*6.9. Peripheral Arterial Disease*

## 6.9.1. Rationale

Peripheral arterial disease (PAD) is a progressive disease caused by atherosclerosis and results in limited blood flow and oxygen delivery to the lower limbs, as well as skeletal muscle dysfunction [70]. The most recognizable symptom of PAD is intermittent claudication (IC), occurring in 30% of patients with PAD [71]. Exercise-based cardiac rehabilitation reduces symptoms, prolongs claudication distance, and improves the quality of life in patients with peripheral arterial disease by the improvement in the metabolism of skeletal muscles, blood redistribution, and rheological changes [72]. Although cardiac rehabilitation leads to significant improvements in walking distance, no clear evidence regarding mortality reduction has been demonstrated [73].

### 6.9.2. Exercise Testing

Exercise tests are typically performed on a treadmill. The following are recorded [74]:


Thus, both the pain-free walking distance and cardiorespiratory fitness level should be evaluated. The graded stress test is the preferred mode of testing, with the maximal distance (and time), rather than the onset of claudication, recorded. Numerous testing protocols exist [75]:


The ankle–brachial index (ABI) is the ratio of the blood pressure at the ankle level to the blood pressure measured in the upper arm. ABI is used to objectively classify the severity of peripheral arterial disease, with ABI < 0.5 corresponding to low physical activity and reflecting significant stenosis, ABI 0.2–0.49 corresponding to rest pain, and ABI less than 0.2 reflecting tissue necrosis [7]. A decrease in the ankle–brachial index in response to the treadmill test reflects significant stenosis [76].

### 6.9.3. Exercise Training

Weight-bearing exercises such as walking are preferred, and training intensity can be determined with relation to the start of claudication, achieving maximal march distance, or achieving vasodilation. Most of the existing programs utilize the model of interval walking until near maximal pain, with a modulation of speed and/or grade to induce the onset of claudication within 3–5 min and moderate to moderately severe claudication within 8–10 min. Once pain is experienced, patients are encouraged to rest and repeat the bout of exercise when their symptoms resolve. A walking exercise duration of 30–60 min and a program duration of at least 12 weeks are recommended [7,77]. Popular protocols utilize a walking speed of 4.6 km/hour, with inclination adjusted so as not to provoke pain within 3 min and a total program duration of 6 months or walking at 4 km/hour without inclination and with further speed adjustment if the patient can complete a 10 min walk without experiencing pain. Programs with walking despite pain increase claudication distance; however, patients' training adherence remains suboptimal due to pain [78]. Moreover, the potential harmful effects of this training principle include provoking inflammatory damage in the endothelium. The alternative approach of pain-free walking can elicit similar benefits, according to data derived from a small study [79] where the authors utilized a pain-free "2/3 claudication distance" formula. One cycle comprised 3 to 5 walks, with 1–3 min rests between them, 3 times a day, 5 days a week, for at least 12 weeks. With training progression and increasing claudication distance, regular re-testing can be performed on a weekly basis [80].

Although walking is the most efficacious mode of training, cycle ergometer exercise is utilized in selected patients—e.g., those with obesity or gait problems [72].

Resistance training starting with an intensity of 30%–50% of 1-RM, including 2–3 sets, and with regular progression every 2–4 weeks for a total time period of 6 months is recommended [7].

### *6.10. COVID-19*

### 6.10.1. Introduction

Coronavirus disease 19, known as COVID-19, is a contagious, highly transmissible disease caused by severe acute respiratory syndrome coronavirus 2 [81]. The rapid spread of COVID-19 caused a pandemic, leading to more than 6 million deaths (March 2022), affecting global health care systems and economies, and causing governments to impose multiple restrictions. COVID-19 induces a state of systemic inflammation with enhanced oxidation; evoked systemic inflammatory status, termed a cytokine storm, can result in multi-organ failure [82,83].

The clinical picture of COVID-19 fluctuated from asymptomatic or mild respiratory symptoms to severe life-threatening pneumonia and respiratory and cardiac failure [84]. Typical COVID-19 manifestations observed in computed tomography images of the chest included ground-glass opacities and air bronchogram signs [85]. The most vulnerable group of patients were immunocompromised and older adults with underlying diseases [86]. COVID-19 affects the cardiovascular system by attachment to cells utilizing membrane protein angiotensin-converting enzyme 2, with subsequent internalization and interaction between proteins and viral ribonucleic acid [83]. As angiotensin-converting enzyme 2 is widely expressed in many human tissues—e.g., in the lungs and heart—viral penetration causes diffuse, multiorgan damage [87]. Numerous studies have found a strong link between preexisting cardiovascular disease and poor outcomes in patients with COVID-19.

### 6.10.2. Cardiac Manifestations of the COVID-19

It has been documented that COVID-19 is responsible for the induction of myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism. Cardiac injury, including elevated troponin level, and ECG or echocardiographic abnormalities have been reported in many studies, with COVID-19 cardiac involvement being documented in 7–28% of hospitalized COVID-19 patients [88]. Cardiac complications are multifactorial and may be result of myocardial damage, hypoxia, the dysfunction of the angiotensin-converting enzyme 2 receptor, or systemic inflammatory status [89]. Heart failure and myocarditis have been reported, respectively, in 10–52% and 8–12% of patients hospitalized for COVID-19 [90]. A specific COVID-19-related cardiac condition is Takotsubo stress cardiomyopathy, with the presence of mid-left ventricular segments hypokinesis [91]. Arrhythmias occurred in the acute phase of COVID-19, and the most common arrhythmia was atrial fibrillation; however, the occurrence of sustained ventricular tachycardia has been reported in 5–6% of hospitalized patients [92]. Moreover,

patients with COVID-19 remained at higher risk of thromboembolic complications due to coagulopathy [93].
