Isolated left ventricular apical hypoplasia: Systematic review and analysis of the 37 cases reported so far

Abstract

BACKGROUND

Isolated left ventricular apical hypoplasia (ILVAH), also known as truncated left ventricle (LV), is a very unusual cardiomyopathy. It is characterised by a truncated, spherical, and non-apex forming LV. The true apex is occupied by the right ventricle. Due to the rarity of the disease, just a few case reports and limited case series have been published in the field.

AIM

To analysing the so far 37 reported ILVAH cases worldwide.

METHODS

The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022.

RESULTS

The majority of cases reported occurred in males (52.7%). Mean age at diagnosis was 26.1 ± 19.6 years. More than a third of the patients were asymptomatic (35.1%). The most usual clinical presentation was breathlessness (40.5%). The most commonly detected electrocardiogram changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death.

CONCLUSION

ILVAH is a multifaceted entity with a so far unpredictable course, ranging from benign until the elderly to sudden death during adolescence.

Key Words: Isolated left ventricular apical hypoplasia, Truncated left ventricle, Electrocardiography, Echocardiography, Cardiac magnetic resonance imaging, Heart failure

Core Tip: The manuscript is focused on an interesting topic, e.g. a rare form of cardiomyopathy which is called isolated left ventricular hypoplasia or truncated left ventricle. The so far 37 reported cases worldwide have been reviewed and analysed to help clinicians in the difficult management of this extremely rare congenital heart disease. Nice images from our personal archive have been added.

INTRODUCTION

Isolated LV apical hypoplasia (ILVAH) is an extremely rare and unclassified cardiomyopathy that has been recognized as a distinct entity since 2004[1]. ILVAH is also known as truncated left ventricle (LV). It is a very unusual cardiomyopathy which can be easily detected on echocardiography. It is characterised by a truncated, spherical, and non-apex forming LV with some degree of systolic dysfunction[2]. The true apex is occupied by the right ventricle, which wraps around the distal LV and whose systolic function is usually normal[2]. ILVAH is usually not accompanied by other abnormalities[3]. Its diagnosis is often refined by means of computed tomography or cardiac magnetic resonance imaging (MRI)[4]. Clinical presentation varies a lot, ranging from the lack of symptoms to fatigue, breathlessness, palpitations, chest pain, syncope[5,6]. The death of an adolescent patient was reported in literature. He suffered from arrhythmia with fulminant cardiac insufficiency and non-responsive to therapy pulmonary hypertension[7].

Due to the rarity of the disease, just a few case reports and limited case series have been published in the field. The aim of this paper is making a literature review concerning to so far reported cases of ILVAH with related features and outcomes.

MATERIALS AND METHODS

Search strategy

The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022. The MeSH (Medical Subject Headings) search terms were “case report” and/or “case series” and/or “isolated left ventricular hypoplasia” and/or “truncated left ventricle”. We excluded any animal studies, and papers with language other than English (Figure 1).

Figure 1 PRISMA flow diagram.

Study selection

The authors separately looked into the selected abstracts and evaluated whether they were eligible. Full-texts were checked when all the reviewers of the abstracts felt that the latter might match the inclusion criteria.

Data extraction

Information from the selected single case reports and case series were taken. The reported points were: age at diagnosis, gender, clinical presentation, electrocardiographic features, imaging (ultrasounds and cardiac MRI), associated cardiac abnormalities, therapy, and outcome.

Data presentation

Data were presented in the form of mean ± SD. Chi square test and Mann-Whitney U test were used to check statistical significance when needed. Statistical significance was set to P < 0.05.

RESULTS

Overall, 4427 potential single case reports of ILVAH/truncated left ventricle were detected on the PubMed and Scopus databases. Twenty were duplicates. Other 4378 papers were excluded after checking the abstract. The remaining 29 manuscripts were used for analysis of the patients’ features and disease outcome (Table 1)[8-29].

Table 1 List of the case reports and case series which have been published in the field.

Ref.	Patient’s age (yr)	Patient’s gender	Clinical presentation	Electrocardiogram	Echocardiography	MRI	Associated cardiac abnormalities	Therapy	Outcome
Dattani et al[8]	64	Male	Shortness of breath (NYHA III)	Complete left bundle branch block	Severe LV systolic dysfunction with global hypokinesis	Yes	Hypertension, hypercholesterolaemia and asthma	Furosemide, perindopril, bisoprolol and anticoagulation for the suspected mural thrombus	CRT
Chaowu et al[9]	22	Female	Palpitations	Atrial fibrillation, right axis deviation and T-wave abnormality	EF not reported	Yes	Dextro-transposition of the great vessels, patency of ductus arteriosus	Not reported	Serial follow-up
Vanhecke et al[5]	53	Female	Palpitations	Normal sinus rhythm, inferolateral T wave abnormalities and poor R wave progression	Severe LV systolic dysfunction (EF 35%), mitral valve regurgitation	Yes	Hypertension	Ace inhibitor, beta-blocker, and diuretics	Serial follow-up
Meléndez et al[10]	9	Female	Heart murmur. No symptoms	Not done	EF not reported	Yes	None	None	Serial follow-up
Marin et al[4]	3 months	Male	No symptoms	Not done	EF not reported	Yes	None	None	Serial follow-up
Patrianakos et al[11]	11	Female	Asymptomatic	Right axis deviation and decreasing R wave in precordial leads beyond V3	Mild-to-moderate decreased contractility with a restrictive filling pattern and mild mitral regurgitation	Yes	None	None	Serial follow-up
	35	Female	Previous peripartum pulmonary oedema	P mitrale, left axis deviation and decreasing R wave in precordial leads beyond V3	Mild-to-moderate decreased contractility with a restrictive filling pattern and mild mitral regurgitation	Yes	Atrial fibrillation	ACE inhibitor, beta blocker, and low-dose furosemide	Serial follow-up
Irving et al[7]	19	Male	Chest pain and palpitations	Atrial flutter and then ventricular fibrillation	LV systolic and diastolic function was severely impaired and RV function was also poor	Not done	Atrial and ventricular arrhythmias, refractory pulmonary hypertension	inotropic support (adrenaline, milrinone and vasopressin), inhaled nitric oxide and intravenous prostacyclin	Death
Braga et al[6]	66	Female	Atypical chest pain	Complete left bundle branch block	Mild LV systolic dysfunction (EF 48%), abnormal interventricular septal motion and elongated RV	Yes	Hypertension, dyslipidaemia and stable angina	None	Serial follow-up
Motwani et al[2]	63	Male	Exertional dyspnoea	Atrial fibrillation	Severely impaired LV systolic function	Yes	None	DC shock	Serial follow-up
Moon et al[3]	33	Male	Heart murmur. No symptoms	Right axis deviation, incomplete right bundle branch block, right atrial enlargement and RV hypertrophy	Good global LV systolic function	Yes	Mild infundibular pulmonary stenosis and moderate-to-severe aortic stenosis	None	Serial follow-up
Alizadeh Sani et al[12]	13	Male	Shortness of breath and chest discomfort	Right axis deviation and a low precordial voltage with poor R-wave progression	Severe LV systolic dysfunction, moderate mitral regurgitation, and enlarged left atrium	Yes	Developmental delay, family history of sudden cardiac death	Standard drugs for systolic heart failure	Serial follow-up
Zhao et al[13]	19	Male	Heart murmur. No symptoms	Right-axis deviation, poor R wave progression, and T wave abnormalities	Mild LV systolic dysfunction	Yes	RV outflow tract obstruction due to exaggerated rightward bulging of the basal-anterior septum during systole	ACE inhibitor and beta-blocker	Serial follow-up
Starmer et al[14]	62	Male	Shortness of breath	Atrial fibrillation and poor precordial R-wave progression	Severe LV systolic dyfunction	Yes	None	Standard heart failure therapy	Serial follow-up
Fernandez-Valls et al[1]	22	Female	Fatigue	Right axis deviation and low precordial voltages with poor R wave progression	Mild LV systolic dysfunction, moderate mitral regurgitation	Not done	None	Not reported	Serial follow-up
	46	Female	Shortness of breath	Right axis deviation and low precordial voltages with poor R wave progression	Mild-to-moderate LV systolic dysfunction	Yes	None	Not reported	Serial follow-up
	26	Male	Chest discomfort	Right axis deviation and low precordial voltages with poor R wave progression	Moderate-to-severe LV systolic dysfunction, moderate mitral regurgitation	Yes	None	Not reported	Serial follow-up
Hong et al[15]	34	Female	Chest discomfort	Q wave in leads V1-V4	Mild systolic dysfunction (EF 44%)	Yes	None	ACE inhibitor	Serial follow-up
Ding et al[16]	22	Female	Lethargy and shortness of breath	Fragmented QRS and undetermined axis	Severe LV systolic dysfunction	Yes	Non sustained ventricular tachycardia	Not reported	Serial follow-up
Orsborne et al[17]	17	Female	Chest pain	Not done	Normal LV systolic function	Yes	None	Not reported	Serial follow-up
Tumabiene et al[18]	21	Female	Severe respiratory distress	Atrial flutter	Mild LV systolic dysfunction	Yes	None	ACE inhibitor, beta blocker, diuretics	Serial follow-up
Ong et al[19]	11	Female	Heart murmur. Asymptomatic	Normal ECG	Normal LV systolic function	Yes	None	None	Serial follow-up
Flett et al[20]	37	Female	Pulmonary oedema	Left bundle branch block	Not reported	Yes	Non sustained ventricular tachycardia	Ace inhibitor, beta blocker, diuretics, amiodarone, coumarin	Serial follow-up
Meng et al[21]	24	Female	Exercise intolerance	Atrial fibrillation, right axis deviation, and T wave abnormalities	Severe LV systolic dysfunction (EF 34%), bi-atrial enlargement, mild-to-moderate mitral valve regurgitation	Yes	PDA, severe pulmonary hypertension	Anti-pulmonary hypertension agents	Serial follow-up
	5	Female	Exercise intolerance	Right axis deviation, and T wave abnormalities	Normal LV systolic function	Yes	None	None	Serial follow-up
	3	Male	Asymptomatic	T wave abnormalities	Normal LV systolic function	Yes	None	None	Serial follow-up
	13	Male	Asymptomatic	T wave abnormalities	Normal LV systolic function	Yes	None	None	Serial follow-up
	15	Male	Asymptomatic	T wave abnormalities	Normal LV systolic function, enlarged left atrium	Yes	PDA, severe pulmonary hypertension	Anti-pulmonary hypertension agents	Serial follow-up
Haffajee et al[22]	50	Male	Asymptomatic	Non-specific intraventricular conduction delay with lateral T-wave abnormal	Severe LV systolic dysfunction	Yes	PDA, S/P ligation	ACE inhibitor, beta blocker	Serial follow-up
Liao et al[23]	18	Male	Shortness of breath	Atrial fibrillation and left ventricular hypertrophy	Severe LV systolic dysfunction (EF 27%), mild mitral regurgitation	Yes	None	ACE inhibitor, beta blocker, diuretics, trimetazidine, levocarnitine	Serial follow-up
	2	Female	Asymptomatic	Normal ECG	Normal LV systolic function, mild mitral regurgitation	Yes	None	None	Serial follow-up
Maidman et al[24]	58	Male	Bradycardia and lightheadedness	Sinus bradycardia, right axis deviation, low QRS voltages, mild intraventricular delay	Mildly reduced LV systolic function (EF 45%)	Yes	Not reported	Not reported	Not reported
Ramamurthy et al[25]	16 months	Male	Asymptomatic	Raised ST segment, T wave inversion and q waves in lateral leads	Normal LV systolic function	Yes	None	None	Serial follow-up
Choh et al[26]	2	Male	Dyspnoea	Not reported	Normal LV systolic function	Yes	None	ACE inhibitor, beta blocker, diuretics	Serial follow-up
Skidan et al[27]	32	Male	Dyspnoea	Atrial fibrillation	Severe LV systolic dysfunction	Yes	LV non compaction	Ablation, ICD	Serial follow-up
Schapiro et al[28]	17	Male	Asymptomatic	Sinus bradycardia and nonspecific T wave changes	LV Systolic function not reported	Yes	None	Not reported	Serial follow-up
Mirdamadi et al[29]	19	Not reported	Mild dyspnoea	Normal ECG	Normal LV systolic function	Not done	None	None	Serial follow-up

MRI: Magnetic resonance imaging; NYHA: New York Heart Association functional class; LV: Left ventricle; CRT: Cardiac resynchronization therapy; EF: Ejection fraction; ACE: Angiotensin converting enzyme; RV: Right ventricle; DC: Direct current; ECG: Electrocardiogram; PDA: Patent ductus arteriosus.

The majority of cases reported occurred in males (52.7%; male-to-female ratio 1.12/1). Mean age at diagnosis was 26.1 ± 19.6 years; range 3 months-66 years). For male patients the mean age at diagnosis was 26.8 ± 22.2 years, whereas female patients were slightly younger (25.7 ± 17.5 years) at diagnosis. This difference was not statistically significant. More than a third of the patients were asymptomatic (35.1%). The most usual clinical presentation was breathlessness (40.5%). There are no statistically significant differences between genders in terms of symptoms/absence of symptoms. The most commonly detected electrocardiogram (ECG) changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%, most of all in the form of patency of ductus arteriosus with or without pulmonary hypertension. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death. The results of the review are summarised in Table 2.

Table 2 Isolated left ventricular apical hypoplasia patients’ main features (n = 37).

Male-to-female ratio	1.25/1
Mean age at diagnosis	26.1 ± 19.6 yr (range 3 mo-66 yr)
	Asymptomatic (35.1%)
	Breathlessness (40.5%)
ECG changes	T wave abnormalities (29.7%)
	Right axis deviation with poor R wave progression (24.3%)
	Atrial fibrillation/flutter (24.3%)
	Non sustained ventricular tachycardia (8.1%)
Diagnosis	By echocardiography (97.3%)
	By cardiac magnetic resonance (91.9%)
Reduced left ventricular ejection fraction	56.7%
Associated congenital heart disease	16.2%
Heart failure medical therapy	35.1%
Implantable cardioverter device	2.7%
Death	2.7%

ECG: Electrocardiogram.

DISCUSSION

From the case series analysis, there is a slight prevalence of ILVAH in males, though the disease is quite equally distributed between genders. The age of diagnosis is extremely variable, ranging from infancy to elderly. ILVAH is easily detected by echocardiography and diagnosis is confirmed by cardiac MRI (Figures 2 and 3).

Figure 2 Echocardiographic scan. A: Echocardiographic scan (4-chamber view) of the patient’s truncated left ventricle in diastole; B: Echocardiographic scan (4-chamber view) of the patient’s truncated left ventricle in systole; C: Enhanced contrast echocardiographic image (2-chamber view) showing that the right ventricle wraps around the deficient LV apex.

Figure 3 Cardiac magnetic resonance imaging. A: deficient non apex forming left ventricle; B: Axial view showing the anomalous origin of the papillary muscles in the flattened left ventricular apex; C: Sagittal view showing the right ventricle wrapping around the hypoplastic left ventricular apex.

On cardiac MRI the established features of ILVAH are four, namely: (1) A truncated and spherical LV shape with systolic and/or diastolic functions which are often impaired and rightward bulging of the interventricular septum in diastole; (2) Defective LV apex with adipose tissue infiltrating it; (3) Anomalous origin of the papillary muscles in the flattened LV apex; and (4) Elongation of the right ventricle wrapping around the deficient LV apex. In this report, we demonstrate these characteristic features with cardiac magnetic resonance imaging and summarize the existing information on isolated LV apical hypoplasia[5].

Differential diagnosis includes

(1) Hypoplastic left heart syndrome, which is characterised by underdevelopment of the aortic valve and artery, and the whole LV[30]. Mitral valve is stenotic or atretic in most of the cases[31]; (2) LV non-compaction, resulting from interrupted endomyocardial morphogenesis leading to LV dysfunction. It is characterised by a diffusely enlarged LV with a markedly trabeculated endocardium (“spongy” appearance)[32]. Interestingly, in Table 1, a patient with a unique combination on ILVAH and LV non-compaction is reported; (3) Congenital LV aneurysm, which is an idiopathic anomaly of the endocardial and myocardial layers, and LV diverticulum, belonging to a syndrome with multiple defects. However, LV is elongated rather than truncated with involvement of the papillary muscles and surrounding myocardium (as opposed to isolated apical involvement). These conditions are usually deadly early in life owing to associated intracardiac and extracardiac abnormalities[33,34]; and (4) Congenital LV dysplasia with or without right ventricular dysplasia. On cardiac MRI, at tissue characterisation, diffuse transmural fibrofatty replacement is noted, whereas in ILVAH it is predominantly apical[35,36].

Of note, isolated hypoplasia can also involve just the right ventricle, with lack of trabeculated apex[37].

The clinical course of ILVAH is variable. It can be benign, but complications, such as heart failure, supraventricular and ventricular arrhythmias, and pulmonary hypertension, have been described even in young patients[2,7,9]. Only one death has been reported so far[7].

A possible association with patency of ductus arteriosus is suggested by the analysis of the cases reported in this review.

ILVAH embryonic aetiology is purely speculative. However, in an article written not in English, and as such not included in the present analysis, a mutation of the lamin A/C gene (p.Arg644Cys) responsible for dilated cardiomyopathy was found associated to the disease[38].

CONCLUSION

On balance, the Authors hope that more cases may be published in the field to increase scientific knowledge on ILVAH. The latter is a multifaceted entity with a so far unpredictable course, ranging from benign until the elderly to sudden death during adolescence.

ARTICLE HIGHLIGHTS

Research background

Isolated left ventricular hypoplasia is an extremely rare form of cardiomyopathy.

Research motivation

We aimed at shedding light on the disease outcome.

Research objectives

The aim of this paper is making a literature review about to so far reported cases of isolated left ventricular apical hypoplasia with related features and outcomes.

Research methods

A literature review was carried out. The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022.

Research results

From the initial 4427 papers, 29 manuscripts were selected.

Research conclusions

The most usual clinical presentation was breathlessness (40.5%). There are no statistically significant differences between genders in terms of symptoms/absence of symptoms. The most commonly detected ECG changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%, most of all in the form of patency of ductus arteriosus with or without pulmonary hypertension. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death.

Research perspectives

The search strategy will be repeated after 10 years.