Hypertension: An Important but Reversible Cause of Systolic Dysfunction in a Cohort of Pediatric Patients

Abstract

Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. We aimed to describe the presentation and outcomes of pediatric CDHTN and identify clinical features associated with resolution of dysfunction. A single center retrospective cohort study of patients ≤ 21 years with CDHTN from January 2005-September 2020 was performed. Patients with systolic dysfunction without another cause, blood pressure >95^th percentile, and physician judgment that dysfunction was secondary to hypertension were included. Demographics, clinical characteristics, echocardiographic findings, and outcomes were examined using Fisher’s exact and Mann-Whitney U tests. Multiple correspondence analysis was used to explore the relationship of resolution of dysfunction to clinical features. Thirty-four patients were analyzed at a median age of 10.9 (IQR 0.3–16.9) years. Patients were divided into groups <1 year (n=12) and ≥1 year (n=22). Causes of hypertension varied by age, with renovascular disease most common in infants (42%) and medical renal disease most common in older patients (77%). Echocardiography demonstrated mild LV dilation (median LV end diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.4). Most patients (81%) had resolution of dysfunction, particularly infants (92%). One patient died and one patient was listed for heart transplant. None required mechanical circulatory support (MCS). No clinical features were statistically associated with resolution of dysfunction. Hypertension is an important but reversible cause of systolic dysfunction in children. Patients are likely to recover with low mortality and low utilization of MCS or transplantation. Further studies are needed to confirm features associated with resolution of dysfunction.

Introduction

The cardiac effects of hypertension have been well described in adults, classically consisting of concentric left ventricular hypertrophy (LVH), diastolic dysfunction, and preserved ejection fraction [1–6]. In adults, systolic dysfunction is thought to only develop after a second insult occurs, most commonly ischemia secondary to coronary artery disease, leading to myocyte loss and reduced ejection fraction [6]. This entity is sometimes referred to as ‘hypertensive cardiomyopathy’, though this name is controversial due to a lack of intrinsic myocardial disease [7]. Despite an increasing global prevalence of pediatric hypertension, there are very little published data regarding cardiac dysfunction secondary to hypertension (CDHTN) in pediatric patients [8].

Case reports and small cohort studies of neonates have demonstrated a clinical presentation of CDHTN in children that is distinct from adults, specifically that of neonates with hypertension presenting with left ventricular (LV) systolic dysfunction [9–13]. One study described echocardiographic findings in 11 neonates with CDHTN, which included LV systolic dysfunction without chamber dilation, concentric LVH, left atrial dilation, and aortomegaly [10]. This small study and other case reports indicate that treatment of neonatal hypertension appears to lead to significant and rapid improvement in echocardiographic abnormalities and clinical status, although this has not been examined in larger studies [10–13].

Adolescents with essential hypertension may present more similarly to adults with findings of LVH, early diastolic dysfunction, left atrial dilation, and aortic dilation [14–17]. There is also evidence of subclinical changes in systolic function in adolescents with higher blood pressures including lower strain indices and ejection fraction (EF) [18,19]. However, there have been no studies of adolescents with reduced ejection fraction secondary to hypertension. Additionally, there is virtually no data on this diagnosis in other age groups. An improved understanding of the clinical characteristics, echocardiographic findings, and outcomes of CDHTN would enhance practitioner clinical decision making and patient counseling.

The purpose of the present study was to describe the presentation and etiologies of hypertension in pediatric patients of all ages with CDHTN, characterize the echocardiographic findings in this diagnosis, describe the evolution of LV dysfunction and outcomes of patients with CDHTN, and identify clinical features associated with resolution of LV dysfunction.

Materials and Methods

Study Design and Population

A retrospective cohort study was performed which included all patients ≤21 years old with a diagnosis of CDHTN between January 2005 and September 2020 at a single center tertiary care children’s hospital. CDHTN was defined as the presence of LV dysfunction (LVD) (shortening fraction (SF) less than 28% or EF less than 50%, without another medical or surgical cause of cardiac dysfunction), documented blood pressure (BP) greater than the 95th percentile for age and height within 3 months of diagnosis, and physician judgment that dysfunction was secondary to hypertension. The study was reviewed by the Institutional Review Board and granted exemption.

Data Source

Patients were identified by searching the electronic echocardiogram database at our institution for echocardiograms completed during the study period demonstrating systolic dysfunction and relevant diagnosis code or free text (See Supplement 1). Further review of the echocardiogram report was then completed to exclude patients with other causes of dysfunction or who did not meet dysfunction criteria for inclusion. The electronic medical record was then reviewed to confirm documented hypertensive blood pressure, lack of other medical or surgical causes of dysfunction, and physician judgement of underlying etiology of dysfunction. An internal database of patients seen in a specialty hypertension clinic at our institution was also queried to ensure inclusion of all eligible patients.

Data Collection

Patient medical records were reviewed for demographics, clinical characteristics, and echocardiographic findings. Clinical characteristics included underlying etiology of the hypertension, duration of hypertension, age at presentation, comorbid medical conditions, symptoms at presentation, current medications, and peak systolic and diastolic blood pressure at presentation. Echocardiographic findings collected were measurements of LV systolic function including ejection fraction, shortening fraction and reading cardiologist’s assessment of qualitative systolic function, LV mass index and z-score, reading cardiologist’s qualitative assessment of LV hypertrophy, LV dimensions including LV end-diastolic dimension z-score, LV end-systolic dimension z-score, interventricular septal dimension z-score, LV posterior wall dimension z-score and presence of diastolic dysfunction. Presence of diastolic dysfunction was defined by the reading cardiologist using any combination of mitral inflow doppler, pulmonary vein flow doppler or tissue Doppler imaging. Given the episodic nature of hypertension, time to blood pressure control was defined as the number of days after diagnosis that there was documentation of a blood pressure less than the 90th percentile and a provider decision not to increase the antihypertensive regimen.

Outcomes

The primary outcomes were resolution of systolic dysfunction defined as EF≥50% or SF≥28% during the study period and at the time of last follow up. Secondary outcomes were recurrence of LV dysfunction defined as having had resolution of systolic dysfunction during follow up period with later worsening of EF to <50% or SF to <28%, clinical status at last follow up, blood pressure percentile at last follow up, qualitative LV function at last follow up, LV EF at last follow up, and LV SF at last follow up.

Statistical Analysis

Descriptive statistics were performed using count with percentage for categorical variables and median with interquartile range (IQR) for continuous variables. Patients without follow up beyond initial presenting echocardiogram were excluded from the outcomes analysis. Statistical differences by age and LVD resolution status were assessed using Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. The relationship between blood pressure control and LVD resolution status was assessed by plotting the medians of peak systolic and diastolic BP percentiles and comparing the two groups using the Mann-Whitney U test. A post hoc sensitivity analysis was also performed excluding patients who experienced recurrence of LV dysfunction during the follow-up. To explore the relationship of resolution of LV dysfunction to multiple clinical features, a multiple correspondence analysis (MCA) was performed.

Results

Cohort Characteristics

A total of 34 patients met inclusion criteria. Characteristics of the cohort at presentation are described in Table 1. The median patient age was 10.9 (IQR 0.3–16.9) years. There was a bimodal age distribution, so patients were divided into infants (<1 year, n=12) and older children (≥1 year, n=22) at the time of diagnosis of CDHTN. Patients typically presented with blood pressure at the 99^th percentile and most were symptomatic (n=21, 62%) at diagnosis. The most common symptoms at presentation were dyspnea, exercise/activity intolerance, fatigue, poor appetite, emesis, and cough. Duration of hypertension was known in 9 of the patients in the ≥1 year group. The median duration of hypertension in these patients was 6 (IQR 4.5–7.0) years. Most patients (n=28, 82%) were admitted at presentation, including all infants. Inotropic medications, most commonly milrinone, were used in a minority of older children (n=7, 32%) but most infants (n=8, 67%). Most patients had at least one underlying comorbidity, most commonly prematurity (n=6, 50%) in the infants and chronic kidney disease (n=13, 59%) in the older children. Obesity was present in 6 patients (27%) within the older cohort.

Table 1.

Baseline characteristics of patients by age group at presentation

Characteristics	Overall n = 34	Age < 1 year n = 12	Age ≥ 1 year n = 22	p-value
Age, years	10.9 (0.3, 16.9)	0.2 (0.0, 0.3)	16.5 (11.6, 17.1)
Sex				0.80
Female	16 (47%)	6 (50%)	10 (45%)
Male	18 (53%)	6 (50%)	12 (55%)
Race				0.001
White	10 (29%)	8 (67%)	2 (9%)
Black	17 (50%)	2 (17%)	15 (68%)
Other	7 (21%)	2 (17%)	5 (23%)
Hispanic ethnicity	7 (21%)	2 (17%)	5 (23%)	>0.90
BMI percentile1	70 (35, 98)	NA	70 (35, 98)
Etiology of hypertension				0.004
Renal	20 (59%)	3 (25%)	17 (77%)
Renovascular	6 (18%)	5 (42%)	1 (4.5%)
Essential/Idiopathic	5 (14.7)	2 (17%)	3 (14%)
Medication side effect	1 (2.9%)	1 (8.3%)	0 (0%)
Other or multiple	2 (5.9%)	1 (8.3%)	1 (4.5%)
SBP percentile	99 (99, 99)	99 (99, 99)	99 (99, 99)	0.20
DBP percentile	99 (98, 99)	99 (98, 99)	99 (98, 99)	0.60
Symptomatic at diagnosis	21 (62%)	9 (75%)	12 (55%)	0.41
Admitted at presentation	28 (82%)	12 (100%)	16 (73%)	0.069
Intubated at presentation	9 (26%)	7 (58%)	2 (9.1%)	0.004
Inotrope at presentation	15 (44%)	8 (67%)	7 (32%)	0.075
BNP	1,203 (492, 4978)	2,838 (695, 19608)	776 (76, 2916)	0.17
Unknown	17
Any comorbidity	30 (88%)	9 (75%)	21 (95%)	0.12
Obesity	6 (18%)	0 (0%)	6 (27%)	0.069
Chronic kidney disease	14 (41%)	1 (8.3%)	13 (59%)	0.009
Prematurity	8 (24%)	6 (50%)	2 (9.1%)	0.013
Chronic lung disease	2 (5.9%)	2 (17%)	0 (0%)	0.12
Other comorbidities	21 (62%)	5 (42%)	16 (73%)	0.14

Categorical variables are summarized as count and percentage. Continuous variables are summarized as median and interquartile range.

¹BMI was not calculated for patients under two years of age (n=13). Fisher’s exact test was performed for categorical variable and the Mann-Whitney U test was used for continuous variable, respectively.

Etiology of Hypertension

The underlying cause of hypertension varied by age group (p=0.004). In patients less than 1 year of age, the predominant cause was renovascular disease (n=5, 42%), including renal artery stenosis and renal artery thrombosis. In patients greater than 1 year of age, the predominant cause was medical renal disease (n=17, 77%), including glomerulonephritis, glomerulosclerosis, polycystic kidney disease, and renal dysplasia. The duration of medical renal disease was known in 8 of these patients with a median of 11.5 (IQR 5–17) years. The remaining patients were diagnosed with medical renal disease at the time of presentation with CDHTN.

Echocardiographic Findings at Presentation

The echocardiographic findings of the cohort at presentation of CDHTN are summarized in Table 2. The median EF at presentation was 46% (IQR 36–49%). At presentation, there was mild LV dilation (median LV end diastolic z-score 2.6, IQR 0.9–3.2) with slightly more dilation in the infants (median LV end diastolic z-score 2.9, IQR 2.6–3.3), though this did not reach statistical significance (p=0.14). Qualitatively, 71% of the cohort had dilation at presentation, including 92% of infants. There was also a suggestion of mild LV hypertrophy (median LV mass z-score 2.4, median LV mass index 79 g/m^2.7), although the median interventricular septal dimension and LV posterior wall dimension z-scores were normal and only 32% of patients had qualitative hypertrophy. A minority of patients (n=5, 15%) had documented diastolic dysfunction. Aortic measurements were not performed in most patients at presentation.

Table 2.

Echocardiographic findings by age group at presentation and during follow-up

Characteristic	Overall n = 34	Age < 1 year n = 12	Age ≥ 1 year n = 22	p-value
Baseline Echocardiogram
LV ejection fraction %	46 (36, 49)	41 (34, 48)	47 (37, 49)	0.46
LV shortening fraction %	22 (15, 26)	19 (14, 22)	23 (18, 26)	0.070
LV end-diastolic dimension z-score	2.6 (0.9, 3.2)	2.9 (2.6, 3.3)	2.1 (0.5, 3.0)	0.14
LV end-systolic dimension z-score	4.3 (2.8, 5.6)	5.6 (4.4, 6.6)	3.8 (2.0, 5.1)	0.021
Interventricular septal dimension z-score	0.9 (0.0, 1.8)	0.6 (-0.3, 1.1)	1.0 (0.1, 2.2)	0.51
LV posterior wall dimension z-score	0.9 (0.3, 2.0)	1.1 (0.7, 1.9)	0.7 (0.0, 1.9)	0.61
LV mass z-score	2.4 (1.4, 3.1)	2.7 (2.2, 3.7)	2.2 (0.9, 3.0)	0.31
LV mass index, g/ht2.7	79 (56, 114)	130 (116, 141)	64 (52, 81)	0.002
Qualitative assessment of LV dysfunction				0.27
Mild	10 (29%)	2 (17%)	8 (36%)
Mild to Moderate	4 (12%)	1 (8.3%)	3 (14%)
Moderate	8 (24%)	2 (17%)	6 (27%)
Moderate to Severe	3 (8.8%)	1 (8.3%)	2 (9.1%)
Severe	9 (26%)	6 (50%)	3 (14%)
Qualitative LV hypertrophy				0.25
Hypertrophy	11 (32%)	2 (17%)	9 (41%)
No hypertrophy	23 (68%)	10 (83%)	13 (59%)
Qualitative LV dilation				0.061
Dilation	24 (71%)	11 (92%)	13 (59%)
No dilation	10 (29%)	1 (8.3%)	9 (41%)
Diastolic dysfunction	5 (15%)	2 (17%)	3 (14%)	0.76
Characteristic	Overall n = 32*	Age < 1 year n = 12	Age ≥ 1 year n = 20	p-value
Echocardiogram Findings During Follow-up
Normalization of LV function				0.37
LVD resolved	26 (81%)	11 (92%)	15 (75%)
LVD unresolved	6 (19%)	1 (8.3%)	5 (25%)
If normalized, duration of dysfunction, days	106 (10, 240)	12 (4, 80)	218 (114, 441)	0.003
If normalized, recurrence of dysfunction during follow-up				0.40
No recurrence	18 (69%)	9 (82%)	9 (60%)
Recurrence	8 (31%)	2 (18%)	6 (40%)
Last Echocardiogram
LV ejection fraction	56 (54, 61)	62 (60, 62)	55 (52, 57)	0.010
LV shortening fraction	33 (25, 35)	36 (34, 38)	29 (24, 33)	0.002
Qualitative assessment of LV function				0.049
LVD	10 (31%)	1 (8.3%)	9 (45%)
No LVD	22 (69%)	11 (92%)	11 (55%)

Categorical variables are summarized as count and percentage. Continuous variables are summarized as median and interquartile range. Fisher’s exact test was performed for categorical variable and the Mann-Whitney U test was used for continuous variable, respectively. Specific echocardiographic findings were not available for some patients and the number of missing data were summarized as follows: 10 for LV ejection fraction, 2 for LV shortening fraction, 2 for LV end-diastolic dimension z-score, 4 for LV end-systolic dimension z-score, 9 for interventricular septal dimension z-score, 8 for LV posterior wall dimension z-score, 10 for LV mass z-score, 9 for LV mass/ht2.7, 8 for LV ejection fraction at the last follow-up, and 1 for LV shortening fraction at the last follow-up.

^*There were two patients lost to follow up.

Evolution of Left Ventricular Dysfunction

The status of patients’ LV dysfunction throughout the follow up period is described in Table 2 and demonstrated in a flow chart in Figure 1. There were two patients lost to follow up. The median time between presenting echo and last follow up echo was 692 days (IQR 463–1337 days). A total of 26 patients (81%) had resolution of dysfunction during the follow up period (median duration 106 days, IQR 10–240 days). Of these 26 patients, 8 had recurrence of LV dysfunction in the follow up period. Recurrence of dysfunction occurred at a median of 83 days (IQR 14–167 days), with only one patient having recurrence more than 1 year after resolution.

Fig. 1.

Blood pressure control and status of LV dysfunction at baseline and last follow-up.

The medians of peak systolic and diastolic BP percentiles were plotted by resolution status of LV dysfunction at baseline and at the last follow-up, respectively. A post hoc sensitivity analysis was also performed excluding the 8 patients who experienced recurrence of LV dysfunction during the follow-up. P-values were calculated using Mann-Whitney U test. A flowchart can be seen demonstrating the status of LV dysfunction in the cohort, including the number of patients with resolution of dysfunction at some point in the follow up period (n=26), the number who had recurrence of dysfunction following resolution (n=8), and the resolution status at the last follow-up. *There were two patients lost to follow up.

At last follow up, 69% (22/32) of patients had normal systolic function. The infants tended to have a shorter duration of dysfunction (12 days vs 218 days, p=0.003) and higher measures of systolic function at last follow up (EF 62% vs 55%, p=0.01, SF 36% vs 29%, p=0.002). Of the 9 patients with qualitatively severe dysfunction at presentation, 7 (78%) had resolution of dysfunction during follow up and 6 (67%) had normal function at last follow up. At the time of resolution of systolic dysfunction, patients were on a median of 2 (IQR 1–4) antihypertensive medications, most commonly beta-blockers (54%), ACE inhibitors (50%), and calcium channel blockers (42%).

Clinical Outcomes

Survival was high (n=31, 97%) over 3.5 (IQR 2.2–6.3) years of follow up. Most patients (n=30, 94%), including all infants, were asymptomatic at last follow up. No patients received mechanical circulatory support (MCS). Only one patient was listed for cardiac transplant in the follow up period and this patient remained listed at last follow up. Echocardiogram at last follow up for this patient revealed SF 11% and severe dilation (LV end-diastolic dimension z-score 6.9). The single patient who died during follow up was a 19-year-old female with a failed renal transplant on hemodialysis with heart failure and elevated pulmonary vascular resistance who died following a diagnostic catheterization procedure complicated by pulmonary edema and ultimately bradycardic and hyperkalemic arrest. On last echocardiogram, this patient had an EF of 44%, SF of 22% and a normal LV end-diastolic dimension.

Clinical Features Associated with Resolution of Left Ventricular Dysfunction

The univariate association of each clinical feature with resolution of LVD is displayed in Table 3. There was no significant association between resolution of dysfunction and age group at presentation, age at presentation, qualitative severity of dysfunction at presentation, etiology of hypertension, presence of LV hypertrophy at diagnosis, presence of LV dilation at diagnosis, symptoms at diagnosis or time to blood pressure control.

Table 3.

Clinical features of patients by whether LV dysfunction resolved during follow-up

Characteristics	Overall n = 32	LVD resolved n = 26	LVD unresolved n = 6	p-value
Age group				0.37
Age: < 1 year	12 (38%)	11 (42%)	1 (17%)
Age: ≥ 1 years	20 (62%)	15 (58%)	5 (83%)
Age at presentation, years	10 (0, 17)	8 (0, 17)	13 (4, 16)	0.62
Qualitative assessment of LV dysfunction at presentation1				>0.90
Mild	10 (31%)	8 (31%)	2 (33%)
Mild to moderate or moderate	10 (31%)	8 (31%)	2 (33%)
Greater than moderate	12 (38%)	10 (38%)	2 (33%)
Etiology of hypertension				>0.90
Renal	19 (59%)	15 (58%)	4 (67%)
Renovascular	6 (19%)	5 (19%)	1 (17%)
Others	7 (22%)	6 (23%)	1 (27%)
LV hypertrophy				>0.90
Hypertrophy	9 (28%)	7 (27%)	2 (33%)
No hypertrophy	23 (72%)	19 (73%)	4 (67%)
LV dilation				0.15
Dilation	24 (75%)	21 (81%)	3 (50%)
No dilation	8 (25%)	5 (19%)	3 (50%)
Symptomatic at diagnosis				>0.65
Asymptomatic	12 (38%)	9 (35%)	3 (50%)
Symptomatic	20 (62%)	17 (65%)	3 (50%)
Time to blood pressure control, days	16.5 (5, 69)	17.5 (5.5, 73.5)	4 (1, 17)	0.12

Categorical variables are summarized as count and percentage. Continuous variables are summarized as median and interquartile range. Fisher’s exact test was performed for categorical variable and the Mann-Whitney U test was used for continuous variable, respectively.

¹LV dysfunction at presentation was combined into three groups when performing statistical tests given limited sample size.

Figure 1 demonstrates the median systolic and diastolic blood pressure percentiles of patients at baseline and last follow up, stratified by whether patient dysfunction resolved. Both groups presented with equally severe hypertension with a median peak systolic and diastolic blood pressure in the 99^th percentile at presentation. At last follow up, the median systolic and diastolic BP percentile fell in the normal range for both groups. There was no statistically significant difference between the systolic or diastolic BP percentiles in patients with resolved dysfunction versus those with unresolved dysfunction at last follow up (p=0.82 and p=0.94 respectively). In the sensitivity analysis performed where patients who had recurrence of their dysfunction were excluded, there was again no statistically significant difference between BP percentiles in the two groups (p=0.79 and p=0.74).

Given the limited sample size, multiple correspondence analysis was performed to evaluate associations of multiple clinical features with resolution of dysfunction (Figure 2). Points which belong to distinct clinical variables that are close together in the same quadrants along the similar direction from centroid would be indicative of possible association. Notably, lack of dilation, renal hypertension and age greater than or equal to 1 year at presentation appeared to be related to persistence of LV dysfunction.

Fig. 2.

The relationship of whether LV dysfunction resolved during follow up to multiple clinical features: multiple correspondence analysis

Interpretation of MCA is based on the proximities between points. Points (belonging to distinct variables) close together in the same quadrants along the similar direction from centroid would be indicative of possible association. The squared cosine (cos2) measures the degree of association between variable categories and a particular axis, indicating the quality of the representation. In this study, the total variance explanation by the MCA is 47.2% (19.5% + 27.7%). To increase the percentage of variance explanation by the MCA, the seven etiology categories were combined into renal, renovascular, and other hypertensions. Levels of LV dysfunction at presentation was also collapsed into three groups: mild, mild to moderate or moderate, greater than moderate.

Discussion

Hypertension is an important cause of systolic dysfunction that has a bimodal age distribution in children. This study retrospectively examined a cohort of pediatric patients with CDHTN over a nearly 16-year period at a single institution. Patients were typically symptomatic at diagnosis, admitted at presentation, and had at least one comorbidity. Underlying etiology of hypertension varied with patient age, with renovascular causes being most common in infants and medical renal causes being most common in older children. Echocardiographic findings were notable for mild LV dilation, particularly in infants, and mild LVH. Mortality within this patient population is very low and a high percentage of patients will have resolution of systolic dysfunction, particularly those under 1 year of age at the time of diagnosis.

Our findings of rapid improvement in both systolic function and clinical status in infants is consistent with prior case reports and findings from Peterson et al. [9–13]. Our finding of mild LVH in the cohort was also consistent with results from Peterson et al. Our results did differ in that our cohort had mild ventricular dilation and a higher median EF (46% compared to 35%). The differences in the findings may be attributable to differences in cohort characteristics, as the Peterson cohort included only patients 0 to 28 days of age and our cohort included pediatric patients of all ages.

Our study focused on ejection fraction and shortening fraction to define systolic dysfunction, which are inherently load-dependent measures [20]. Therefore, control of blood pressure alone would decrease afterload and would be expected to improve these measures in a patient with normal myocardial contractility. Our finding that the median blood pressure on last follow up was normal even in the group of patients without resolution of dysfunction indicates that these patients likely have a true underlying disorder of contractility. Some echocardiography laboratories utilize the velocity of fiber shortening to end-systolic wall stress relationship to assess myocardial contractility, though this is not typically done at our institution and there are some limitations to the use of this measure [20,21]. We attempted to identify clinical features which would predict resolution of dysfunction and did not find any statistically significant predictors, despite blood pressure control at last follow up in both groups. Notably, time to blood pressure control was also not associated with of resolution of dysfunction and was actually longer in patients with resolution of dysfunction. This may be due to small sample size or because physician blood pressure goals are not blinded to patient echocardiographic results, and thus a patient with improved but not normalized blood pressure who has had normalization of cardiac dysfunction by echocardiogram may receive less aggressive blood pressure management. Our study is unique in that to our knowledge it represents the largest cohort of patients with CDHTN ever studied and represents the only study of pediatric patients with CDHTN in all age groups. The results of our study draw attention to the clinical characteristics of this clinical entity, identification of which by practitioners has important implications for patient treatment and prognosis as compared to other causes of systolic dysfunction. Our results will also aid practitioners in providing appropriate counseling to families regarding the expected course of this disease process.

Limitations

There are several limitations to our study which should be noted. It is a single center study at a large tertiary care children’s hospital and thus results may not be generalizable to other care settings. Further, the rarity of the diagnosis limited our sample size which limited our power to identify clinical features associated with resolution of LV dysfunction. Future studies with a larger sample size would allow for greater power to detect significant risk factors for resolution of dysfunction as well as perform multivariable analysis. Additional limitations are secondary to the retrospective nature of our study. This includes ascertainment bias in the form of more frequent screening echocardiograms performed in specific patient populations with hypertension and inability to assess certain echocardiographic findings such as aortomegaly due to missingness in most subjects since aortic dimensions are not routinely measured as part of our institution’s ventricular function protocol. Finally, there is no diagnosis code or agreed upon definition of cardiac dysfunction secondary to hypertension. This study focused on patients with systolic dysfunction, but there may be an additional subset of patients with isolated diastolic dysfunction secondary to hypertension which were not included.

Conclusion

In conclusion, we report the presentation of 34 pediatric patients with CDHTN at our institution over an almost 16-year period, which represents the largest cohort of patients with CDHTN ever studied. There was a bimodal age distribution in our cohort and outcomes were favorable with low mortality and a high proportion of patients with resolution of systolic dysfunction, particularly those under 1 year of age. Identification of hypertension as the cause of cardiac dysfunction is vital, as these patients do not often require mechanical circulatory support or transplantation. Additional studies are needed to confirm factors associated with resolution of dysfunction.

Abbreviations

LVH

Left ventricular hypertrophy

CDHTN

Cardiac dysfunction secondary to hypertension

EF

Ejection fraction

LV

Left ventricular

SF

Shortening fraction

BP

Blood pressure

IQR

Interquartile range

MCA

Multiple correspondence analysis

MCS

Mechanical circulatory support