Direct Link Between Cardiac Failure and Global Cerebral Atrophy in a Young Adult: A Case Report on Reduced Cerebral Artery Blood Flow

Background

Heart failure is a progressive disease associated with adverse cardiovascular events and increased risks of mortality and hospitalization. Patients with heart failure experience several physical and neuropsychological impairments, including depression and cognitive disorders [1]. Reduced cerebral blood flow or hypotension associated with heart failure may cause structural brain damage and neuropsychological disorders [2]. Some studies have reported the occurrence of brain atrophy, especially in patients with heart failure and comorbid type 2 diabetes [3] or hypertension [4]. Neuropsychological disorders have also been observed in patients aged >40 years with heart failure and structural brain damage [5]. This report presents the case of a 21-year-old woman with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy due to reduced cerebral artery blood flow. We also discuss the impact of brain atrophy in this young adult patient with severe heart failure but no risk factors for atherosclerosis.

Case Report

A 21-year-old woman with no history of any childhood illness, no family history of heart or neurodegenerative disease, no pertinent social history including unbalanced nutritional habits or illicit drug or alcohol use, and no history of major head trauma was admitted to our emergency care unit with dyspnea and leg edema (New York Heart Association [NYHA] functional class IV).

On admission, her plasma B-type natriuretic peptide (BNP) level was 1433 pg/mL (<18.4 pg/mL), heart rate was 64 bpm (sinus rhythm), and cardiothoracic ratio was 64%. The patient showed no abnormal laboratory data indicating the presence of any infectious, autoimmune, metabolic, or endocrine disorder. Right side heart catheterization indicated congestive heart failure (pulmonary capillary wedge pressure: 18 mmHg; cardiac index: 2.0 L/min/m2).

After initial treatment with inotropes and diuretics, she received cardioprotective medications including beta-blockers and angiotensin-converting enzyme inhibitors. Transthoracic ultrasound cardiography showed a left ventricular end-diastolic volume index (LVEDVi) of 92 mL/m2 and left ventricular ejection fraction (LVEF) of 36%. Coronary angiography showed no coronary stenosis, and endomyocardial biopsy results were consistent with the diagnosis of idiopathic dilated cardiomyopathy. Dilated cardiomyopathy involves the heart muscle and is characterized by enlargement and dilation of one or both ventricles along with impaired contractility, which is defined as LVEF <40% [6]. The patient was discharged after 1 month (NYHA class III; BNP, 360 pg/mL) with a post-discharge treatment regimen including carvedilol (15 mg/day), enalapril maleate (2.5 mg/day), spironolactone (25 mg/day), and azosemide (30 mg/day).

One year later, her disease status remained as NYHA class III. She was re-hospitalized to assess candidacy for heart transplantation, and her LVEF was 32%. Cardiopulmonary exercise test results showed a peak oxygen uptake of 8.9 mL/min/kg. She was declared a candidate for heart transplantation according to the International Society of Heart and Lung Transplantation Guidelines [7]. Neurologic complications such as cerebral infarction are risk factors that may contribute to poor post-transplantation outcomes. Thus, the patient underwent mandatory cranial magnetic resonance imaging (MRI) to screen for brain diseases, and the results showed severe global brain atrophy. There were no deep and subcortical white matter or periventricular hyperintensities (Figure 1A, 1B).

We evaluated cerebral blood flow using computed tomography (CT) and single-photon emission CT (SPECT) to rule out brain ischemia. The findings revealed reduced blood flow in the whole brain, especially in the bilateral frontal, temporal, and parietal lobes (Figure 1C). However, no plaques were noted in her carotid artery, and carotid ultrasonographic scans showed maximum intima-media thicknesses (IMT) of 0.5 and 0.4 mm in her right and left carotid arteries, respectively (mean IMT is 0.44 mm at age <39 years in Japanese patients).

Her neuropsychological and neurological findings showed a Mini-Mental State Examination score of 19/30. The Wechsler Adult Intelligence Scale (WAIS)-III scores were as follows (where a score ≤69 is considered extremely low): verbal intelligence quotient (VIQ), 55; performance IQ (PIQ), 49; full IQ (FIQ), 48; verbal comprehension index, 59; working memory index, 50; perceptual organization index, 54; and processing speed index, 54. No discrepancies were noted among these 4 indices, indicating that all domains of her cognitive functioning had reduced equally. Her global cognitive deficits were indicative of mild-to-moderate neuropsychological disability. PCR-based genetic analysis revealed no intellectual disability-causing disease (such as mitochondrial disease) and no Huntington’s disease (4q16.3 HTT gene) or Turner syndrome, as tested by fluorescent in situ hybridization.

Five years after discharge, the patient’s treatment was changed to carvedilol (10 mg/day). The followup ultrasound cardiography data indicated dilated cardiomyopathy progression, with an LVEDVi of 95 mL/m2 and LVEF of 23%. The cerebral blood flow in the cranial occipital lobe had reduced without any indication of atherosclerosis in the brain vessels. Brain atrophy had progressed significantly (Figure 1D–1F). The results of the WAIS-III remained unchanged (VIQ: 57, PIQ: 54, and FIQ: 50).

Discussion

We report the case of a young adult patient with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy who showed reduced cerebral artery blood flow and cognitive impairment.

Cognitive decline is an important contributor to disability in patients with chronic heart failure, affecting 25–50% of patients [8]. In previous reports, middle-aged patients with severe heart failure showed brain atrophy [9]; however, these patients had atherosclerosis as a risk factor. Therefore, it was unclear whether heart failure caused the brain atrophy. Our patient did not have risk factors for atherosclerosis. There were no lacunar or cortical infarcts in her deep and subcortical white matter and there were no periventricular hyperintensities.

Cerebral hypoperfusion and the resulting brain ischemia are the most significant contributors to encephalopathy in patients with heart failure [10]. The augmentation of several cardiovascular risk factors leads to reduced cerebrovascular circulation in middle-aged patients with heart failure. In the Coronary Artery Disease Risk Development in Young Adults (CARDIA) study, early left ventricular dysfunction, as assessed by decreased radial deformation, was found to be associated with reduced gray matter cerebral blood flow, and a trend toward decreased longitudinal deformation was noted [11]. In our patient, the SPECT/CT scans indicated a global reduction in cerebrovascular circulation. Several experimental studies in heart failure models suggest that transverse aortic constriction or myocardial infarction reduces cerebral blood flow and induces cerebral inflammation responses [12]. However, whether long-term reduced cerebral blood flow leads to neurodegeneration and neurological/neuropsychological disorder remains unclear.

The most common cause of cognitive impairment in patients with heart failure is cardio-embolic stroke, with low cardiac output being another possible cause. The reduced blood flow to the brain and cervico-cephalic arteries leads to decreased cerebral perfusion. Therefore, the various etiological subgroups of heart failure should be carefully considered, in combination with brain imaging studies and extensive neuropsychological tests, to determine the profile of cognitive impairment in patients with heart failure [13].

Our patient was diagnosed with increased brain dysfunction and low intelligence. Generally, severe deep white matter lesions indicate potential links to major depression and cognitive disorders [14]. However, brain MRI scans did not show such lesions in our patient. Thus, heart failure was not the leading cause of her mental disability. However, reduction in blood flow to the brain might have partially caused cognitive dysfunction.

We concluded that the low output in our patient with severe heart failure caused reduced cerebral blood flow for a prolonged period, resulting in brain atrophy. This might have been partially responsible for her cognitive dysfunction. However, this hypothesis should be confirmed by re-evaluating the patient’s brain atrophy over a longer period.

Brain atrophy has been observed in middle-aged patients with heart failure who experienced both physical and mental impairments. However, brain atrophy and mortality in young patients with severe heart failure have not been studied adequately. Thus, further investigation into the relationship between brain atrophy and mortality in patients with severe heart failure is warranted.

A limitation of our report is that we did not compare the brain atrophy seen in this patient with brain imaging in other patients with cardiac failure. Consequently, we plan to conduct an observational cohort study to investigate the relationship between brain atrophy and mortality in young patients with heart failure.

Conclusions

In this report, a young adult patient with idiopathic dilated cardiomyopathy, cardiac failure, and global cerebral atrophy showed reduced cerebral artery blood flow and cognitive impairment. Low cardiac output may directly cause brain atrophy in patients with systolic heart failure.