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Hypertrophic Cardiomyopathy with Extensive Left Ventricular Fibrosis and Severe Mitral Regurgitation

Case presented by Working Group on Myocardial and Pericardial Diseases

The Case

Presented by: Regina Votavová, Lubor Goláň, David Zemánek and Aleš Linhart
2nd Department of Internal Cardiovascular Medicine. First Medical Faculty, Charles University in Prague. General University Hospital in Prague. Czech Republic.

Case presentation

In 2013, a 53 years-old man has been primarily diagnosed with HCM after surviving an episode of cardiopulmonary resuscitation due to sustained monomorphic ventricular tachycardia. After being investigated, the patient was implanted with an ICD indicated as a secondary prevention measure. Magnetic resonance imaging (CMRI) before the implantation has shown an extensive fibrosis and thinning of the posterolateral wall (Figure 1) and large area of gadolinium late enhancement (LGE) within this part of the heart.

Figure 1: MRI showing extensive late gadolinium enhancement within the middle layer of the myocardium of the posterolateral wall (arrows). This type of replacement fibrosis is characteristic for advanced AFD associated cardiomyopathy.

A scar due to coronary artery disease was suspected but coronary angiography demonstrated only a mild stenosis of the first diagonal branch.
After ICD implantation he had suffered two episodes of ventricular tachycardia (VT) in 2013 terminated with antitachycardia pacing, one series of adequate ICD discharges terminating a VT after a third discharge and a series of inadequate discharges due to the T waves oversensing in 2014. In the past he had several deep vein thrombosis and is being on warfarin since 2009. He was repeatedly admitted to the hospital for progressive congestion including worsening of dyspnea and development of peripheral leg edemas. The last hospital stay occurred in May 2015. Of note, after the discharge the patient had a transient elevation of serum creatinine from baseline values of 106 μmol/l up to 146 μmol/l. At that time he had an INR elevation to 3.78.

At present, the patient complains of dyspnea NYHA class II-III, he suffers from nycturia (about three times per night), and mild ankle edemas, does not report any chest pain palpitations of recent syncope. He works manually; does not smoke but admits drinking about one liter of wine every second day and being a bit negligent with the prescribed treatment. His recent treatment included warfarin  9 mg o.d., perindopril 5 mg o.d., metoprolol succinate 50 mg o.d., furosemide 40 mg o.d., spironolactone 25 mg o.d. and omeprazole 20 mg o.d..

His family history is not significant. His mother is 79 and healthy, his father died at age of 84 from diabetes complications. His brother, 54 years old, is suffering from repeated deep vein thrombosis. His daughter lives abroad without keeping contacts with the family.

The physical examination at admission to our department in July 2015 reveals no skin abnormalities, no signs of pulmonary or peripheral congestion, regular heart rate, a systolic murmur 4/6 with maximum intensity above the apex propagating to the axilla. His blood pressure at admission was 115/70 mmHg, HR 62/min, SpO2 99%.

ECG (Figure 2) revealed a sinus rhythm 75 beats per minute with premature ventricular and supraventricular complexes; the PQ interval 150 ms, QRS complex 114 ms, QTc 437 ms, incomplete right bundle branch and possibly left posterior fascicular block; the presence of Q waves suggestive of posterolateral scar and diffuse repolarization changes with T wave inversions. 

Figure 2: ECG showing sinus rhythm at 75 beats per minute with premature ventricular and supraventricular complexes; the PQ interval 150 ms, QRS complex 114 ms, QTc 437 ms, incomplete right bundle branch and possibly left posterior fascicular block; the presence of Q waves suggestive of posterolateral scar and diffuse repolarization changes with T wave inversions. 

Echocardiography shows significant LV hypertrophy within all myocardial walls except the basal segments of the posterolateral wall with an apparent myocardial thinning and akinesia (Figure 3 and 4).

Figure 3: Echocardiography – parasternal long axis view showing hypertrophied interventricular septum and thinned segment of the posterior wall (arrows).

Figure 4: Echocardiography – parasternal short axis view showing hypertrophied walls except a thinned segment of the posterolateral wall (arrows).

There is a significant systolic restriction of the mitral leaflets movement (particularly of the posterior one) leading to a severe mitral regurgitation (RV 75 ml, ERO 60 mm2) propagating to pulmonary veins with apparent S1 wave inversion (Figure 5 and 6).

 Figure 5: Transesophageal echocardiography (left) showing the extent of mitral regurgitant flow and large vena contracta and pulmonary venous flow (right) recorded from apical four chamber view showing an inversion of S1 wave.

Figure 6: Echocardiography showing PISA quantification of the mitral regurgitation – effective regurgitant orifice (ERO) was calculated at 0.6 cm2 and regurgitant volume (RV) at 75 ml.

There is a substantial left atrial dilatation (Figure 7), right ventricular hypertrophy and mild pulmonary hypertension.

Figure 7: Volumetric quantification of left atrium showing a severe left atrial dilatation.

Laboratory results of the patient show a mild elevation of serum creatinine at 116 mol/l (eGFR calculated at 57 ml/min/1.73m2 and 61 ml/min/1.73m2 by MDRD and CKD-EPI equations, respectively) and proteinuria evaluated by 24hours urine collection at 1.17 g/24 hours. His liver functional tests show marked elevation of GGT and mild increase in AST and ALT.


  1. What diagnosis do you suspect:
    • Unrecognized coronary artery disease in an HCM
    • Post inflammatory changes in an HCM
    • Anderson – Fabry disease
    • Danon disease
  2. What would be your next steps:
    • Repeated coronary angiography
    • Endomyocardial biopsy
    • Sarcomeric genes sequencing
    • Measurement of a-galactosidase A activity

The solution of the previous case of the month: Death on stage: a 26-year old actress with sudden cardiac death while performing on stage.

Presented by Anna Neugebauer, Barbara Pfeiffer, Hubert Seggewiss, Angelos G. Rigopoulos
1st Department of Internal Medicine, Leopoldina Hospital, Schweinfurt, Germany

How did we treat the patient?

On the second day the patient was extubated and showed complete neurological recovery.  She was treated as an acute myocarditis and put on metoprolol 47.5 mg / day while she further stayed under close rhythm surveillance. In transthoracic echocardiography the left ventricular function improved during the hospital course and was only mildly reduced before discharge (after 37 days in hospital). In rhythm monitoring several events of non-sustained ventricular tachycardia were documented. ICD implantation was considered for secondary prevention of sudden cardiac death. Nevertheless, in order to avoid further exposition of the fetus to radiation we decided to defer ICD implantation and the patient received a life vest before discharge until delivery.

She was then discharged on the above therapy and remained under cardiological and obstetrical ambulatory follow-up. An ICD was implanted after delivery.

Which further clinical diagnostics are recommended?

After a detailed history taking, a familial heart disease was assumed:  her father had received an ICD due to ventricular arrhythmia, the sister of her father died suddenly at the age of 50 years and the paternal grandfather died suddenly at the age of 37 years.
After delivery a coronary angiography was performed, which showed no coronary heart disease or coronary abnormality. Throughout follow-up, no hint for Brugada or long-QT syndrome was found.
Due to the new-onset heart failure with left ventricular wall hypokinesia and the new-onset of ventricular arrhythmias our patient underwent right ventricular myocardial biopsy which revealed no active myocarditis or storage disease, but contraction band myofibrillar degeneration after temporary ischemia.
Because of the suspicion of a familial cause of a dilated cardiomyopathy with an ominous prognosis, genetic testing was performed, which gave finally proof of DCM by a non-described mutation in lamin A/C-gene (Trp467Stop heterozygote).

How should we treat the baby?

From a radiological point of view the effective uterus dosage (CCT and CT angiography at day of admission) was lower (actually only thoracic imaging is relevant for fetus exposure) than the uterus threshold dose (50mSv).
From an obstetric point of view no harm of the fetus was suspected because of the all-or-none law of early gestation.
Therefore the patient carried the child to term under close cardiological and obstetrical surveillance. Because of continuing NSVTs the patient was kept the last 3 weeks in-hospital with rhythm monitoring until delivery and finally gave birth to a healthy boy by caesarean section. 

How was the further clinical outcome of this patient?

The patient had a familial LMNA-associated DCM with worsening left ventricular function which signifies a poor prognosis. In brief, in a period of 7.5 years after the initial event she experienced the following:

  • Several effective appropriate ICD-shocks because of ventricular tachycardia
  • Second degree AV-block Mobitz II (thought to be due to Lyme-borreliosis
  • Upgrade to biventricular ICD because of worsening heart failure
  • Thyroidectomy due to amiodarone induced hyperthyroidism
  • Atrial fibrillation 6,5 years after the initial presentation
  • Transitory ischemic attack and thrombotic occlusion of left arteria brachialis almost 7 years after the initial presentation
  • Further deterioration of the left ventricular function with severe global hypokinesia and diastolic dysfunction
  • Several hospitalisations because of cardiac decompensation
  • Finally, orthotopic heart transplantation and implantation of an IMEG-pacemaker 7,5 years after the initial presentation


This is a case of severe familial DCM due to a newly described lamin A/C-gene mutation with first manifestation during pregnancy.

The causes of familial DCM, which account for as many as 35% of all cases of idiopathic cardiomyopathies are mutations in genes that encode proteins of a wide variety of cellular components and pathways, mainly in the cytoskeletal/sarcomeric protein-encoding genes. Lamin A/C was found in roughly 6% of patients (1-3) and in 33% of patients presenting with conduction defects (4).   Mutation screening should be considered in patients with DCM, in particular in presence of ventricular tachycardia – as in the index case, conduction defects, mild dilatation with severe dysfunction, elevated CPK levels and skeletal muscle involvement (5).

The prognosis for mutation carriers is significantly worse because of a higher cardiovascular mortality caused by sudden cardiac death (because of life threatening arrhythmias) or heart failure. Identification of mutation carriers may lead to early prevention of SCD. Currently, there is no specific cure for laminopathies and treatment is largely symptomatic and supportive.


  1. Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol 2011; 57(16):1641-1649.
  2. Parks SB, Kushner JD, Nauman D, Burgess D, Ludwigsen S, Peterson A, Li D, Jakobs P, Litt M, Porter CB, Rahko PS, Hershberger RE. Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy. Am Heart J 2008; 156(1):161-169.
  3. Perrot A, Sigusch HH, Nagele H, Genschel J, Lehmkuhl H, Hetzer R, Geier C, Leon Perez V, Reinhard D, Dietz R, Josef Osterziel K, Schmidt HH. Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: demand for strategies in the management of presymptomatic lamin A/C mutant carriers. Eur J Heart Fail 2006; 8(5):484-493.
  4. Arbustini E, Pilotto A, Repetto A, Grasso M, Negri A, Diegoli M, Campana C, Scelsi L, Baldini E, Gavazzi A, Tavazzi L. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease. J Am Coll Cardiol 2002; 39(6):981-990.
  5. Cattin ME, Muchir A, Bonne G. 'State-of-the-heart' of cardiac laminopathies. Curr Opin Cardiol; 28(3):297-304.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.