Association of atrial tachyarrhythmia, heart block, and right ventricular dysfunction: a case report and review of literature

Abstract

Background

The association of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease is rarely reported in literature. Previous case reports include right ventricular dysfunction associated with sudden cardiac death and ventricular arrhythmia. Other case reports with similar clinical presentation triad differ by either left ventricular involvement or having an abnormal presentation of systemic diseases.

Case presentation

We report a case series of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease in a single family. The proband in this case series is a 70-year-old Egyptian male who presented to our care for dual-chamber pacemaker generator replacement. He had the pacemaker for 10 years because of complete heart block. Device interrogation showed recorded paroxysmal atrial fibrillation episodes. Transthoracic echocardiography showed normal left ventricle internal dimensions and ejection fraction, dilated right ventricle with preserved systolic function, severe tricuspid regurgitation, and systolic pulmonary artery pressure of 40 mmHg. On reviewing his old records, there was no right ventricular affection 10 years ago; progressive right ventricular dysfunction occurred over the last decade. Despite guideline-directed medical therapy, the patient’s clinical status deteriorated, and surgical tricuspid valve replacement was performed with a tissue valve. Since the surgical intervention, his clinical status and functional capacity improved, and repeated echocardiography showed no tricuspid regurgitation with persistence of the right ventricular dilatation but with normal right ventricular function. On reviewing his family history, the triad of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease occurred in affected family members with various presentations. There was no left ventricular involvement, no history of ventricular arrhythmias in any of the affected members, and there was no history of sudden cardiac death across all three generations.

Conclusion

Familial clustering of right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease do exist. This constellation of findings is not well described in literature. Further reporting of similar cases and investigating of genetic bases are required.

Background

Familial cardiomyopathy is a well-described clinical entity [1]. However, these patients typically present with dilated cardiomyopathy (DCM) with left ventricular involvement. The constellation of (right ventricular (RV) dysfunction, atrial tachyarrhythmias (ATAs), and cardiac conduction system disease (CCSD) is rarely reported in literature. Previous case reports include additional manifestations as ventricular arrhythmia, sudden cardiac death, or concomitant left ventricular (LV) involvement, which are not present in our case series.

Case presentation

Proband: family member generation II no. 4

A 70-year-old Egyptian male presented to our care for dual-chamber pacemaker generator replacement. He had the device implanted for 10 years for complete heart block. Device interrogation showed that he is pacemaker-dependent with recorded paroxysmal atrial fibrillation (PAF) episodes. He had no risk factors for coronary artery disease. Clinical examination showed elevated jugular venous pressure, enlarged tender liver, and bilateral lower limb pitting edema. Basal metabolic panel, lipid profile, inflammatory markers, and iron profile were within normal limits. Transthoracic echocardiography showed normal LV internal dimensions and ejection fraction, dilated right RV with preserved systolic function (RV basal diameter in apical four-chamber view was 5.4 cm; tricuspid annular plane systolic excursion (TAPSE) 17 mm; and tricuspid valve S´ wave velocity (TV S´) 10 cm/s), severe tricuspid regurgitation (TR), and systolic pulmonary artery pressure of 40 mmHg. On reviewing his old records, there was no RV affection 10 years ago progressive RV dilatation occurred over years. Over 3 years of follow-up, he required direct current (DC) cardioversion for persistent atrial fibrillation twice. Despite constantly optimizing his medical treatment that included diuretics, beta-blockers, SLGT2i, and amiodarone, the patient’s clinical status deteriorated over time with progressive manifestations of right-sided heart failure, decrease in the functional capacity (New York Heart Association (NYHA) class III), and rising serum creatinine. Eventually, he underwent surgical tricuspid valve replacement with a tissue valve. Since the surgical intervention, his clinical status and functional capacity improved and repeated echocardiography showed no tricuspid regurgitation (TR) with persistence of the RV dilatation but with normal RV function.

Family members were screened for similar cardiac affections, and there was a triad of progressive RV dilatation/failure, ATAs, and CCSD in seven family members within three generations. Table 1 presents various presentations, cardiac interventions, and outcomes of affected family members. It is worth mentioning that there was no LV involvement or history of ventricular arrhythmias (VAs) in any of the affected family members, and there was no history of sudden cardiac death (SCD) across all three generations. Excluding tissue characterization owing to unavailability of endomyocardial biopsy, none of the affected family members satisfied the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) on the basis of the modified task force criteria [2]. A family pedigree is depicted in Fig. 1. An electrocardiogram (ECG), echocardiography, and cardiac magnetic resonance imaging of two different affected family members are depicted in Fig. 2. The timeline of the proband’s clinical events is depicted in Fig. 3.

Table 1.

Affected family members, their presentations, and outcomes

Family members				Presentation and outcomes
Generation	Number	Age at presentation (years)	Gender	Heart block	RV dysfunction	Atrial arrhythmia	Cardiac intervention	Death
II	4	70 (proband)	Male	+	+	Afib	Dual-chamber pacemaker and tricuspid valve replacement	–
Ӏ	2	Unidentified	Female	+	–	–	Pacemaker	+ (Non-cardiac etiology above the age of 80 years)
II	6	66	Female	+	–	–	Dual-chamber pacemaker	–
II	14	67	Female	–	+	Afib	–	–
III	18	32	Male	+	+	Atrial flutter/Afib	Dual-chamber pacemaker, complex flutter ablation, and tricuspid valve replacement	–
III	19	46	Female	+	+ Dilated RV with preserved function	Afib	Dual-chamber pacemaker	–
III	20	40	Male	+ Wenckebach AV block	–	Atrial flutter	Ablation of CTI-dependent flutter	–

Afib atrial fibrillation, CTI cavo-tricuspid isthmus, AV block atrioventricular block

Fig. 1.

Family pedigree (generations are marked by numbers I, II, and III on the left; affected family members are color-coded according to clinical presentation; proband is marked with an arrow) CCSD cardiac conduction system disease. Black line over circle numbered 2 in first generation means the patient deceased

Fig. 2.

A Cardiovascular magnetic resonance imaging of patient G III no. 20 presenting with atrial tachyarrhythmias and cardiac conduction system disease showing biatrial dilatation (likely due to concomitant hypertension) and normal ventricles. B Electrocardiogram of the same patient showing biatrial enlargement and prolonged PR interval. C Two-dimensional transthoracic echocardiography of patient G III no. 18 presenting with right ventricular dysfunction, atrial tachyarrhythmias, and cardiac conduction system disease in an apical four-chamber view showing dilated right atrium with dilated right ventricle diastolic dimensions. D shows continuous Doppler tracing of a repaired tricuspid valve in the same patient showing an increased flow with mean pressure gradient of 5 mmHg

Fig. 3.

Time line of proband’s clinical events; DDD dual-chamber pacemakerPG pulse generator, TR tricuspid regurgitation, TV tricuspid valve

Discussion

Familial cardiomyopathy is a well-described clinical entity. To date, more than 100 genes have been implicated it its pathogenesis [3]. However, these patients typically present with DCM with LV involvement. DCM affects approximately 1/250 individuals and is frequently associated with additional cardiac or noncardiac phenotypic feature that point to a particular genotype [4]. Among common cardiac phenotypic features associated with DCM are ATAs and CCSD.

The association between DCM and ATAs has been reported with several gene mutations, including FLNC, LMNA, RBM20, and SCN5 A genes. Such cases appeared to be rare until data from studies began to show that loss-of-function variants in TTN were associated with atrial fibrillation (AF) [5], pointing to the value of screening patients with unexplained AF for disease-associated variants in both cardiomyopathy and arrhythmia genes [6, 7]. A recent study sequenced 1293 patients with early onset AF for genes included on commercially available cardiomyopathy and arrhythmia panels—a disease-associated variant was found in 10.1% patients overall and in 16.7% with AF onset before 30 years [8].

The association between DCM and CCSD has been reported with several gene mutations, including DES, DSP, LDB3, LMNA, MYH6, MYH7, and SCN5 A genes. LMNA variants are associated with progressive CCSD as well as with AF and VAs, perhaps due to their predilection to cause septal fibrosis. A certain grade of CCSD is present at the time of diagnosis in 38–78% of LMNA cardiomyopathy. By the time VA occurs, most patients have some degree of conduction system disease. Complete heart block may occur several years before evidence of DCM, which develops in almost all patients who reach their seventh decade [9, 10].

Inherited right ventricular cardiomyopathy is commonly encountered in clinical practice; ARVC is the prototype of this clinical presentation. ARVC diagnosis is established through applying the modified task force criteria published in 2010 [2]. Progressive RV dilatation/failure, ATAs, and CCSD can occur in patients with ARVC; however, these clinical presentations neither occur commonly nor early in the course of the disease. In the present report, none of the affected family members satisfied the diagnosis of ARVC on the basis of the modified task force criteria. In this clinical context, the differential diagnosis of ARVC includes Uhl’s disease, RV noncompaction cardiomyopathy, and restrictive cardiomyopathies—all were excluded through the clinical presentation and imaging, including echocardiography and cardiovascular magnetic resonance (CMR) imaging, as clinically indicated.

The present report describes a cluster of seven patients with inherited RV dilation/failure, CCSD, and ATAs. This familial constellation of findings is rare, and in the absence of LV involvement, congenital heart defects, LV hypertrophy, and ventricular pre-excitation or noncardiac phenotypes, such as muscular dystrophies, bone defects, hearing impairment, juvenile diabetes, dysmorphism, and metabolic or storage diseases, this phenotype does not point to any previously described genotype. Table 2 summarizes similar reports in literature [11–18]. At least some of the early reports, particularly those involving patients presenting with VAs, SCD, or LV involvement, could be early reports of ARVC or LMNA gene mutations [11, 12]. Others had confirmed alternative diagnoses [15, 17].

Table 2.

Literature review of similar reports

Study	Year of publication	Population	RV affection	Conduction system disease	Arrhythmias	Diagnosis and follow-up
Ibsen et al. [11]	1985	Three members affected (one female and two males) 33 normal family members screened	Dilated RV (two patients), impaired LV function (one patient)	+	Atrial arrhythmias	Heart failure first, then arrhythmia and heart block; postmortem biopsy carried out for proband showed RV hypertrophy with fiber attenuation, fibrosis of replacement type, and fatty infiltration
Graber et al. [12]	1986	One family (history of 214 members and six generations was obtained); proband and other 9 members were affected	Biventricular failure	+	Atrial and ventricular arrhythmias	LV affection and ventricular arrhythmias (this could be an early report of LMNA mutation)
Caglar et al. [13]	1993	One patient	Isolated RV cardiomyopathy	+ Transient	+ Transient	Transient atrial flutter with heart block; patient refused pacing and was lost to follow-up
Blondheim et al. [14]	2000	Two sisters	+ Idiopathic RA dilatation and RV enlargement	+ One had complete heart block and VVI pacemaker	–	Presentation with heart block at younger age
Doi et al.[15]	2003	Two sisters	+ Isolated RV failure	+	–	Diagnosed as Fabry disease by endomyocardial biopsy, absence of extracardiac affection, LV hypertrophy diagnosed by echocardiography, restrictive pathology by catheterization
Biočić et al. [16]	2010	Brother and sister	Idiopathic RA enlargement, progressive RV dilatation at follow-up with normal LV function in first patient; his sister showed normal RV function and mild impairment of LV systolic function	+ Complete heart block (first patient)	+ Atrial fibrillation	SCD of the first patient (no biopsy) after short follow-up
Vakil et al. [17]	2014	One female patient	+ Isolated RV failure	+ (Complete heart block)	+ Atrial flutter	Diagnosed by pathology after transplantation, as isolated RV sarcoidosis
Figuero et al. [18]	2015	One male	Isolated RV cardiomyopathy	–	–	CMR (no scars, no ARVC), TEE: no shunts, right heart catheterization (RHC) and pulmonary angiography (PA) (excludes pulmonary hypertension (PH)); follow-up for 2 years: the patient is asymptomatic, and RV still dilated

On the basis of the pattern of inheritance that involved more than one generation and affected both genders, it is likely that the affected gene is inherited in an autosomal dominant pattern with incomplete penetrance. The present report is limited by the lack of genetic testing of the affected family members. The extensive genomic testing required to identify a de novo genetic mutation with the currently limited resources precluded including genetic data in this primary report.

Conclusion

We report familial clustering of right ventricular dysfunction associated with atrial arrhythmia and progressive cardiac conduction system disease. This constellation of findings is unique as there was no LV affection or family history of SCD. While responsible gene mutation is yet to be identified, further reporting of similar cases is recommended.

Abbreviations

RV

Right ventricular

ATAs

Atrial tachyarrhythmias

CCSD

Cardiac conduction system disease

PAF

Paroxysmal atrial fibrillation

LV

Left ventricle

EF

Ejection fraction

TR

Tricuspid regurgitation

VAs

Ventricular arrhythmias

SCD

Sudden cardiac death

ARVC

Arrhythmogenic right ventricular cardiomyopathy

Author contributions

Conception and design—Ahmed El-Damaty. Administrative support—Ahmed El-Damaty. Provision of study materials or patients—Ahmed El-Damaty. Collection and assembly of data—Mohamed Muharram, Sherien Samy, and Ahmed Shaaban. Data analysis and interpretation—Ahmed El-Damaty and Mohamed Muharram. Manuscript writing—all authors. Final approval of manuscript—all authors.

Funding

None.

Availability of supporting data

All data generated or analyzed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

The study protocol was approved by the Ethical Committee of the Faculty of Medicine, Al-Azhar University. Written informed consent to participate was obtained from all reported patients.

Consent for publication

A next of kin gave a written informed consent for the deceased patient. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.