Introduction
Arrhythmogenic right ventricular cardiomyopa- thy/dysplasia (ARVC/D) has long been considered a disease with the risk of sudden cardiac death (SCD) [1, 2]. Life-threatening arrhythmias have been em- phasized as the main clinical feature and major ther- apeutic problem. In long-term follow-up studies, high rates of SCD have been reported, particularly in the young. Enormous progress has been made in re- cent years in the treatment of arrhythmias, changing the clinical outcome of ARVC/D. Implantable car- dioverter-defibrillator (ICD) implantation, radiofre- quency (RF) ablation or hybrid therapy for high-risk patients have significantly decreased the incidence of SCD in this group of patients. Worldwide awareness of the disease, advances in diagnostic procedures, preparticipation screening tests of young athletes, and family examinations have identified affected people early and enabled proper management, de- creasing the incidence of SCD as the first symptom of the disease. Success in the fight against SCD un- masked the problem of heart failure in patients with a longer disease history.
Heart Failure in ARVC/D
In the first follow-up studies of ARVC/D patients, heart failure was described as a rare event. In 1987
Blomstrom-Lundqvist et al. reported three cases of right heart failure among 15 patients with ARVC/D observed for 1.5-28 (mean 8.8) years [3]. Two of them died, one suddenly, the other due to conges- tive heart failure. The prognostic importance of heart failure was raised by Pinamonti et al. in 1992, who observed significantly higher mortality of patients who presented heart failure symptoms than in patients with arrhythmias (p=0.038) [4].
Heart failure was observed by Peters et al. in 13 pa- tients (11%) of a consecutive cohort of 121 pa- tients with ARVC/D over a period of 12 years [5].
Three of them died and three others underwent or were waiting for heart transplantation. A review of the literature up to 1999 indicated that 46% of car- diac deaths in clinical series of patients with ARVC/D were due to heart failure. Later this pro- portion began to change. Patients who died due to heart failure or underwent heart transplantation in large clinical series reported in 2003-2005 repre- sented 47%-66% of all cases of cardiac terminal events (Table 21.1) [5-8]. The mean age of patients who died because of severe pump failure or un- derwent heart transplantation was significantly higher than those who died suddenly both in the pathologic study of Basso et al. [9] and clinical se- ries of Peters [10].
Isolated right ventricular failure in ARVC/D, be- ing a result of dilatation, wall thinning and wall mo- tion dysfunction due to loss of cardiomyocytes,
MANAGEMENT OF HEART FAILURE
Elzbieta Katarzyna Wlodarska, Marek Konka
CHAPTER
21
Author No pts Follow-up HF % pts NSCD+OHT
(years, mean) No pts
Blomstrom-Lundqvist, 1987 [3] 15 8.8 20% 1
Peters, 1999 [5] 121 4-8 11% 3+3
Hulot, 2004 [6] 130 8 16% 5+2
Lemola, 2005 [7] 61 4.6 11% 2+5
Corrado, 2003 [8] 132 (ICD) 3.3 4
HF, heart failure; NSCD, nonsudden cardiac death; OHT, orthotopic heart transplantation; pts, patients Table 21.1 • Risk of nonsudden cardiac death in patients with ARVC/D – a systematic review of literature
represents a unique clinical situation where right heart failure is accompanied by low pulmonary pressure. As only 5 mm Hg is a sufficient pressure difference to provide adequate pulmonary flow, even severe damage of the right ventricle (RV) mus- cle has no apparent effect on hemodynamics. Para- doxical ventricular septum motion and prominent right atrial contraction provide functional com- pensation enabling normal physical activity for a long time. It is not well known what factors are a trigger for symptoms of right ventricular failure.
Left ventricle (LV) damage, superimposed my- ocarditis, atrial fibrillation, incessant ventricular tachycardia, and RV thrombosis are the most fre- quent mechanisms bringing mild RV heart failure symptoms.
Extensive damage of the RV leading to isolated RV failure symptoms is more frequent in the fatty variant of the disease, characterized by intensive fatty infiltration of the RV, reaching the endo- cardium and sparing the LV and septum (Fig. 21.1),
whereas biventricular failure mimicking dilated cardiomyopathy, is observed in the fibro-fatty vari- ant [11].
LV damage in patients with ARVC/D is known to be a risk factor of SCD as well as congestive heart fail- ure and non-SCD [7, 12, 13]. It is not unusual, par- ticularly in the fibrofatty variant of the disease. LV damage is observed in up to 55% patients and is char- acterized by focal hypokinesis at the apex and infero- posterior wall without severe chamber dilatation or, less frequently, by diffuse hypokinesis and moderate dilatation (Fig. 21.2) [14]. Macroscopic and histo- logical involvement of the LV was observed even in 76% of hearts with ARVC/D and was characterized by similar abnormalities to those found in the RV with a predominance of fibrosis [15]. In some genetic forms of the disease, LV damage appears early and leads to a clinical picture of dilated cardiomyopathy more frequently than in other forms of the disease.
In ARVD8 (desmoplakin gene mutation) LV in- volvement was seen in 43%, and heart failure symp- toms in 14% of patients [16]. LV damage is also a typ- ical feature of ARVD4, although severe manifestation of symptoms was reported only in patients involved in sport activities [17].
A possible mechanism of progressive right or biven- tricular failure, triggering apoptosis and necrosis due to Ca
2+ions overloading, is inflammation. Inflammatory cells (CD43-positive lymphocytes) are detected in two- thirds of cases with the fibrofatty variant of the disease [11]. Fontaine and colleagues demonstrated progres- sion of the disease due to superimposed inflammation [18]. Although viral myocarditis was demonstrated on- ly in single cases, increased susceptibility to infection
Fig. 21.1 • ARVC/D-fatty variant. a Heart removed at cardiac transplantation. b Two-dimensional echocardiogram of an apical four-chamber examination. Dilated right ventricle and regular diameter of left ventricle
a
b
Fig. 21.2 • Left ventricular (LV) involvement in ARVC/D.
Parasternal long-axis apical view. Apical aneurysm of LV (arrow)
with cardiotropic viruses in the diseased myocardium cannot be excluded [19].
The most important clinical marker of diffuse RV lesions with LV involvement, significantly associated with thromboembolism and heart failure, is atrial fib- rillation (AF). Supraventricular tachyarrhythmias are not rare in ARVC/D. Supraventricular tachycardia, paroxysmal atrial tachycardia, and AF are reported in clinical series observed in 14%-28% cases [7, 20-21].
Patients with supraventricular arrhythmias are older and have a longer disease duration. Whereas supraventricular tachycardias are probably a result of electrical instability of the right atrial myocardium, AF is tightly connected with advanced RV damage and often accompanied by LV impairment. Lack of atrium contraction worsens RV function, resulting in apparent heart failure symptoms [22].
There are very few reports available on throm- boembolic complications in patients with ARVC/D.
Most of them describe atrial thrombus formation in patients with the extensive form of the disease and with concomitant AF [23-26]. RV thrombosis is usually associated with severe dilatation of the RV and significant wall motion abnormalities [27]. The incidence of thromboembolic complications in ARVC/D seems to be less frequent than in patients with left ventricular failure of other causes (annual incidence: 0.48 vs. 1.9%, respectively) [27]. Despite their rare occurrence, these complications should not be underestimated because their clinical presen- tation is usually quite serious. Both pulmonary em- bolism with fatal outcome and severe heart failure in case of RV outflow tract thrombosis have been ob- served (Fig. 21.3). In patients with a severely dilated and akinetic RV, spontaneous echocardiographic contrast due to stagnant blood may be also ob- served (Fig. 21.4).
Management of Heart Failure
Management of patients with RV or biventricular heart failure includes diuretics, angiotensin-convert- ing enzyme inhibitors, and β-blockers. A new selec- tive aldosterone antagonist – eplerenone – has re- cently been reported to be effective in combined di- uretic treatment [28]. Beta-blockers, next to their antiarrhythmic activity, are known to inhibit apop- tosis [29]. Anticoagulant therapy is obligatory in pa- tients with AF and highly recommended in those with severe RV damage and spontaneous echocar- diographic contrast in the RV.
Fig. 21.4 • Apical four-chamber view. Cloud of echoes re- sulting from stagnant blood – echogenic blood – in right chambers
Fig. 21.3 • a Apical four-chamber view. Thrombus in the RV apex (arrows). b RV outflow tract with thrombus from parasternal long axis view (arrow). Ao, aorta; LV, left ventri- cle; RA, right atrium; RV, right ventricle. From [27]
a
b
