Cardiac Complications of COVID-19 Infection and the Role of Physical Activity : Journal of Cardiopulmonary Rehabilitation and Prevention

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Cardiac Complications of COVID-19 Infection and the Role of Physical Activity

Smer, Aiman MBBCh; Squires, Ray W. PhD; Bonikowske, Amanda R. PhD; Allison, Thomas G. PhD, MPH; Mainville, Rylie N. BS; Williams, Mark A. PhD

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Journal of Cardiopulmonary Rehabilitation and Prevention 43(1):p 8-14, January 2023. | DOI: 10.1097/HCR.0000000000000701
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The first human cases of the novel coronavirus disease-2019 (COVID-19), subsequently named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), were first reported in the city of Wuhan in China in December 2019.1 A cluster of atypical pneumonia cases with a triad of fever, cough, and shortness of breath of unknown etiology linked to a wholesale seafood market in Wuhan were reported to the World Heart Organization on December 31, 2019. Shortly afterward, the virus spread rapidly across the world sparking a global pandemic affecting hundreds of millions of people with >5 million deaths worldwide. The SARS-CoV-2 virus causes COVID-19 infection and is a highly pathogenic single-stranded RNA virus with zoonotic origin; bats are the natural host.2 The virus ability to transmit via aerosol and droplet is responsible for the widespread of COVID-19 infection. Based on current epidemiological data, the virus incubation period is 1-14 d, with most patients no longer contagious 10 d after symptoms onset.3 All ages are susceptible to COVID-19 infection. However, elderly patients with comorbidities, particularly cardiac and pulmonary, are more likely to develop severe illness.4 The presence of underlying cardiovascular disease (such as hypertension and coronary artery disease) is associated with more severe infection and higher mortality.4,5 Infection with COVID-19 can trigger a severe immune response and hypercoagulable state, a combination of inflammation and thrombosis leading to tissue injury, organ damage, and thrombotic events.6,7 The majority of patients with symptomatic COVID-19 present with pulmonary symptoms, but cardiac manifestations are also common (Figure). The clinical cardiac presentations of COVID-19 are highly variable. Some patients are asymptomatic from a cardiac perspective but have abnormal cardiac testing (such as elevated cardiac troponin, asymptomatic arrhythmia, or abnormal cardiac imaging), while other patients present with cardiac symptoms due to myocardial infarction, heart failure (HF), or arrhythmias. COVID-19 can cause primary cardiac involvement manifested with acute myocardial infarction, myocarditis, and arrhythmias as well as secondary (myocardial injury and HF cardiac involvement due to a systemic inflammatory response (Figure).8 In clinical practice, secondary cardiac involvement is more common and usually associated with multiorgan damage.

F1
Figure.:
Summary of cardiac manifestations of COVID-19 infections. Primary involvement includes acute coronary syndromes, myocarditis, and brady- and tachyarrhythmias. Secondary involvement includes acute myocardial injury manifested with elevated cardiac troponin levels above the 99th percentile of upper reference limit. Heart failure and stress cardiomyopathy are also considered secondary complications of COVID-19 infection. This figure is available in color online (www.jcrpjournal.com).

CARDIAC MANIFESTATIONS OF COVID-19

Myocardial injury is one of the earliest and most common cardiac manifestations of COVID-19 infection, which is defined by elevated cardiac troponin level in the absence of clinical evidence of ischemia.9,10 There are several potential mechanisms for COVID-19-induced myocardial injury such as direct viral myocyte injury, microvascular thrombosis, and hypoxia, as well as stress-related and cytokine-mediated cardiomyopathy.11–13 Assessment for any symptoms and signs of ischemia is essential to distinguish myocardial infarction from injury, which requires no specific therapy. However, myocardial injury in patients with COVID-19 has been associated with worse clinical outcomes.14

It is well documented that COVID-19 is a prothrombotic disease and can cause both microvascular and macrovascular coronary thromboses.13,15 In addition, COVID-19 infection can trigger plaque rupture in patients with underlying coronary artery disease.15 The true incidence of acute coronary syndrome in COVID-19 patients remains unclear. However, when compared with pre-pandemic data, national registries reveal decreased hospitalizations for acute coronary syndrome, including ST-segment elevation myocardial infarction (STEMI), by 40-50% during the pandemic.16–19 This significant decline in the number of STEMI admissions may be due to patient concerns regarding hospital safety measures to protect them from COVID-19 infection, access issues, and increased out-of-hospital deaths.20 In clinical practice, there are several challenges to the management of patients with acute coronary syndrome with documented or suspected COVID-19 infection.15,21,22 The first challenge is the uncertainty of the diagnosis of STEMI, as COVID-19 can also cause myocarditis, coronary spasm, and stress cardiomyopathy mimicking STEMI presentation.21 The second major challenge is the concern regarding the safety of health care personnel, which may lead to less diagnostic procedures and delay in therapeutic percutaneous coronary interventions (PCI).15 Although fibrinolytic therapy can be safely used in COVID-19 patients, primary PCI remains the standard of care for STEMI patients when it can be done in a timely manner with the use of personal protection equipment.21,22 On the other hand, early invasive strategy for non-STEMI is only reserved for high-risk patients with refractory angina, HF, arrhythmia, and hemodynamic instability.15 Guideline-directed medical therapy should be administered including antiplatelet agents, β-blockers, nitrates, statins, and heparin therapy.

It is well-known that viral myocarditis is the most common cause of acute myocarditis and COVID-19 is not an exception.23 Several case reports have been published on patients diagnosed with myocarditis who are COVID-19 positive.24–26 In most cases, the diagnosis of acute myocarditis was based on the symptom of chest pain with elevated cardiac troponin and abnormal cardiac testing, either abnormal electrocardiogram, echocardiogram, or preferably cardiac magnetic resonance showing typical findings of diffuse edema with or without pericardial involvement. Stress cardiomyopathy (Takotsubo) has also been associated with COVID-19 infection.27 While acute myocarditis occurs mainly in young patients, stress cardiomyopathy affects primarily older female patients with COVID-19.27 Both conditions can mimic STEMI and create a diagnostic dilemma. The classic apical akinesis with hyperdynamic basal segments on echocardiogram can help reach the correct diagnosis and avoid unnecessary invasive coronary angiography. Management of COVID-19 myocarditis and stress cardiomyopathy should be based on therapy for ventricular dysfunction and arrhythmic risk.

Arrhythmias are a common cardiac manifestation of COVID-19. Patients with COVID-19 are susceptible to both tachy- and bradyarrhythmias.28 Therefore, ECG telemetry is recommended for hospitalized patients with COVID-19. Sinus tachycardia and new-onset atrial fibrillation are the most common rhythm problems in hospitalized patients with COVID-19.28 Rate control strategy is preferred when managing atrial fibrillation, and the use of anticoagulation is recommended regardless of CHA2DS2-Vasc (congestive HF, hypertension, age, diabetes mellitus, stroke or transient ischemic attack, sex, vascular) score due to the increased thrombotic risk with COVID-19 infection.28 The initial use of hydroxychloroquine and azithromycin resulted in QTc interval prolongation and subsequently led to ventricular arrhythmias, particular torsades de pointes.29 In critically ill patients, sinus bradycardia and transient asystole may occur during intubation, tracheal suction, and prone position possibility due to high vagal tone. Treatment of arrhythmias should follow current arrhythmia management guidelines and focus on addressing reversible causes such as hypoxia, electrolyte disturbances, and avoidance of using QTc-prolonging medications.8

COVID-19 can precipitate acute HF through multiple mechanisms related to acute illness, hypoxia, cytokine storm, myocardial ischemia, acute myocarditis, or stress cardiomyopathy.11 Obtaining an echocardiogram is essential to diagnose left ventricular dysfunction, regional wall motion abnormalities, and abnormal filling pressures. Although brain natriuretic peptide is a reliable test for diagnosis of HF, it can be elevated in COVID-19 patients with no clinical evidence of HF.30 Diuretics and guideline-directed medical therapy for left ventricular dysfunction are recommended. In severe cases, some patients develop cardiogenic shock requiring inotropes and the use of veno-arterial extracorporeal membrane oxygenation.31,32

PRE-INFECTION PHYSICAL ACTIVITY, MAXIMAL EXERCISE CAPACITY, AND SEVERITY OF COVID-19 ILLNESS

Persons who are physically inactive before contracting COVID-19 experience far worse outcomes than more active individuals. Sallis and colleagues33 followed 48 440 adults (48 ± 17 yr, 75% <60 yr, 62% women) after administering self-report questionnaires to assess habitual levels of physical activity. Three or more physical activity questionnaires were administered between March 19, 2018, and March 18, 2020, and the diagnosis of COVID-19 was made between January 1, 2020, and October 21, 2020. Subjects were classified into three physical activity groups: inactive (0-10 min/wk, 14% of subjects), some activity (11-149 min/wk, 79% of subjects), and active (≥150 min/wk as recommend by the Centers for Disease Control and Prevention, 6% of subjects). Subjects who subsequently developed COVID-19 and were inactive had increased risk of requiring hospitalization (OR = 2.26: 95% CI, 1.81-2.83), ICU admission (OR = 1.73: 95% CI, 1.18-2.55), and death due to COVID-19 (OR = 2.49: 95% CI, 1.33-4.67) compared with active subjects who became infected. Compared with subjects who performed some physical activity, those who were inactive had a greater risk of hospitalization (OR = 1.20: 95% CI, 1.10-1.32), ICU admission (OR = 1.10: 95% CI, 0.93-1.29), and death due to COVID-19 (OR = 1.32: 95% CI, 1.09-1.60).33

Maximal exercise capacity in metabolic equivalents of task (METs) estimated from graded exercise testing is inversely related to the risk of hospitalization due to COVID-19. Brawner and associates34 studied 1181 adults who underwent graded exercise testing between January 1, 2016, and February 29, 2020, and who later underwent testing for SARS-CoV-2. They identified 246 subjects (59 ± 12 yr, 58% women) who tested positive for the virus. Thirty-two percent (n = 89) required hospitalization. Maximal exercise capacity in metabolic equivalents (METs) was lower among subjects who were hospitalized compared with those not hospitalized (6.7 ± 2.8 METs vs 8.0 ± 2.4 METs, P < .001). Peak METs were inversely associated with the likelihood of hospitalization (adjusted model OR = 0.87: 95% CI, 0.76-0.99).

POST-COVID-19 SYNDROME AND CARDIORESPIRATORY FITNESS AFTER COVID-19 INFECTION

Post-COVID-19 syndrome (PCS), also called long-haul COVID, long COVID, or post-acute sequelae of SARS-CoV-2 infection, is defined as persistent signs and symptoms lasting ≥4 wk after the initial diagnosis. There are no currently accepted diagnostic tests.35 Post-COVID-19 syndrome is a multiorgan/multisystem disease.36 For some patients, symptoms from the initial infection completely resolve and days to weeks later recur (honeymoon period). The most common signs and symptoms include three categories: fatigue and dyspnea; widespread pain; and orthostatic intolerance and tachycardia due to autonomic dysfunction similar to postural orthostatic tachycardia syndrome (POTS).36–38 For the specific diagnosis of PCS, signs and symptoms must exceed what would be explained by tissue damage due to COVID-19, cause a significant decline in baseline function, and include one or more of the following: fatigue with exertional intolerance; dyspnea; persistent joint pain; orthostatic intolerance, dizziness, and persistent or orthostatic tachycardia; impaired concentration or short-term memory (brain fog).

Additional frequent signs and symptoms include anosmia (loss of the sense of smell), dysgeusia (altered perception of taste), anxiety, depression, paresthesia, sleep disturbances, and palpitations.36 Symptoms commonly worsen after physical or mental activity.35 Most symptoms are more common in women than in men and with increasing age.39 Although some patients experience relatively mild forms of PCS, others become debilitated and are not able to return to pre-illness function for several months. Unfortunately, symptoms may persist in approximately 30% of patients with PCS for ≥9 mo.40

Post-COVID-19 syndrome is similar to previously recognized post-infection syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, chronic Epstein-Barr virus, and post-treatment Lyme disease syndrome.35 The incidence of PCS is substantial and concerning. Taquet et al39 evaluated the electronic health records of 273 618 COVID-19 survivors and reported post-PCS symptoms in 37% of patients between 3 and 6 mo after the initial diagnosis. FAIR Health evaluated 1 959 982 COVID-19 patients for PCS symptoms ≥30 days after the initial diagnosis of COVID-19.41 The overall incidence was 23% and was higher in patients with more severe disease. However, PCS also occurred in 19% of initially asymptomatic individuals. The highest incidence was for patients requiring hospitalization for COVID-19 (50%) and was lower for symptomatic patients who did not require hospitalization (28%).41

The potential enormous scope of the problem of PCS is illustrated by data from the Centers for Disease Control and Prevention, accessed November 5, 2021, indicating that there were approximately 46 million COVID-19 survivors in the United States.42 Using an overall incidence of 23% for PCS from the FAIR Health data, there were approximately 10.6 million persons who had experienced the syndrome in the United States as of early November 2021.

CARDIOPULMONARY EXERCISE TESTING IN PATIENTS AFTER COVID-19 INCLUDING THOSE WITH POST-COVID-19 SYNDROME

Arena and colleagues43 recently discussed the potential roles for cardiopulmonary exercise testing (CPX) in patients with viral infections such as COVID-19. They suggested that variables such as peak oxygen uptake (V˙o2peak), V˙E/V˙co2 slope, blood pressure, electrocardiogram, arrhythmias, and heart rate recovery measured during CPX may be helpful in predicting outcomes in patients with viral infections, tracking the recovery process, and determining the need for formal rehabilitation.

Three articles from European centers reported CPX data for a total of 266 patients tested approximately 3 mo after being hospitalized with COVID-19.44–46 It is highly likely that a portion of the patients in these studies had PCS, but the presence of the syndrome was not specified in any of these articles. The majority were men (63%) and average age was approximately 57 yr. Mean V˙o2peak was 26 mL/kg/min, which was 83% of age and sex predicted. Mean V˙E/V˙co2 slope and arterial oxygen saturations were normal. All three articles concluded that the primary reason for below average cardiorespiratory fitness in these individuals was deconditioning.

Barbagelata et al47 reported CPX data from South America for 200 patients (49±14 yr) with COVID-19 (20% required hospitalization) who performed the CPX approximately 80 d after the diagnosis. Post-COVID-19 syndrome was arbitrarily defined as dyspnea and/or fatigue persisting ≥45 d after symptom onset and was present in 112 individuals (59% women). Compared with COVID-19 patients without persistent symptoms, V˙o2peak was 3.0 mL/kg/min lower in patients with persistent symptoms (P = .017). However, percent predicted V˙o2peak was normal for both groups (92.9 vs 89.7%, P = .257). Eighteen patients with persistent dyspnea and/or exercise intolerance after COVID-19 infection (41 yr, 67% women) underwent CPX an average of 37 wk after the diagnosis in the study by Alba and colleagues.48 Median V˙o2peak was 20 (16, 27) mL/kg/min, 86% of predicted, and was not different for age- and sex-matched subjects who performed CPX prior to the pandemic for the assessment of dyspnea. The median V˙E/V˙co2 slope was normal (29.8, 27.4, 32.7).

Mancini and associates49 performed CPX on 41 patients referred for unexplained dyspnea (45 ± 13 yr, 56% women) at an average of 3.3 mo after COVID-19 infection. Nineteen patients (46%) fulfilled diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Mean V˙o2peak was 20.3 ± 7.0 mL/kg/min. Mean V˙E/V˙co2 slope and arterial oxygen saturations were normal. However, 24 patients had evidence of circulatory limitation (V˙o2peak <80% of predicted with a low oxygen pulse and elevated V˙E/Vco2 slope). Thirty-six patients (88%) exhibited ventilatory abnormalities (dysfunctional breathing pattern, elevated V˙E/V˙co2 slope, and hypocapnia at rest).

Singh and colleagues50 reported evidence for impaired oxygen extraction during exercise (peripheral limitation) in 10 patients with persistent exercise intolerance after COVID-19. Patients performed an invasive CPX (with right heart catheterization during exercise) 11 mo after infection. Average V˙o2peak was 70 ± 11% of predicted and mean V˙E/V˙co2 slope was elevated at 35 ± 5. Systemic oxygen extraction at maximal exercise was significantly lower in patients than in healthy controls (0.49 ± 0.1 vs 0.78 ± 0.1, P < .0001). Cardiac index at maximal exercise was normal, consistent with a peripheral limitation during exercise.

We evaluated the responses of 50 consecutive patients from the Post-COVID Care Clinic (PCOCC) at Mayo Clinic in Rochester, Minnesota, who were referred for CPX for objective assessment of aerobic exercise capacity. All patients met the specific diagnostic criteria for PCS presented previously and performed CPX within a few days of the diagnosis. Tests were performed on treadmills with analysis of expired air and measurements of blood pressure and the electrocardiogram as previously described.51 Arterial oxygen saturation was measured with pulse oximetry. Patients were able to exercise, were not a random sample from the PCOCC, and may not be representative of the typical PCS patient.

The subjects included 34 women, mean age was 47 ± 16 yr (range: 18-76 yr), and body mass index was 30.2 ± 6.7 kg/m2 (range: 18-47 kg/m2). Of the 50 subjects, eight required hospitalization for treatment of COVID-19 pneumonia with supplemental oxygen and none received care in an intensive care unit. None of the subjects had a pre-COVID-19 history of cardiovascular diseases and one had a history of chronic obstructive pulmonary disease. Common symptoms, including prevalence, at the time of the PCOCC evaluation are provided in Table 1. At least 70% of subjects reported either fatigue, dyspnea, musculoskeletal pain, or mental fog. Three or more symptoms were endorsed by 88% of the subjects.

Table 1 - Prevalence of Common Post-COVID-19 Symptoms in Patients Referred for Cardiopulmonary Exercise Testing From a Post-COVID-19 Care Clinic (n = 50)
Symptom Prevalence, %
Fatigue 98
Dyspnea 86
Musculoskeletal pain 82
Mental fog (difficulty with concentration) 70
Increased sleep 56
Orthostatic intolerancea 34
Loss of smell or taste 30
Change in weight >10 lbb 12
aIncludes lightheaded/dizziness and syncope.
bIncludes 10% of patients with a decrease and 2% with an increase.

Table 2 presents selected CPX variables. Four patients exhibited pre-exercise sinus tachycardia (heart rates ≥100 beats per minute [bpm]). Pre-exercise systolic blood pressures of <100 mm Hg were measured in five patients. The most common limiting symptoms, other than fatigue, were dyspnea (27/50), chest discomfort (9/50), and lightheadedness/dizziness (8/50). Peak exercise systolic blood pressures of <130 mm Hg were observed in five individuals. Heart rate recovery at 1 min after peak exercise was abnormal, defined as <12 bpm,52 in nine patients. The V˙E/V˙co2 slope was >30, generally considered the upper limit of normal, in 14 patients.53 All patients exhibited a normal breathing reserve. None of the patients demonstrated arterial oxygen desaturation with exercise. Mean V˙o2peak was approximately 30% below predicted, with 24 patients (48%) <70% of predicted. Twenty-three patients had a V˙o2peak of <20 mL/kg/min. Four patients had a V˙o2peak of ≥90% of predicted (8%).

Table 2 - Selected Cardiopulmonary Exercise Test Variables for Post-COVID-19 Syndrome Patients (n = 50)
Variable Mean ± SD Range
Interval from COVID-19 diagnosis to CPX, mo 6.5 ± 1.6 3-12
Rest HR, bpm 72 ± 17 35-114
Peak HR, bpm 154 ± 23 109-200
Recovery HR, bpm 16 ± 7 −1-33
Pre-exercise systolic BP, mm Hg 120 ± 19 80-168
Peak systolic BP, mm Hg 165 ± 29 118-230
Respiratory exchange ratio peak exercise 1.2 ± 0.1 0.9-1.43
o 2peak, mL/kg/min 21.8 ± 5.5 13-40
Percent predicted V˙o 2peak 70.8 ± 14.6 38-114
Arterial oxygen saturation, minimum, % 97 ± 2 91-100
E/V˙co 2 slope 27 ± 4 18-36
Breathing reservea, % 46.7 ± 14.8 17-83
Abbreviations: BP, blood pressure; CPX, cardiopulmonary exercise testing; HR, heart rate; V˙o2peak, peak oxygen uptake.
aDifference between maximal voluntary ventilation and maximal exercise ventilation/maximal voluntary ventilation.

In summary, patients who were able to perform a CPX between 3 and 11 mo after COVID-19 demonstrated considerable variability in cardiopulmonary variables. Patients with persistent symptoms had a lower V˙o2peak than did patients without persistent symptoms. Data from multiple studies suggest that deconditioning, abnormal ventilation, and circulatory limitations all contribute to below normal cardiorespiratory fitness in symptomatic patients. For patients who met strict criteria for PCS, mean V˙o2peak was 30% below predicted and <10% of these patients had a normal value.

EXERCISE PRESCRIPTION AFTER COVID-19 INFECTION

There are no evidence-based guidelines for either returning to regular exercise in previously active persons or starting an exercise program for previously sedentary individuals after developing COVID-19 with or without PCS.54 However, there are general recommendations for exercise for these patients based on the consensus of a multidisciplinary team at Mayo Clinic and experts from other academic medical centers.55,56 The Mayo Clinic consensus group included input from the following disciplines: infectious disease, cardiology, sports cardiology, pulmonary and critical care medicine, physical medicine and rehabilitation, cardiac rehabilitation, exercise physiology, and internal medicine, and developed recommendations based on severity of illness (Box 1).54,57

Box 1 Definitions of Disease Severity (Asymptomatic/Mild, Moderate, and Severe)a

  1. For any patient with cardiopulmonary symptoms, referral to cardiology before returning to, or starting an exercise program is advised.
  2. Patients with asymptomatic or mild illness (no dyspnea or abnormal chest imaging) should refrain from exercise for 10 d after symptom onset or a positive test. If there are no underlying medical conditions, return or start exercise gradually, based on exercise tolerance.
  3. Patients with moderate disease (evidence of lower respiratory disease with O2 saturations of ≥94% on room air at sea level) should not exercise for 10 d after symptom resolution.
  4. Patients with severe illness (O2 saturations of <94% on room air at sea level, respiratory rate >30 breaths/min) requiring hospitalization or supplemental oxygen should refrain from exercise for ≥14 d after resolution of symptoms. A physician or advanced practice provider should assess patient symptoms prior to starting exercise.
  5. Patients who have had myocardial injury, an acute coronary syndrome, or a life-threatening arrhythmia require cardiology clearance before exercise.

aFrom the National Institutes of Health.57

Activities of daily living, including short walks, taking stairs, etc, are reasonable for many patients during, or immediately after acute COVID-19 while avoiding formal exercise training as recommended previously. Recommendations for activities of daily living should be individualized with input from the primary health care providers of the patients.

It is advisable to closely monitor respiratory symptoms, as patients gradually begin and progress exercise training.58 In addition, intense exercise should be avoided in patients with persistent skeletal muscle discomfort. A gradual approach to beginning and progressing the dose of exercise allows ample opportunity for multisystem training adaptations to occur and to prevent worsening of symptoms such as prolonged post-exercise fatigue and the inability to recover fully within 24 hr after an exercise session. In general, patients who were physically active prior to mild to moderate infection may return to exercise training amounts recommended by national guidelines, such as from the American College of Sports Medicine,59 within a few days to weeks. Individuals who were sedentary prior to infection require more time to achieve guideline-directed amounts of exercise training.

SPECIFIC SUGGESTIONS FOR EXERCISE PRESCRIPTION FOR PATIENTS WITH POST-COVID-19 SYNDROME

Exercise training has been demonstrated to provide benefits in diseases similar to PCS in terms of symptomatology and pathophysiology, such as other post-viral syndromes and POTS.60 Regular exercise improves immunologic function, decreases pulmonary symptoms, and improves indices of cardiovascular fitness/health and psychological function.60

The following recommendations for exercise prescription (Box 2) for patients with PCS are based on our experience working with patients with previous coronavirus infections (severe acute respiratory syndrome [SARS 2003], middle east respiratory syndrome [MERS 2012])61 as well as our extensive experience with POTS.38

Box 2 Suggestions for Exercise Prescription

  1. Patients with PCS are diverse in terms of symptom severity, exercise capacity, and perceived functional decline relative to pre-illness abilities. Exercise program individualization is a must.
  2. Assessment of exercise capacity with either CPX or the 6-min walk test is advised.
  3. Patients with significant functional limitations benefit from physical and or occupational therapy prior to beginning a formal exercise program.
  4. Start with a small dose of exercise with a gradual progression of duration and intensity.
  5. Stop exercise if clinically significant symptoms occur, such as chest pain, palpitations, excessive HR, severe dyspnea, lightheadedness/dizziness, pre-syncope/syncope, excessive fatigue, peripheral edema, headache, and tunnel vision.
  6. Participation in supervised exercise in a cardiopulmonary rehabilitation program (center-based, home-based, or hybrid approach) is highly desirable. However, reimbursement may not be available and some rehabilitation staff may not be adequately prepared to treat patients with PCS.
  7. Aerobic exercise prescription specifics based on the acronym FITT-P (frequency, intensity, type, time, progression) are as follows:
    1. Frequency: daily; consider multiple brief (<10 min) daily sessions.
    2. Intensity: begin with lower intensity (Borg perceived exertion ratings [RPE] of 10-11 on the 6- to 20-point scale, HR <60% of maximum).
    3. Type: consider starting with non-weight-bearing modes of exercise for individuals with limited capacities and/or orthostatic symptoms: recumbent stationary cycle, recumbent stepper, rowing ergometer.
    4. Time: conservative duration at first: >5-10 min.
    5. Progression: Time: increase by 1-3 min/session, as tolerated with a goal duration of 30-45 min; intensity: gradually progress to moderate intensity (RPE 12-13, HR >80% of maximum); and further progress to moderate to higher intensity (RPE 14-17, HR >80% of maximum), as tolerated.
  8. Resistance exercise prescription specifics based on the FITT-P acronym:
    1. Frequency: 2-3 sessions/wk on nonconsecutive days.
    2. Intensity: perform 10-15 slow repetitions of each exercise, RPE 11-13 or 40-60% of one repetition maximum.
    3. Time: one to three sets of 8-10 exercises for the major muscle groups; initial focus should be on the lower extremities and body core for patients with POTS-like symptoms. For these patients, gradually add other exercises for the major muscle groups.
    4. Type: elastic bands, hand weights, body weight, and weight training machines.
    5. Progression: gradual progression of repetitions and resistance, as tolerated.

Abbreviations: CPX, cardiopulmonary exercise testing; HR, heart rate; PCS, post-COVID-19 syndrome; POTS, postural orthostatic tachycardia syndrome.

CONCLUSIONS

Although COVID-19 primarily damages the lungs, cardiovascular complications may result in considerable morbidity and mortality. The range of potential cardiovascular pathology resulting from the virus is broad and includes myocardial injury, acute coronary syndrome, myocarditis, stress cardiomyopathy, arrhythmias, HF, and cardiogenic shock. Patients who are more physically active and have greater maximal exercise capacities are less likely to experience severe COVID-19 illness and hospitalization if they contract the virus compared with their less active and lower fit peers. Unfortunately, PCS is common and may result in debilitating symptoms. Patients with PCS demonstrate variable cardiorespiratory fitness with a substantial portion exhibiting limited fitness. The most common limiting symptom during exercise for patients with PCS is dyspnea. Exercise training after COVID-19 infection should be individualized and generally begin conservatively and progress gradually.

REFERENCES

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733.
2. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141–154.
3. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782–793.
4. Dhakal BP, Sweitzer NK, Indik JH, Acharya D, William P. SARS-CoV-2 infection and cardiovascular disease: COVID-19 heart. Heart Lung Circ. 2020;29(7):973–987.
5. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811–818.
6. Florindo HF, Kleiner R, Vaskovich-Koubi D, et al. Immune-mediated approaches against COVID-19. Nat Nanotechnol. 2020;15(8):630–645.
7. Miesbach W, Makris M. COVID-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost. 2020;26:1076029620938149.
8. Ranard LS, Fried JA, Abdalla M, et al. Approach to acute cardiovascular complications in COVID-19 infection. Circ Heart Fail. 2020;13(7):e007220.
9. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
10. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;72(18):2231–2264.
11. Hendren NS, Drazner MH, Bozkurt B, Cooper LT. Description and proposed management of the acute COVID-19 cardiovascular syndrome. Circulation. 2020;141(23):1903–1914.
12. Babapoor-Farrokhran S, Gill D, Walker J, Rasekhi RT, Bozorgnia B, Amanullah A. Myocardial injury and COVID-19: possible mechanisms. Life Sci. 2020;253:117723.
13. Chung MK, Zidar DA, Bristow MR, et al. COVID-19 and cardiovascular disease: from bench to bedside. Circ Res. 2021;128(8):1214–1236.
14. Bienstock SW, Tandon P, Govindarajulu U, et al. Impact of myocardial injury in hospitalized patients with COVID-19 in 2 peak time periods. J Am Coll Cardiol. 2021;78(14):1482–1483.
15. Giustino G, Pinney SP, Lala A, et al. Coronavirus and cardiovascular disease, myocardial injury, and arrhythmia: JACC focus seminar. J Am Coll Cardiol. 2020;76(17):2011–2023.
16. De Rosa S, Spaccarotella C, Basso C, et al. Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era. Eur Heart J. 2020;41(22):2083–2088.
17. Garcia S, Albaghdadi MS, Meraj PM, et al. Reduction in ST-segment elevation cardiac catheterization laboratory activations in the united states during COVID-19 pandemic. J Am Coll Cardiol. 2020;75(22):2871–2872.
18. Solomon MD, McNulty EJ, Rana JS, et al. The COVID-19 pandemic and the incidence of acute myocardial infarction. N Engl J Med. 2020;383(7):691–693.
19. Helal A, Shahin L, Abdelsalam M, Ibrahim M. Global effect of COVID-19 pandemic on the rate of acute coronary syndrome admissions: a comprehensive review of published literature. Open Heart. 2021;8(1):e001645. doi:10.1136/openhrt-2021.
20. Mafham MM, Spata E, Goldacre R, et al. COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England. Lancet. 2020;396(10248):381–389.
21. Mahmud E, Dauerman HL, Welt FGP, et al. Management of acute myocardial infarction during the COVID-19 pandemic: a consensus statement from the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of cardiology (ACC), and the American College of Emergency Physicians (ACEP). Catheter Cardiovasc Interv. 2020;96(2):336–345.
22. Xiang D, Xiang X, Zhang W, et al. Management and outcomes of patients with STEMI during the COVID-19 pandemic in China. J Am Coll Cardiol. 2020;76(11):1318–1324.
23. Siripanthong B, Nazarian S, Muser D, et al. Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm. 2020;17(9):1463–1471.
24. Kim IC, Kim JY, Kim HA, Han S. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J. 2020;41(19):1859.
25. Gnecchi M, Moretti F, Bassi EM, et al. Myocarditis in a 16-year-old boy positive for SARS-CoV-2. Lancet. 2020;395(10242):e116.
26. Haussner W, DeRosa AP, Haussner D, et al. COVID-19 associated myocarditis: a systematic review. Am J Emerg Med. 2021;51:150–155.
27. Singh S, Desai R, Gandhi Z, et al. Takotsubo syndrome in patients with COVID-19: a systematic review of published cases. SN Compr Clin Med. 2020;2(11):2102–2108.
28. Li Z, Shao W, Zhang J, et al. Prevalence of atrial fibrillation and associated mortality among hospitalized patients with COVID-19: a systematic review and meta-analysis. Front Cardiovasc Med. 2021;8:720129.
29. Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(9):1036–1041.
30. Qin JJ, Cheng X, Zhou F, et al. Redefining cardiac biomarkers in predicting mortality of inpatients with COVID-19. Hypertension. 2020;76(4):1104–1112.
31. Tavazzi G, Pellegrini C, Maurelli M, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911–915.
32. Irabien-Ortiz A, Carreras-Mora J, Sionis A, Pamies J, Montiel J, Tauron M. Fulminant myocarditis due to COVID-19. Rev Esp Cardiol (Engl Ed). 2020;73(6):503–504.
33. Sallis R, Rohm Young D, Tartof SY, et al. Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48,440 adult patients. Br J Sports Med. 2021;55(19):1099–1105.
34. Brawner CA, Ehrman JK, Bole S, et al. Inverse relationship of maximal exercise capacity to hospitalization secondary to coronavirus disease 2019. Mayo Clin Proc. 2021;96(1):32–39.
35. Phillips S, Williams MA. Confronting our next national health disaster—long-haul COVID. N Engl J Med. 2021;385(7):577–579.
36. Mayo Clinic. Post-COVID-19 syndrome. https://askmayoexpert.mayoclinic.org/topic/clinical-answers/gnt-20511319/sec-20511329.
37. Radin JM, Quer G, Ramos E, et al. Assessment of prolonged physiological and behavioral changes associated with COVID-19 infection. JAMA Netw Open. 2021;4(7):e2115959.
38. Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc. 2012;87(12):1214–1225.
39. Taquet M, Dercon Q, Luciano S, et al. Incidence, co-occurrence, and evolution of long-COVID features: a 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLoS Med. 2021;18(9):e1003773.
40. Logue JK, Franko NM, McCulloch DJ, et al. Sequelae in adults after COVID-19 infection. JAMA Netw Open. 2021;4(2):e210830. doi:10.1001/jamanetworkopen.2021.0830.
41. FAIR Health. A Detailed Study of Patients with Long-Haul COVID. New York, NY: FAIR Health; 2021.
42. Centers for Disease Control and Prevention. COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#datatracker-home.
43. Arena R, Myers J, Kaminsky LA. Cardiopulmonary exercise testing algorithm for viral infection: assessing health risk and short- to long-term effects. J Cardiopulmonary Rehabil Prev. 2021;41(4):E7–E8.
44. Skjorten I, Wathne Ankerstjerne OA, Trebinjac D, et al. Cardiopulmonary exercise capacity and limitations 3 months after COVID-19 hospitalization. Eur Respir J. 2021;58(2):2100996.
45. Rinaldo RF, Mondoni M, Parazzini EM, et al. Deconditioning as main mechanism of impaired exercise response in COVID-19 survivors. Eur Respir J. 2021;58(2):2100870. doi:10.1183/13993003.00870-2021.
46. Jahn K, Sava M, Sommer G, et al. Exercise capacity-impairment after COVID-19 pneumonia is mainly caused by deconditioning. Eur Respir J. 2021;59(1):2101136. doi:10.1183/13993003.01136-2021.
47. Barbagelata L, Masson W, Iglesias D, et al. Cardiopulmonary exercise testing in patients with post-COVID-19 syndrome. Med Clin (Barc). 2021;S0025-7753(21)00462-0. doi:10.1016/j.medcli.2021.07.007.
48. Alba GA, Ziehr DR, Rouvina JN, et al. Exercise performance in patients with post-acute sequelae of SARS-CoV-2 infection compared to patients with unexplained dyspnea. EClinicalMedicine. 2021;39:101066.
49. Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of cardiopulmonary stress testing for patients with unexplained dyspnea post-coronavirus disease. JACC Heart Fail. 2021;9(12):927–937.
50. Singh I, Joseph P, Heerdt PM, et al. Persistent exertional intolerance after COVID-19: insights from invasive cardiopulmonary exercise testing. Chest. 2022;161(1):54–63.
51. Skalski J, Allison TG, Miller TD. The safety of cardiopulmonary exercise testing in a population with high-risk cardiovascular diseases. Circulation. 2012;126(21):2465–2472.
52. Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med. 1999;341(18):1351–1357.
53. Arena R, Myers J, Harber M, et al. The VE/VCO2 slope during maximal cardiopulmonary exercise testing: reference standards from FRIEND (fitness registry and the importance of exercise: a national database). J Cardiopulmonary Rehabil Prev. 2021;41(3):194–198.
54. Salman D, Vishnubala D, Feuvre P, et al. Returning to physical activity after COVID-19. Brit Med J. 2021;372:1–6.
55. Mayo Clinic. COVID-19: postinfection return to exercise (adult). https://askmayoexpert.mayoclinic.org/topic/clinical-answers/gnt-20507347/cpm-20507354.
56. Cleveland Clinic. Returning to Sports or Exercise After Recovering From COVID-19. https://health.clevelandclinic.org/returning-to-sports-or-exercise-after-recovering-from-covid-19/
57. National Institutes of Health. Clinical Spectrum of SARS-CoV-2 Infection. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/
58. Metzl JD, McElheny K, Robinson JM, et al. Considerations for return to exercise following mild-to-moderate COVID-19 in the recreational athlete. HSS J. 2020;16(suppl 1):102–107. doi:10.1007/s11420-020-09777-1.
59. American College of Sports Medicine. ACSM's Guidelines for Exercise Testing and Prescription. 11th ed. Philadelphia, PA: Wolters Kluwer, 2022.
60. Jimeno-Almazan A, Pallares JG, Buendia-Romero A, et al. Post-COVID-19 syndrome and the potential benefits of exercise. Int J Environ Res Public Health. 2021;18(10):5329.
61. Vanichkachorn G, Newcomb R, Cowl CT, et al. Post-COVID-19 syndrome (long haul syndrome): a multidisciplinary clinic at Mayo Clinic and characteristics of the initial patient cohort. Mayo Clin Proc. 2021;96(7):1782–1791.
Keywords:

cardiac complications; cardiopulmonary exercise testing; COVID-19; exercise prescription after acute viral infection

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