Abstract
We report a COVID19 case with acute heart and kidney failure in a
healthy young male. Echocardiography showed severe systolic and
diastolic left ventricle dysfunction, with diffuse myocardial
thickening. Cardiac MRI showed aspects of focal myocarditis, and
hypertensive cardiomyopathy. Renal
biopsy demonstrated limited acute tubular injury, and hypertensive
kidney disease. Coronary angiography excluded critical stenoses. Unlike
what we initially suspected, myocardial inflammation had a limited
extent in our patient; severe hypertension causing cardiomyopathy and
multi-organ damage, not diagnosed before, was primarily responsible for
severe illness. Correct diagnosis and guidelines-directed treatment
allowed a favorable course.
BACKGROUND
Coronavirus disease 2019 (COVID-19) is at the moment an international
public health emergency, caused by a novel enveloped RNA
beta-coronavirus, named ‘severe acute respiratory syndrome
coronavirus-2’ (SARS-CoV-2). The infection is mainly characterized by
respiratory tract symptoms, presenting as mild flu-like illness to
potentially lethal acute respiratory distress syndrome or fulminant
pneumonia, but relevant cardiovascular complications and multi-organ
failure can occur in severe cases [1]. Patients with known
cardiovascular disease and risk factors appear more vulnerable to the
infection, and hypertension is highly prevalent in patients who develop
severe illness. Pathological mechanism underlying this association in
still not completely elucidated: binding of the virus to
angiotensin-converting enzyme 2 receptor (ACE-2), highly expressed on
endothelial surfaces, with consequent renin-angiotensin-aldosterone
system deregulation, and cytokine storm seem to have a relevant role
[2].
We report a case of acute HF and documented cardiac inflammation during
COVID-19. Multi-modality cardiac imaging and a challenging
interdisciplinary medical approach lead to a de-novo diagnosis of
hypertensive multi-organ damage, exacerbated by concomitant viral
infection.
CASE PRESENTATION
A 45-years old man presented to our emergency department in April 2020
for atypical chest pain, fever and worsening effort dyspnoea from 7 days
before. His past medical history was unremarkable and he denied alcohol
and/or drugs abuse. On his arrival high blood pressure (BP = 180/110
mmHg), bi-basal pulmonary rales and mild leg swelling were detected;
oxigen saturation was 93% while breathing ambient air.
Electrocardiography showed sinus tachycardia with left axis deviation,
slight diffuse ST depression more prominent in inferior-lateral leads
(Fig. 1A ). Blood tests revealed a significant increase in
Troponin T (82 ng/L; being 14 ng/L the upper reference limit of normal -
URL), serum creatinine (3.1 mg/dl; eGFR 20 ml/min
ml/min/1.73m2) and C-reactive protein (30 mg/L; being
5 mg/L the URL). At blood cell count, neutrophils were slightly
augmented and lymphocytes slightly diminished. Nasopharyngeal swab was
positive for SARS-CoV-2 infection. Chest X-rays and High resolution
computed tomography scan of the lungs showed ground glass-like hyper
density opacities limited to the peripheral portions of inferior lobes
bilaterally, and a small area of consolidation in the left superior lobe
(Figure 1B, 1C ). Transthoracic echocardiography was also
performed and showed mild increase in LV dimension (end diastolic
diameter: 57 mm; end diastolic volume: 141 ml, 83 ml/m2 BSA) and
moderate increase in walls thickness (interventricular septum = 13.5 mm;
posterior wall = 11 mm), with a sparkling appearance. LV ejection
fraction (LVEF) was severely reduced because of a diffuse parietal
hypokinesis (LVEF = 30%; quantified by Simpson’s method). Left atrium
was moderately enlarged (area = 29 cm2), and the
mitral diastolic filling pattern was restrictive. There was a mild
mitral and tricuspid regurgitation and a mild pericardial effusion was
noted behind the inferior-lateral LV wall.
A few hours after admission to our cardiac intensive care unit,
patient’s condition degenerated abruptly; he presented BP elevation to
210/130 mmHg and respiratory failure, requiring nitroglycerin infusion,
high doses of intravenous furosemide and non-invasive ventilatory
support with continuous positive airway pressure (CPAP) of 10 cm H20.
From the next days, clinical conditions began to improve, allowing
removal of CPAP on day 3. Therapy with bisoprolol was initiated and
gradually titrated up to 3.75 mg/die; amlodipine 10 mg/die and
Alfuzosine 2 mg bid were also introduced for BP control. For viral
infection, idroxichloroquine (200 mg bid) and darunavir/ritonavir
(800/100 mg od) were administered for 10 and 5 days respectively
according to local protocol. Feverish episodes (temperature
> 38°C) persisted for the first 4 days. Clinical laboratory
tests trend during hospitalization is summarized in Table 1 .
Notably, serum creatinine remained constantly elevated; there was modest
proteinuria (228 mg/L), without Bence-Jones proteinuria; serum and urine
protein immunofixation excluded monoclonal free light chains.
When patient’s clinical conditions were stable, echocardiogram was
repeated and confirmed diffuse parietal hypokinesis with improvement in
LV systolic and diastolic function (LVEF = 38% and ‘pseudonormal’
diastolic filling pattern) (Figure 2) . Diffuse myocardial
thickening was still evident. 2D Speckle-tracking showed diffuse
reduction of global longitudinal strain, more severe in anterior
segments, and partial apical sparing. Cardiac magnetic resonance imaging
(MRI) was performed, showing increased symmetric and circumferential
wall thickness, with diffuse LV hypokinesis (LVEF 35%) and mild
hypokinesis of right ventricle (RVEF 41%). Short tau inversion recovery
and T2-Mapping sequences demonstrated the presence of focal myocardial
edema, in medium and apical segments of anterior wall and anterior
septum. Phase-sensitive inversion recovery sequences showed a diffuse
and intramural late gadolinium enhancement (LGE) of LV myocardium in all
segments, with circumferential distribution. Pericardial effusion was
not present (Figure 3 ). This pattern resulted appeared
consistent with hypertensive cardiomyopathy, and myocarditis of limited
extent. The day after, the patient underwent cranial computed
tomography, showing multiple ischemic lacunar foci of the basal ganglia
bilaterally, a stabilized ischemic lesion of the right corona radiata
and white matter hypodensity (Supplementary files, figure 1) .
Doppler ultrasound excluded clinically relevant carotid stenosis, and
significant renal arteries pathology. Renal biopsy demonstrated diffuse
acute tubular injury and modest chronic interstitial inflammation, with
minimal tubulitis. Severe arteriolar hyalinosis (also in preglomerular
arterioles), glomerular capsular thickening and capillary basement
membrane wrinkling and duplication were also present, as for chronic
hypertensive kidney disease (figure 4 ). Amyloid deposits were
excluded. Fifteen days after admission, the patient was discharged. One
month later, after clinical and biochemical resolution of COVID-19 as
demonstrated by two consecutive negative nasopharyngeal swabs, he was
readmitted in our Unit for coronary angiography control. This showed
diffuse atherosclerotic disease of epicardial vessels without critical
stenoses (Supplementary files, Figure 2 ). A new echocardiogram
demonstrated further reduction of LV volumes with improvement in EF (to
46%). Renal function was persistently impaired (serum creatinine: 2.9
mg/dl). Cardiac MRI performed 2 month later, showed a reduction in
biventricular volumes with improvement in LVEF up to 50%; LV parietal
hypertrophy was unchanged (septal thickness: 13 mm) with mild, diffuse
intramural LGE; T1 and T2 sequences showed resolution of edema.
DISCUSSION
The present report describes a case of COVID 19 with acute respiratory
failure, acute myocardial and kidney injury, in a patient firstly
diagnosed with severe hypertension causing dilated cardiomyopathy and
multiple target-organ damage. Definite diagnosis was possible through
myocardial and renal tissue characterization. Notably, they were both
obtained in a living patient with severe COVID 19, the first through
cardiac magnetic resonance, the latter by means of kidney biopsy.
Preexisting CV disease were found to be independent predictor of
in-hospital mortality in COVID-19 patients [1,2]. Moreover, severe
illness may be complicated by acute myocardial injury, clinically
expressed by cardiac troponin release, electrocardiographic
abnormalities and myocardial dysfunction [3]. Cardiac involvement
may occur due to ischemic (acute myocardial ischemia/infarction) or
non-ischemic processes, including stress-induced cardiomyopathy and
myocarditis.
Several cases of acute heart failure or cardiogenic shock caused with
echo-documented and MRI-proven myocardial inflammation due to COVID-19
have been published so far [4, 5, 6]; cardiac MRI showed diffuse,
extensive myocardial edema conditioning global cardiac function
impairment. In our case, echocardiography during hospitalization showed
diffuse myocardial thickening, with an echo-bright appearance, severe
diastolic dysfunction with initially restrictive filling pattern,
bi-atrial enlargement and mild pericardial effusion. Moreover, global
longitudinal strain with partial apical sparing was detected at
2D-speckle tracking. These aspects aroused at first the suspect of a
possible infiltrative cardiomyopathy, as amyloidosis. Other diagnostic
hypothesis were: extensive COVID-19 related myocardial inflammation with
diffuse interstitial infiltrates, or misdiagnosed hypertensive
cardiomyopathy. Systemic amyloidosis was also at first suggested by the
presence of kidney failure, but this hypothesis was later rejected on
the basis of serum and urine immunofixation. Cardiac MRI was crucial in
the diagnostic process; it confirmed diffuse myocardial thickening and
systolic impairment; myocardial edema depicted by T1 and T2 sequences
had a limited extent, thus suggesting that the severe cardiac impairment
was not exclusively caused by myocarditis. LGE pattern appeared non
suggestive for amyloidosis and supported the diagnosis of hypertensive
cardiomyopathy. Interestingly, cardiac function gradually improved
during and after hospitalization, in parallel with COVID-19 resolution
and effective treatment of hypertension.
Kidney impairment is frequent in COVID-19 patients: more than 40% of
them have proteinuria at hospital admission [7], while some
critically ill patients may develop during hospitalization an acute
kidney injury (AKI) [8]. The most common pathogenic factors appear
related to direct renal injury (promoted by the binding of SARS-CoV-2 to
ACE-2 on tubular cells and podocytes), to microthrombi formation due to
hypercoagulability, and to the effects of acute systemic inflammatory
response[8]. Kidney biopsy findings in our patient revealed diffuse
acute tubular damage with modest interstitial inflammation, as for AKI,
together with glomerular and vascular alterations consistent with
chronic hypertensive nephropathy. Resolution of infective process
however did not lead to a significant improvement of kidney function,
thus we can speculate that in this patient the long-time undiagnosed
severe hypertension was the main contributor to his kidney impairment.
Cranial CT findings, suggestive for hypertensive encephalopathy, were
also in keeping with a severe uncontrolled hypertension not diagnosed
before.
In conclusion, our report depicts how a condition of severe, untreated
hypertension can increase cardiac vulnerability to COVID-19 infection:
acute inflammatory alterations, even of limited extent, may critically
destabilize a preexisting organ damage of hypertensive etiology, leading
to a condition of severe HF. This report highlights that in these
patients the same mechanistic approach to cardiac and systemic
abnormalities should be used, increasing utilization of multi-modality
imaging and diagnostic tools that may help us to make a correct
diagnosis.