before, following an episode of syncope with evidence of ventricular tachycardia on ECG.
On physical examination raised JVP and marked bilateral ankle swelling were noticed.
The ECG showed paced rhythm with normal AV, epsilon wave widespread with normal R-wave progression and T-wave inversion on anterior and inferior leads.
The echocardiogram showed a markedly dilated RV cavity with severely impaired systolic function; mildly impaired LV function (EF 45%), mainly due to abnormal septal motion; moderate tricuspid regurgitation, due to a combination of dilated RV annulus and ICD lead, causing coaptation defect, with high pulmonary pressure and severely dilated RA.
A coronary angiogram was performed previously, after the syncopal episode, and was unremarkable.The laboratory screening showed raised inflammatory markers.
Based on the basic clinical approach, a biventricular myocardial disorder with a predominant RV involvement, was suspected.The conditions considered were ARVC, cardiac sarcoidosis and myocarditis.The family history of SCD and the personal history of ICD implantation due to VT were suggestive of an inherited and potentially arrhythmogenic disorder, mainly ARVC, but did not exclude the other possible diagnosis.The complaint of dry cough, in presence of normal chest X-ray and in absence of other causes immediately excludible, suggested the diagnosis of cardiac sarcoidosis.The epsilon waves and the inverted Twaves in inferolateral leads were specific red flags for ARVC with biventricular involvement.The raised inflammatory markers suggested a coexisting or determining inflammatory condition, mainly sarcoidosis and myocarditis.
Then, to explore a possible inflammatory-based aetiological cause, a 18F-FDG-PET scan was performed and showed a mild and non-specific diffuse biventricular enhancement.The CMR with LGE was performed in order to differentiate between cardiac sarcoidosis and ARVC: the presence of high RV volumes with low systolic function, the LV involvement with mild systolic dysfunction, the absence of mediastinal lymphadenopathy and LGE, all suggested the presence of ARVC instead of cardiac sarcoidosis.
Thus, the presence of conduction abnormalities on ECG and of structural RV abnormalities on cardiovascular imaging techniques, fulfilled the 2010 Task Force Criteria for the diagnosis of AVRC. 104hus, we concluded for ARVC with biventricular involvement in a patient with ICD implantation for symptomatic VT performed before the definitive diagnosis.The genetic testing was proposed but refused by the patient.
A significant family history of HCM, premature sudden cardiac deaths,

Figure 1 .
Figure 1.A) ECG showing T-wave inversion in precordial and lateral leads; B) Low image quality transthoracic echocardiography: apical 4-chamber view showing an apical mass d; C) Contrast echocardiography with lung penetrating agent showing apical hypertrophy.

Figure 2 .
Figure 2. A) Apical 4-chambers view on echocardiography showing left ventricular dilatation; B) Left ventricular dilatation confirmed on cardiac magnetic resonance image; C) Mild and diffuse left ventricular enhancement showed on 18F-FDG-PET scan.

Figure 3 .
Figure 3. A) ECG showing a pseudo-infarct pattern; B) Transthoracic echocardiography showing restrictive filling pattern at mitral inflow spectral Doppler signal and low systolic and diastolic peak velocities on tissue Doppler imaging; C) Apical sparing pattern showed on speckle tracking imaging.

Figure 4 .
Figure 4. A) ECG showing an epsilon wave widespread with T-wave inversion on inferolateral leads; B) Transthoracic echocardiography: apical 4-chamber showing markedly dilated right cavities.

Table 2 . Diagnostic clues fostering the suspicion of specific causes of dilated and right ventricular cardiomyopathies.
PH, RV involvement, septum with LGE, soluble iL-2R, IV blocks, ventricular normal to dilated cavities, oedema on T2-w imaging, lysozyme, ACE, arrhythmias (VT, VF).