Information about a real patient is presented in stages (boldface type) to expert
clinicians (Drs Uriel
and Sayer), who respond to the information and share their reasoning with the reader
(regular type). A discussion by the authors follows.
The global pandemic caused by coronavirus disease 2019 (COVID-19) has affected more
than 880 000 people in over 180 countries or regions worldwide.
1
COVID-19 is the clinical manifestation of infection with severe acute respiratory
syndrome coronavirus-2 (SARS-CoV-2) and most frequently presents with respiratory
symptoms that can progress to pneumonia and, in severe cases, acute respiratory distress
syndrome and shock. However, there is increasing awareness of the cardiovascular manifestations
of COVID-19 disease and the adverse impact that cardiovascular involvement has on
prognosis.
2
Discriminating between a cardiac or respiratory etiology of symptoms can be challenging
since each may present predominantly with dyspnea. It is also critical to recognize
when cardiac and pulmonary involvement coexist. In this paper, we present 4 cases
that illustrate a variety of cardiovascular presentations of COVID-19 infection. In
addition to discussing the basic clinical physiology, we also discuss clinical decision
making in the current environment, while considering resource allocation and the welfare
of healthcare professionals.
Case 1: Chest Pain and ST Elevation
Patient Presentation
A 64-year-old woman with a history of hypertension and hyperlipidemia and no known
exposure to SARS-CoV-2 presented with persistent chest pressure for 2 days. She denied
dyspnea, cough, fever, chills, diarrhea, recent travel, or sick contacts. On admission,
she was afebrile (37.1°C), her blood pressure was 130/80 mm Hg, heart rate 98 bpm,
and oxygen saturation 100% on 2 L of oxygen. The initial ECG showed sinus tachycardia
at 102 bpm, low voltage QRS complexes in the limb leads, ST segment elevations in
leads I, II, aVL, V2–V6, and PR elevation and ST depressions in aVR (Figure 1A). Troponin
I on admission was 7.9 ng/mL. She was brought to the cardiac catheterization laboratory
where angiography demonstrated nonobstructive coronary artery disease (Figure 1B).
During the procedure the patient’s blood pressure fell to 72/43 mm Hg. Right heart
catheterization was performed revealing a right atrial pressure of 10 mm Hg, pulmonary
artery pressure of 30/20 mm Hg, pulmonary capillary wedge pressure of 21 mm Hg, and
a Fick cardiac index of 1.0 L·min-1·m-2, confirming the diagnosis of cardiogenic shock.
An intraaortic balloon pump (IABP) was inserted and dobutamine infusion was started
with rapid normalization of blood pressure.
Figure 1.
Chest pain and ST elevation. Initial ECG showed sinus tachycardia, low-voltage QRS
complexes in the limb leads, and diffuse ST elevation in leads I, II, aVL, and leads
V2–V6 (A). Coronary angiogram demonstrated mild disease in the left anterior descending
artery and left circumflex artery and 40% stenosis in the mid-right coronary artery
(B). Chest radiography demonstrated clear lungs (C). Transthoracic echocardiogram
with severe increased left ventricular wall thickness and left ventricular ejection
fraction approximately 30% with trace circumferential pericardial effusion (D).
Chest radiography demonstrated normal heart size and clear lungs (Figure 1C). Transthoracic
echocardiography (TTE) demonstrated a small left ventricular end-diastolic dimension
of 2.9 cm, severe concentric left ventricular hypertrophy, and left ventricular ejection
fraction (LVEF) of 30%, with a dilated, severely hypokinetic right ventricle. No significant
valve lesions or dysfunction were noted. A small circumferential pericardial effusion
was noted (Figure 1D). Laboratory analysis revealed an arterial lactate of 5, ferritin
of 967 μg/L, C-reactive protein of 54 ng/mL, and D-dimer 166 ng/mL (normal). There
was also a small increase in M protein on serum electrophoresis, and the ratio of
kappa to lambda free light chains was 2.15.
The differential diagnosis included myopericarditis and cardiac amyloidosis. SARS-CoV-2
testing was positive. She was started on oral hydroxychloroquine 600 mg every 12 hours
for 1 day followed by 400 mg daily for 4 additional days. On IABP and dobutamine infusion,
her cardiac index and lactate normalized and her end-organ function remained stable.
The troponin-I peaked at 18.6 ng/mL and subsequently trended down to 0.4 ng/mL. The
IABP was weaned after 7 days and the patient remained hemodynamically stable off IABP
and inotropes. On repeat echocardiography on hospital day 10, LVEF improved to 50%
and wall thickness was reduced.
Discussion
Dr Uriel: The predominant presenting symptoms of this patient were cardiac in nature
without symptoms suggestive of infection. Thus, although the initial ECG findings
of diffuse ST elevations and elevated cardiac enzymes raised the possibility of myopericarditis,
the typical diagnostic algorithm for acute coronary syndrome was followed, since this
remains a more common cause of this presentation.
As experience with the COVID-19 pandemic grows, the treatment pathway for cardiac
presentations may also evolve rapidly. One area of uncertainty is whether to proceed
to coronary angiography in response to ECG changes and positive troponin, which risks
exposing additional healthcare personnel to infection.
3
Likewise, the role of endomyocardial biopsy to detect myocarditis is uncertain. In
this case, hemodynamic assessment played a crucial role in the detection of profound
cardiogenic shock, guiding appropriate management to achieve a successful outcome.
To reduce the potential contamination associated with patient transport to the catheterization
suite, bedside placement of a pulmonary artery catheter and IABP may be considered
when coronary angiography is not required. Other potential indicators of the hemodynamic
status may include sampling the central venous saturation or hemodynamic assessment
via echocardiography. Whether the increased wall thickness present in this patient
will be characteristic of myocarditis-like presentations with COVID-19 will need further
study. A low threshold to assess for shock in acute systolic heart failure associated
with COVID is important. Likewise, there should be a low threshold for SARS-CoV-2
testing in patients presenting with signs of myopericarditis even in the absence of
fever and respiratory symptoms. Although the patient in this case improved in the
short term, the long-term effects of the myocardial injury are still to be determined.
Case 2: Cardiogenic Shock Rescued by Veno-Arterial-Venous Extracorporeal Membrane
Oxygenation
Patient Presentation
A 38-year-old man with a history of type 2 diabetes mellitus presented with 1 week
of cough, pleuritic chest pain, and progressive shortness of breath to an outside
hospital. On presentation, he was tachypneic with an oxygen saturation of 93% on room
air. Initial labs were notable for a white blood cell count of 9000 per μL with 11%
band forms, 11% lymphocytes, a venous lactate of 1.7 mmol/L, and normal renal and
liver function. The chest radiograph showed bilateral pulmonary opacities. Testing
for SARS-CoV-2 was positive.
Over the course of the next 6 hours, his respiratory status rapidly deteriorated,
requiring intubation for hypoxemic respiratory failure. TTE demonstrated normal left
ventricular function. He developed a supraventricular tachycardia with a rate >200
bpm and was successfully cardioverted. Despite deep sedation and paralysis, the arterial
blood gas revealed pH 7.26, Pco
2 40 mm Hg, and Po
2 56 mm Hg on 100% fraction of inspired oxygen and positive end-expiratory pressure
of 16 mm Hg.
Our mobile extracorporeal membrane oxygenation (ECMO) team was rapidly dispatched.
Before ECMO cannulation, the patient had a bradycardic arrest lasting 6 minutes. He
was cannulated for venovenous (VV) ECMO with a left femoral 25F drainage cannula and
left internal jugular 20F reinfusion cannula. After initiation of VV ECMO, his oxygenation
was acceptable but he became hypotensive, requiring vasopressors. On arrival at our
institution, his blood pressure was 85/70 mm Hg and laboratory analysis showed an
arterial lactate of 5.1 mmol/L, C-reactive protein >300 mg/L, ferritin 4420 ng/mL,
and interleukin-6 of 331.8 pg/mL. The chest radiograph showed diffuse ill-defined
airspace opacities bilaterally (Figure 2A). He was started on hydroxychloroquine (same
dosing protocol as Case 1).
Figure 2.
Cardiogenic shock rescued by veno-arterial-venous extracorporeal membrane oxygenation.
Chest radiograph showed diffuse ill-defined airspace opacities bilaterally (A). Initial
ECG (top) demonstrated sinus tachycardia with incomplete right bundle-branch block.
Repeat ECG (bottom) demonstrated accelerated idioventricular rhythm (B). Transthoracic
echocardiogram demonstrated left ventricular end-diastolic diameter of 4.5 cm, left
ventricular ejection fraction 20% to 25%, with akinesis of mid-left ventricular segments
(C).
Over the next 12 hours, the patient had a persistently elevated lactate, ongoing pressor
requirement and declining urine output. ECG showed low limb lead voltage, sinus tachycardia
and he was noted to have runs of an accelerated idioventricular rhythm (Figure 2B).
TTE showed left ventricular end-diastolic dimension of 4.5 cm, LVEF 20% to 25%, with
akinesis of the mid–left ventricular segments, and normal right ventricular size with
mildly reduced function (Figure 2C). High sensitivity troponin T was 1341 ng/L. After
a multidisciplinary discussion, a 15F arterial limb was added via the right femoral
artery to convert the circuit to veno-arterial-venous ECMO, achieving 2 L of arterial
flow. Systemic heparin was maintained with a goal activated partial thromboplastin
time of 45 to 60 seconds. Over the next 24 hours, the pressor requirement decreased
and the lactate normalized. The patient was decannulated from ECMO after 7 days and
is hemodynamically stable, although he remains on mechanical ventilation.
Discussion
Dr Sayer: The initial presentation of this case was more characteristic of severe
COVID-19 disease than Case 1. Acute respiratory distress syndrome with profound hypoxia
necessitated treatment with VV ECMO. The cardiac involvement only became evident after
the initiation of VV ECMO. The etiology of cardiac dysfunction in this case may be
multifactorial. Direct cardiac injury may occur as the result of viral invasion, while
the cytokine storm induced by COVID-19 may also have toxic effects on the myocardium.
4
In this case, myocardial stunning after cardiac arrest or stress cardiomyopathy are
other potential explanations for the severe left ventricular dysfunction. This case
highlights the need for a multidisciplinary approach to these patients with frequent
reassessment of response to mechanical circulatory support. Reports of ECMO use in
COVID-19 patients are limited, and the outcomes are unknown. Even if ECMO shows clinical
utility, it will play a limited role overall in the current pandemic because of the
extensive resources required to provide the therapy and the limited availability of
those resources.
5
In this case, 2 L/min of blood flow support was sufficient to maintain hemodynamic
stability until the inflammatory response subsided. It will be of interest to see
if such relatively low levels of hemodynamic support are sufficient in other cases
with COVID-19 related cardiogenic shock. A benefit of supporting patients with relatively
low arterial flow rates is a decreased likelihood of left ventricular distention with
its associated consequences.
Case 3: Decompensated Heart Failure
Patient Presentation
A 64-year-old woman with a nonischemic cardiomyopathy (recent normalization of LVEF),
atrial fibrillation, hypertension, and diabetes mellitus presented with a nonproductive
cough and shortness of breath for 2 days. On arrival, she was afebrile, with blood
pressure 153/120 mm Hg, heart rate 100 bpm, and oxygen saturation 88%. Chest radiography
revealed bibasilar predominant patchy airspace opacities, pulmonary vascular congestion,
and small bilateral pleural effusions (Figure 3A). ECG showed sinus rhythm, an isolated
premature ventricular complex, premature atrial complexes, lateral T wave inversions,
and QTc 528 ms (Figure 3B). Laboratory analysis revealed white blood cell 6100 per
μL, serum creatinine 1.11 mg/dL, asparatate aminotransferase 527 U/L, alanine aminotransferase
232 U/L, N-terminal pro B-type natriuretic peptide 6137 pg/mL, high-sensitivity troponin
T 42 ng/mL, C-reactive protein 19.4 mg/L, ferritin 639 ng/mL, and interleukin-6 12
pg/mL. Testing for SARS-CoV-2 was positive.
Figure 3.
Decompensated heart failure. Chest radiography shows pulmonary vascular congestion,
patchy airspace opacities at bases, and bilateral pleural effusions (A). ECG shows
sinus rhythm with premature atrial and ventricular complexes, lateral T-wave inversions,
and a prolonged QT interval (B). Telemetry strip shows prolonged QT interval and torsades
de pointes after R-on-T phenomenon (C).
She was started on broad spectrum antibiotics for management of pneumonia, including
intravenous azithromycin, but hydroxychloroquine was withheld because of the prolonged
QT. Her heart failure was treated with intravenous furosemide and intravenous nitroglycerine.
Her respiratory status worsened rapidly, requiring intubation. She developed hypotension
and was started on vasopressors. An arterial lactate was 6.7 mmol/L. A bedside TTE
showed severely reduced left ventricular function. She was ventilated with a low tidal
volume strategy. Bedside pulmonary artery catheterization revealed a right atrial
pressure of 10 mm Hg, pulmonary artery pressure 45/20 mm Hg, with a Fick cardiac index
of 1.7 L·min-1·m-2. Dobutamine was started but was discontinued when she developed
polymorphic ventricular tachycardia requiring cardioversion (Figure 3C). IABP was
considered but deferred because of improvement in the arterial lactate and blood pressure.
Troponin levels remained relatively stable throughout (peak 214 ng/mL). She remains
intubated on day 9 of her hospitalization because of agitation with ventilator weaning
attempts.
Discussion
Dr Uriel: In this case, a patient with underlying cardiac disease developed profound
decompensation in the context of COVID-19 infection, characterized by a recurrence
of a reduced LVEF accompanied by cardiogenic shock and proclivity for tachyarrhythmias.
Neither myocarditis nor cytokine storm were probable mediators of the recurrence of
her depressed cardiac function, given the relatively low biomarker levels. Whether
patients with recovered systolic function will be at similar risk for this recrudescence
of reduced LVEF awaits further study. Because of tachyarrhythmias, management of the
cardiogenic component of her shock with inotropic agents was not feasible. However,
early intubation and reversal of her respiratory failure led to improvements in hemodynamics
in the absence of direct cardiac support. This case also highlights the need for rapid
correction of hypoxemia in patients with an underlying heart failure, and the usefulness
of pulmonary artery catheterization when shock is thought to be multifactorial. In
patients with a coexisting cardiomyopathy, baseline QT prolongation may impact consideration
of use of hydroxychloroquine and azithromycin.
Case 4: Heart Transplant Recipient
Patient Presentation
A 51-year-old man with a history of heart transplantation in 2007 and renal transplantation
in 2010 presented with intermittent fever, dry cough, and shortness of breath for
9 days. He denied any recent travel or sick contacts. His outpatient immunosuppression
included tacrolimus 5 mg twice daily, mycophenolate mofetil 250 mg twice daily, and
prednisone 5 mg daily.
He was afebrile with a heart rate of 84 bpm, blood pressure of 137/84 mm Hg, and oxygen
saturation of 97% on room air. His chest radiograph was notable for multifocal bilateral
patchy airspace opacities (Figure 4A). The ECG demonstrated normal sinus rhythm with
new nonspecific T-wave inversions in the inferior and lateral leads (Figure 4B). Laboratory
analysis revealed white blood cell 2750 per μL with lymphopenia and a serum creatinine
4.3 mg/dL. Other notable labs included ferritin 1514 ng/mL, C-reactive protein 129.27
mg/L, interleukin-6 120 pg/mL, D-dimer 1.03 µg/mL, N-terminal pro B-type natriuretic
peptide 3212 pg/mL, and high-sensitivity troponin T 16 ng/L. Testing for SARS-COV-2
was positive.
Figure 4.
Heart transplant recipient. Chest radiography with multifocal bilateral patchy airspace
opacities (A). ECG with normal sinus rhythm with new nonspecific ST changes and T
wave inversions in inferior and lateral leads (B).
Following admission, the mycophenolate mofetil was discontinued. The patient was started
on hydroxychloroquine (same dose as previous cases) and azithromycin 500 mg daily
for treatment of COVID-19. He was also started on ceftriaxone for empirical treatment
of pneumonia. TTE showed normal cardiac allograft function. Through the first 5 days
of the hospitalization, the patient was intermittently febrile and his inflammatory
markers remained persistently elevated, though he remained clinically stable. He was
discharged home after 7 days in the hospital.
Discussion
Dr Sayer: The COVID-19 pandemic presents a unique challenge for solid organ transplant
recipients. The clinical symptoms of the patient described in this case were similar
to what has been described in nonimmunosuppressed patients with COVID-19. Of note,
the patient in this case was more than 2 years posttransplant. At this point, immunosuppression
levels are generally much lower than those used in the first months after a transplant.
Data are limited about how to adjust immunosuppression during COVID-19 infection.
In this case, we stopped the mycophenolate mofetil during the infection, with a plan
to resume it after full recovery. In addition to considerations for transplant recipients,
the COVID-19 pandemic has had an additional impact on how heart transplant programs
manage their patients on the waitlist. Programs must balance the risks of new transplant
recipients contracting COVID-19 during their hospitalization with the risks of waitlist
mortality if transplantation is postponed. Furthermore, COVID-19 may also impact the
donor pool because of diversion of crucial resources and fear of disease transmission
from donors.
Take-Home Message
These cases illustrate the variable presentation of COVID-19 involvement of the cardiovascular
system and highlight evolving considerations for treatment pathways across the spectrum
of patients with preexisting cardiovascular diseases (Figure 5). In patients presenting
with what appears to be a typical cardiac syndrome, COVID-19 infection should be in
the differential during the current pandemic, even in the absence of fever or cough.
One should have a low threshold to assess for cardiogenic shock in the setting of
acute systolic heart failure related to COVID-19. If inotropic support fails in these
patients, we consider IABP as the first line mechanical circulatory support device
because it requires the least maintenance from medical support staff. When patients
on VV ECMO for respiratory support develop superimposed cardiogenic shock, the addition
of an arterial conduit at relatively low blood flow rates may provide the necessary
circulatory support without inducing left ventricular distension. Our experience confirms
that rescue of patients even with profound cardiogenic or mixed shock may be possible
with temporary hemodynamic support at centers with availability of such devices.
Figure 5.
Important messages from each cardiovascular presentation of COVID-19. CCTA indicates
cardiac computed tomographic angiography; COVID-19, corona virus disease 2019; ECMO,
extracorporeal membrane oxygenation; IABP, intraaortic balloon pump; TTE, transthoracic
echocardiogram; VA, veno-arterial; and VV, veno-venous.
COVID-19 infection can cause decompensation of underlying heart failure, and may lead
to mixed shock. Invasive hemodynamic monitoring, if feasible, may be helpful to manage
the cardiac component of shock in such cases. Medications that prolong the QT interval
are being considered for COVID-19 patients and may require closer monitoring in patients
with underlying structural heart disease. Our heart transplant recipient exhibited
similar symptoms of COVID-19 infection as compared to the general population. For
those transplant patients requiring hospitalization, how to alter the antimetabolite
and immunosuppression regimens remains uncertain. Furthermore, the COVID-19 pandemic
creates a challenge for the management of heart failure patients on the heart transplant
waitlist, forcing physicians to balance the risks of delaying transplant with the
risks of donor infection and uncertainty regarding the impact of posttransplant immunosuppression
protocols.
Disclosures
Dr Brodie reports receiving grants from Alung Technologies, and serving on the medical
advisory boards for Alung Technologies, Xenios, Breethe, Baxter, and Hemovent. The
other authors report no conflicts.