Heart failure related to adult congenital heart disease: prevalence, outcome and risk factors.
Arnaert S, De Meester P, Troost E, Droogne W, Van Aelst L, Van Cleemput J, Voros G, Gewillig M, Cools B, Moons P, Rega F, Meyns B, Zhang Z, Budts W, Van De Bruaene A.
ESC Heart Fail. 2021 Aug;8(4):2940-2950. doi: 10.1002/ehf2.13378. Epub 2021 May 7.PMID: 33960724 Free PMC article.
Take Home Points:
- Heart Failure is the leading cause of death in the ACHD population
- Though patients with ACHD are more frequently assessed for the transplantation, the actual number of those receiving transplantation remains low
- In this study, factors associated with a higher prevalence of heart failure included:
- moderate and severe complexity
- physiological severity Class C or D
- cyanosis (41% of patients with cyanosis had HF)
- Fontan circulation (30% had HF)
- Systemic RV (25% had HF)
- Independent factors related to the presence of heart failure in ACHD, included:
- age at latest follow-up [per 10 years increment; odds ratio 1.52]
- a history of infective endocarditis (odds ratio 4.11), a history of atrial arrhythmia (odds ratio 3.52)
- need for pacemaker implantation (odds ratio 2.66)
- end-organ dysfunction (odds ratio 2.41)
- NYHA class (odds ratio 9.28)
- heart rate (per 10 bpm increase; odds ratio 1.27)
- ventricular dysfunction (odds ratio 3.62)
- pulmonary hypertension severity (Odds ratio 1.66)
Commentary from Dr. Yonatan Buber (Seattle, USA), section editor of ACHD Journal Watch:
Heart failure (HF) has become a rapidly growing reason for hospitalization and is the leading cause of death in the ACHD patient population. Furthermore, the number of ACHD patients assessed for orthotopic heart transplantation increases although the number of listed patients remains relatively low, and for those unsuitable for transplantation the overall prognosis is poor.
The aim of the study was to assess the prevalence and outcomes of HF, to examine variables associated with HF and to identify differences between major anatomical/pathophysiological ACHD groups in a large cohort of ACHD patients followed for >1 year after 2010 in Leuven, Belgium.
Heart failure was defined as signs and/or symptoms requiring medical therapy plus one of the following:
- impaired ventricular function (systolic, diastolic or both) with elevated intracardiac pressures
- elevated B-type natriuretic peptide (BNP) or N-terminal BNP
- peak oxygen consumption in the lowest quartile according to published norms for ACHD subtypes
- unique HF manifestations in patients with a Fontan circulation (protein losing enteropathy, plastic bronchitis, Fontan systemic venous pressure ≥20 mmHg, and cardiac index <2)
A total of 3905 (52% male) ACHD patients with a mean age at last follow up of 35.4 ± 13.2 years were included. The breakdown of defect complexity was relatively typical, with 33% of patients having simple defects, 56% moderate, and 11% severe complexity defects. Based on the physiological severity classification, 18% were in physiological Stage A, 36% in physiological Stage B, 42% in physiological Stage C, and 4% in physiological Stage D.
248 patients (6.4%) had a HF diagnosis. Factors associated with higher prevalence of heart failure included moderate and severe complexity, physiological severity Class C or D, cyanosis (41% of patients with cyanosis had HF), Fontan circulation (30% had HF), and a systemic RV (25% had HF).
In a multivariable logistic regression analysis (with 8.6% missing cases), the following variables were independently related to the presence of ACHD-HF:
- age at latest follow-up [per 10 years increment; odds ratio 1.52]
- a history of infective endocarditis (odds ratio 4.11), a history of atrial arrhythmia (odds ratio 3.52)
- need for pacemaker implantation (odds ratio 2.66)
- end-organ dysfunction (odds ratio 2.41)
- NYHA class (ods ratio 9.28)
- heart rate (per 10 bpm increase; odds ratio 1.27)
- ventricular dysfunction (odds ratio 3.62)
- pulmonary hypertension severity (Odds ratio 1.66)
A remarkable changes of HF prevalence was noted to exist with age. The authors nicely show that HF prevalence increased with age from 2.3% in subjects aged 15–35 years to 6.8% in those age 35– 50 years and 21.9% in those aged >50 years. This age-related increase was consistent in all groups, but was especially evident in cyanotic patients, patients with a Fontan circulation, and patients with a systemic RV.
When associations with HF were evaluated within individual anatomic/physiologic groups, age, atrial arrhythmia, pacemaker, NYHA, and ventricular dysfunction were related to HF in all subgroups, whereas other variables were not.
For patients with a Fontan circulation, there was no difference between different types of Fontan circulation and having a dominant systemic RV was not associated with HF.
25.8% of the HF patients reached the combined endpoint of death, heart transplant, or VAD implantation. When 186 HF patients were matched with non-HF patients, the mortality rate ratio of HF to non HF patients was 4.67 (95%CI 2.36–9.27).
The main strengths of this study are the large cohort included in it, the precise definition of heart failure used, and the relatively abundance of data available on the cohort. The large number of patients allowed the authors to perform statistically feasible sub-group analyses and to delineate associations between the clinical variables within pre-defined subgroups. Overall, the prevalence of HF in this large cohort was 6.4%, and it was associated with a near 5-fold increase of death when HF patients were matched with non-HF patients, both figures being somewhat higher than in historic cohorts. The analysis performed for age as a risk factor for HF is particularly informative, showing a nearly 10-fold higher prevalence among patients aged >50 (22%) vs those aged 15-35 years (2.3%). The main limitations are those that typically accompany retrospective analyses of this sort, including reliance of medical records for clinical outcomes, the lack of data on medical therapy, exercise capacity, cross sectional imaging, socio-economic status and others.
Overall, this study is an important addition to the existing literature on HF in ACHD patients and can assist physicians in providing more accurate risk stratification and consider timely advanced therapies and interventional options to patients with various types of congenital lesions.
