Cardiac Emergencies: Assessment

• Diaphoresis, nausea, and vomiting frequently accompany chest discomfort associated with ACS but are not predictive of ACS.
• Elderly patients with ACS may only complain of symptoms other than CP, such as:
  • Altered mental status
  • Dyspnea
  • Syncope
  • Weakness
• Symptoms, such as diaphoresis and nausea, may also occur with nonischemic CP, including:
  • Acute heart failure
  • Aortic dissection
  • Esophageal spasm
  • PE

• Acute aortic dissection has a wide range of potential associated symptoms, depending on the arterial branches involved, which may confound the diagnosis.
• According to one review, syncope accompanies 13% of dissections involving the ascending aorta.
• Neurological symptoms, ranging from hoarseness to paraplegia and altered mental status, occur in 18% to 30% of patients with aortic dissection.
• ACS can occur when the dissection involves the coronary arteries.

• Dyspnea frequently accompanies pulmonary causes of CP and may be the predominant symptom in:
  • PE
  • Pneumonia
  • Pneumothorax
• Tachypnea is common with PE and may be accompanied by wheezing and fever.
• Young, healthy patients may manifest only relative tachypnea or tachycardia despite the presence of pneumonia or PE.
• Dyspnea is often the only complaint among elderly patients with ACS.
• Cough, syncope, and hemoptysis may occur with PE and valvular heart disease (particularly mitral stenosis).
• Cough and hemoptysis are more common with bronchitis, pharyngitis, or exacerbations of COPD.
• Dyspnea and cough may accompany pericardial and pleural effusions regardless of etiology.
• Nausea and belching frequently accompany gastrointestinal causes of CP but can also occur in patients with an inferior MI.
• Palpitations experienced.
• Fever raises concern for infectious causes but is also associated with:
  • Acute MI (rarely)
  • Myocarditis
  • Pericarditis
  • PE (usually low-grade)
• Inquire about preceding or concomitant symptoms, such as fever or peripheral edema.
• Preceding or concomitant pain and swelling in an extremity suggests deep venous thrombosis (DVT) complicated by PE.
  • DVT occurs most often in the lower extremities, but clots may also originate in the upper extremities and the large veins of the pelvis, where they may produce bilateral lower extremity swelling if the inferior vena cava becomes occluded.

Inquire about risk factors for life-threatening illness, including:

• ACS
• Acute aortic dissection
• PE

Inquire about comorbidities such as:

• Bicuspid aortic valve
• Connective tissue disorders
• Current or recent pregnancy
• Diabetes Mellitus (DM)
• Hypertension (HTN)
• Malignancy
• Peripheral Arterial Disease (PAD)

• Inquire about recent events such as:
  • Diagnostic procedures (such as endoscopy, aortic catheterization)
• Many patients with CP have undergone diagnostic testing for prior episodes, the results of which may be useful.
  • For example, a recent cardiac catheterization or coronary CT angiogram with normal or minimally diseased vessels virtually eliminates the possibility of an ACS.
  • An observational study of 1,977 consecutive patients with coronary arteriograms documenting minimal (i.e., less than 25%) stenosis or normal coronary arteries found that 98% of these patients were free of MI 10 years later. Other studies confirm this data (Hollander & Chase, 2021).
  • Conversely, a prior negative stress test is not useful to rule out ACS in patients with active CP.
• Major surgery
• Past physical trauma

• Inquire about family history of CP
• Also ask about family history of heart disease, lung disease, or any of the above life-threatening emergencies that often present with CP

• Inquire about drug use (cocaine etc.)
• Ask about use of cigarettes and other forms of tobacco/nicotine
• Recent periods of immobilization (long plane ride, etc.)

The natural history of new-onset angina depends in part upon the degree of exertion required to induce CP.

• Patients with new-onset angina occurring only after heavy physical exertion, such as shoveling snow or lifting a 50-pound weight, have a prognosis similar to patients with chronic stable angina.
• In comparison, new angina occurring after minimal exercise or at rest, particularly if prolonged, carries a worse prognosis in the absence of intervention.

Rest angina, particularly prolonged or associated with transient ST-segment changes >0.05 mV, identifies patients at increased risk.

Early post-infarction angina (defined as CP occurring within 48 hours after an acute MI) is typically associated with complex lesions, persistent intracoronary thrombus, and more severe coronary disease.

The recurrent CP may signify either remaining viable myocardium in the infarct zone or a different area of myocardium at risk. Angina occurring soon after an acute MI is associated with high risk in the absence of intervention (Simons & Alpert, 2021).

Patients with recurrent ischemia that was refractory or responsive to medical therapy had a higher rate of reinfarction at 30 days and six months (Simons & Alpert, 2021).

Additionally, refractory ischemia was associated with higher mortality than responsive ischemia or no ischemia at 30 days and one year (Simons & Alpert, 2021).

Angina after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) can reflect a procedural event. In addition, over the long-term, restenosis after PCI, stenosis in a graft (usually with saphenous vein grafts), or progression of the native disease can also result in post-CP.

Periprocedural Angina:

A periprocedural ischemic event may occur with or without symptoms, with or without troponin elevation, and either at the site of PCI or remotely (Simons & Alpert, 2021).

Ischemic CP (with or without troponin elevation) within 48 hours after stenting usually results from:

• Distal embolization of atherosclerotic or thrombotic debris.
• Procedural events such as abrupt vessel closure (usually due to stent thrombosis or progression of an untreated dissection).
• Side branch occlusion.
• Transient coronary spasm.

Other patients have asymptomatic enzyme elevations indicative of procedural-related myocardial injury of a type 4 MI if the troponin level is above five times the upper reference limit. There is clinical evidence of ischemia on the ECG or an event during or after, or after the event after PCI, such as stent thrombosis (Simons & Alpert, 2021). On occasion, periprocedural ischemia early after PCI may occur at the stenotic lesions not addressed at the time of the procedure. It is important to note that ECG changes are associated with a worse prognosis (Simons & Alpert, 2021).

An important diagnostic consideration soon after PCI is the distinction between ischemic and nonischemic CP.

• Nonischemic CP is typically manifested at rest, without ECG changes or elevation of cardiac enzymes.
• Most patients describe pain characteristics different from their typical angina (more localized and frequently pleuritic). This discomfort lasts for less than 72 hours in about 80% of patients and less than two weeks in the remainder (Simons & Alpert, 2021). Overexpansion of the stent is thought to be responsible in most cases (Simons & Alpert, 2021).

Recurrent angina during the postoperative period after a CABG is usually due to a technical problem with a graft or with early graft closure (Simons & Alpert, 2021). It is, therefore, an indication for prompt catheterization with revascularization by PCI, if feasible. The diagnosis of recurrent ischemia may be difficult after a CABG since cardiac enzyme elevations occur due to the surgical procedure, and ECG changes may reflect postoperative pericardial inflammation (Simons & Alpert, 2021).

Late Angina:

The delayed onset of angina (30 days or more after PCI) can reflect restenosis after PCI, graft stenosis after CABG, or progression of the native disease (Simons & Alpert, 2021). Affected patients typically present with the gradual and progressive return of effort angina. Prompt stress testing should be performed since these patients are at increased risk.

While less common, some patients with recurrent ischemia present with UA. Such patients should be evaluated with cardiac catheterization after adequate medical stabilization (Simons & Alpert, 2021).

NSTEMI can also occur in patients with prior CABG. These patients have an increased rate of significant coronary events. The older the saphenous vein graft, the higher the likelihood that UA is due to a culprit lesion within the graft. Grafts are more likely than native vessels to show total occlusion or thrombus, complications that are more refractory to medical therapy (Simons & Alpert, 2021). Among patients who undergo PCI for saphenous vein graft disease, restenosis is manifested by UA presentation in 25% of patients (Simons & Alpert, 2021).

Ischemic pain is typically gradual in onset, although the intensity of the discomfort may wax and wane.

Ischemic pain is generally provoked by activity, such as exercise, that increases cardiac oxygen demand. Ischemic pain does not change with respiration or position. It may or may not respond to nitroglycerin and, if there is an improvement, this may only be temporary. Relief of ischemic pain following the administration of therapeutic interventions (e.g., nitroglycerin, "gastrointestinal cocktail" of viscous lidocaine, and antacid) does not reliably distinguish nonischemic from ischemic CP.

Ischemic pain is often characterized more like discomfort than pain and it may be difficult for the patient to describe. Terms frequently used by patients to describe ischemic pain include:

• Ache
• Band-like sensation
• Burning
• Constriction
• Crushing
• Fullness in the chest
• Heartburn
• Heavy weight on chest (elephant sitting on chest)
• Knot in the center of the chest
• Like a bra too tight
• Lump in throat
• Pressure
• Strangling
• Squeezing
• Tightness
• Toothache (when there is radiation to the lower jaw)

Ischemic pain is not generally described as sharp, fleeting, knife-like, stabbing, or like "pins and needles." Increased pain severity does not appear to correlate with an increased likelihood of acute MI. In some cases, the patient cannot qualify the nature of the discomfort but places their clenched fist in the center of the chest, known as the "Levine sign” (Reeder et al., 2021).

Ischemic pain often radiates to other parts of the body, including:

• Arms (upper and forearm)
• Back (specifically the interscapular region)
• Fingers
• Lower jaw and teeth (but not upper jaw)
• Neck
• Shoulders
• Throat
• Upper abdomen (epigastrium)
• Wrist

The old dictum that "pain above the nose or below the navel is rarely cardiac in origin" still holds. Pain radiating to the upper extremities is highly suggestive of ischemic pain (Reeder et al., 2021).

Ischemic pain is not felt in one specific spot. Ischemic pain is a diffuse discomfort that may be difficult to localize. The patient often indicates the entire chest rather than localizing it to a specific area by pointing a single finger.

Angina is usually brief (two to five minutes) and is relieved by rest or with nitroglycerin.

In comparison, patients with an ACS may have CP at rest and the duration is variable but generally lasts longer than 30 minutes. Classic anginal pain lasting more than 20 minutes suggests ACS. Continuous pain that does not wax and wane and persists for over 24 hours is unlikely due to ACS (Reeder et al., 2021).

For spontaneous dissection, it is uncertain whether the initiating event is a primary rupture of the intima with secondary dissection of the media or primary hemorrhage within the media and subsequent rupture of the overlying intima.

The initial intimal tear can occur in the ascending or descending aorta and occasionally originate in the abdominal aorta. This tear occurs when (Black & Manning, 2021a):

• Blood at high pressure passes through the tear and separates the intima from the media or adventitia, creating a false lumen.
• The dissection can propagate proximally or distally from the initial tear to involve the aortic valve, coronary arteries, or thoracic or abdominal aorta branches.
  • Such propagation is responsible for many associated clinical features of aortic dissection (acute CP or back pain, neurologic symptoms).
  • A higher mean pressure in the false lumen can cause dynamic or static compression and occlusion of the true lumen with malperfusion of the aorta branches, resulting in end-organ ischemia (coronary, cerebral, spinal, extremity, visceral).
  • Aortic regurgitation, coronary ischemia, and cardiac tamponade can occur if the dissection progresses proximally to involve the aortic valve and coronary arteries or the pericardial sac.
  • Additionally, multiple communications may form between the true lumen and the false lumen.

Abdominal aortic dissection can occur as an extension to a thoracic aortic dissection with the intimal flap located in the proximal or descending thoracic aorta, or it can occur in isolation (Black & Manning, 2021a):

• Isolated abdominal aortic dissection is reported occasionally and can be due to spontaneous, iatrogenic, or traumatic mechanisms.
• The infrarenal abdominal aorta is more commonly involved than the suprarenal aorta.
  • In one review of 52 reported cases, the entry site for spontaneous isolated abdominal aortic dissections (SIAADs) most commonly occurred between the renal arteries and inferior mesenteric artery.
    • A concomitant abdominal aortic aneurysm was identified in 40% of patients and indicated the need for repair.

Aortic dissection that does not occur spontaneously can be due to instrumentation or trauma (Black & Manning, 2021a). Traumatic tears typically involve the descending thoracic aorta just distal to the subclavian artery. Iatrogenic or traumatic injury (e.g., intra-aortic balloon pump placement, rapid deceleration motor vehicle accident) was responsible for 6% of cases of intramural aortic hematoma in one review (Black & Manning, 2021a).

Aortic intramural hematoma is defined as a hematoma confined within the medial layer of the aorta in the absence of a detectable intimal tear, although microtears may be present (Black & Manning, 2021a). A rupture of the vasa vasorum probably produces the false channel into the media of the aortic wall. It can occur in the absence of significant atherosclerosis or with a concomitant atherosclerotic ulcer.

The absence of an intimal lesion distinguishes intramural aortic hematoma from the hematoma that may be associated with a penetrating aortic ulcer, for which there is a clear break in the intima (Black & Manning, 2021a). Aortic intramural hematoma can be a precursor to acute aortic dissection. In different series, intramural aortic hematoma accounted for 5% to 20% of patients with symptoms consistent with aortic dissection (e.g., acute aortic syndrome) (Black & Manning, 2021a).

The mechanism by which an intramural hematoma is created is not certain. Two mechanisms have been described (Black & Manning, 2021a):

1. Rupture induced by a penetrating atherosclerotic ulcer
2. Spontaneous rupture
   • Spontaneous rupture of the vasa vasorum as pathogenesis has not been proven
     • In this scenario, the false lumen originates from spontaneous rupture of the vasa vasorum into the media of the aortic wall because there is no continuous flow. The blood contained within the wall quickly thromboses

Some believe that intramural hematoma represents acute aortic dissection with thrombosis of the false lumen and that an intimal tear is always present whether or not it is identified (Black & Manning, 2021a). Intimal defects have been identified surgically and radiographically in approximately 70% of cases initially diagnosed as intramural hematoma (Black & Manning, 2021a). However, there appears to be a difference in the affected plane of the aortic media. The outer media (toward the adventitia) is thinner for intramural hematoma, which may explain the higher risk of rupture for intramural hematoma than acute dissection. Between 8% and 16% will evolve into the aortic dissection (Black & Manning, 2021a).

Intimal tear without hematoma is an uncommon variant of aortic dissection characterized by a stellate or linear intimal tear associated with exposure of the underlying aortic media or adventitial layers (Black & Manning, 2021a). There is no separation of the medial layers or progression. Blunt aortic injury with focal tear may manifest in this manner.

Penetrating aortic ulcer refers to a region of the aorta (ulcer-like projection) where the aortic intima is denuded with the lesion progressing through a variable amount of the aortic wall, over which there may or may not be overlying thrombus (Black & Manning, 2021a). Penetrating aortic ulcers are typically associated with atherosclerotic changes of the adjacent aortic wall (Black & Manning, 2021a). These ulcers may be associated with hematoma within the media and may progress to perforation or aortic dissection. Penetrating aortic ulcer is the initiating lesion in <5% of all aortic dissections (Black & Manning, 2021a).

Periaortic hematoma represents a contained aortic rupture due to slow oozing from the damaged aorta at or near the site of aortic injury (Black & Manning, 2021a). Periaortic hematoma is more common in intramural aortic hematoma compared with acute aortic dissection. In a review of 971 patients with acute dissections from the International Registry of Acute Aortic Dissections (IRAD), 227 (23%) had a periaortic hematoma (Black & Manning, 2021a). Not surprisingly, patients with periaortic hematoma had higher shock rates, cardiac tamponade, altered consciousness/coma, and a significantly higher mortality rate than those without a periaortic hematoma (Black & Manning, 2021a).

Aortic dissection is, somewhat arbitrarily, classified as acute or chronic based upon the duration of symptoms at the time of presentation (Black & Manning, 2021a). During the first two weeks (acute phase), life-threatening complications due to branch involvement or aortic rupture are more likely to occur than the past two weeks (chronic phase).

The two main anatomic classifications used to describe aortic dissection are the (Black & Manning, 2021a):

1. DeBakey System (Figure 1):
   • The DeBakey system is based upon the site of origin, with:
     • Type I involving the ascending aorta, arch, and descending thoracic aorta and may progress to involve the abdominal aorta.
     • Type 2 originating in and is confined to the ascending aorta.
     • Type IIIa involving the descending thoracic aorta distal to the left subclavian artery and proximal to the celiac artery.
     • Type IIIb dissection involving the thoracic and abdominal aorta distal to the left subclavian artery.
2. Stanford (Daily) System (Figure 1):
   • The Stanford system is more widely used and classifies dissections that involve the ascending aorta (and may also involve the arch or descending aorta) as:
     • Type A involving the ascending aorta and may progress to involve the arch and thoracoabdominal aorta.
     • Type B involving the descending thoracic or thoracoabdominal aorta distal to the left subclavian artery without the involvement of ascending aorta.

Figure 1: DeBakey and Stanford Systems

Type A ascending aortic dissections are almost twice as common as type B descending dissections (Black & Manning, 2021a). The right lateral wall of the ascending aorta is the most common site. In patients with an ascending aortic dissection, aortic arch involvement occurs in up to 30% (Black & Manning, 2021a).

Isolated abdominal aortic dissection is reported and can be due to iatrogenic, spontaneous, or traumatic mechanisms. The infrarenal abdominal aorta is more commonly involved than the suprarenal aorta. In one review of 52 reported cases, the entry site for spontaneous isolated abdominal aortic dissections (SIAADs) commonly occurred between the renal and inferior mesenteric arteries (Black & Manning, 2021a). A concomitant abdominal aortic aneurysm was identified in 40% of patients and indicated the need for repair (Black & Manning, 2021a).

• The Society for Vascular Surgery (SVS) and Society for Thoracic Surgery (STS) classification system is similar to the Stanford system distinguishing type A from type B by the level of involvement. Still, it also specifies the distal extent of the dissection.

Degenerative:

• Aortic dissection that has a degenerative etiology is not associated with any known genetically-mediated syndromes.

Genetically-mediated:

• Genetically mediated thoracic aortic aneurysm/dissection (TAAD) can be part of a syndrome:
  • Syndromic, such as Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, or Turner syndrome
  • Nonsyndromic, as with familial TAAD or bicuspid aortic valve

Traumatic:

• Traumatic aortic dissection can be related to a blunt injury mechanism or iatrogenic related to instrumentation (e.g., catheterization, dissection following aortic repair).

The most important predisposing factor for acute aortic dissection is systemic HTN. In the IRAD review, 76.6% had a history of HTN (Black & Manning, 2021a). HTN was more common in those with a distal (type B) dissection compared with a type A dissection. An abrupt, transient, severe increase in blood pressure has been associated with acute aortic dissection through various mechanisms.

Crack cocaine, which may cause transient HTN due to catecholamine release, accounted for 37% of dissections in an inner-city population report (Black & Manning, 2021a). The mean duration from last cocaine use to the onset of symptoms was 12 hours.

High-intensity weightlifting or other strenuous resistance training can also cause a transient elevation in blood pressure and has been reported as an antecedent (Black & Manning, 2021a).

HTN is also the postulated mechanism when energy drinks or ergotism have been associated with aortic dissection.

Genetically-mediated connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome) weaken the structural architecture of the aortic wall. In an IRAD review, Marfan syndrome was present in 50% of those under age 40, compared with only 2% of older patients (Black & Manning, 2021a). Most patients with Marfan syndrome and aortic dissection have a family history of dissection. There may also be an association between Marfan syndrome and aortic dissection in the third trimester of pregnancy (Black & Manning, 2021a).

In an IRAD review, 13% of patients had a known aortic aneurysm before dissection (Black & Manning, 2021a). The ascending aorta was more often the site of origin of the dissection than the aortic arch or descending aorta. Such a history was more common in patients under age 40. In a later IRAD review, a known aortic aneurysm was present in 20.7% of patients identified with descending aortic dissection and 12.7% of those with ascending aortic dissection (Black & Manning, 2021a).

In an IRAD review, 9% of patients under age 40 with aortic dissection had a bicuspid valve, compared with 1% of those over age 40 and 1% in the general population (Black & Manning, 2021a). Aortic dissection in patients with a bicuspid valve always involves the ascending aorta, usually with severe loss of elastic fibers in the media. The predisposition to dissection may reflect a genetic cause for the defect in the aortic wall, as enlargement of the aortic root or ascending aorta is frequently associated with bicuspid aortic valves, even those that function normally, independent of their function (Black & Manning, 2021a).

Cardiac surgery or catheterization for coronary or valvular disease can be complicated by aortic dissection. Cardiac catheterization, particularly with femoral artery access, with or without coronary intervention was reported to cause 14 of 723 dissections in a report from IRAD (Black & Manning, 2021a). Ascending aortic dissection is a rare complication of CABG, occurring with both conventional on-pump CABG and, perhaps more often, with minimally invasive off-pump CABG. In a review from a single institution, ascending aortic dissection occurred in 1 of 2,723 patients treated with conventional CABG and 3 of 308 undergoing off-pump CABG (Black & Manning, 2021a). Although rare, other procedures that manipulate the aorta, including carotid or other great vessel interventions and thoracic or abdominal aortic repair (open or endovascular), can also be complicated by aortic dissection.

Aortic dissection can occur in patients with an aortic coarctation when surgery leaves behind abnormal para coarctation aorta with intrinsic medial faults or when balloon dilatation of native coarctation mechanically damages the inherently abnormal para coarctation aorta (Black & Manning, 2021a).

TAAD refers to patients with thoracic aortic disease associated with a family history of aneurysmal disease but does not meet strict criteria for known connective tissue syndromes (Black & Manning, 2021a). The ascending thoracic aorta is predominantly involved.

Aortic dissection or rupture, often occurring with coarctation, is an increasingly recognized cause of death in women with Turner syndrome. In a survey of 237 patients, at least 15 had aortic dilation (Black & Manning, 2021a). In this survey, all of these cases involved the ascending aorta, 12 individuals had an associated risk factor such as HTN or another cardiovascular malformation (e.g., coarctation), and two individuals had a dissection (Black & Manning, 2021a).

The follow diseases that cause vasculitis include (Black & Manning, 2021a):

• Giant cell arteritis
• Rheumatoid arthritis
• Syphilitic aortitis
• Takayasu arteritis

Trauma rarely causes a classic dissection but can induce a localized tear in the region of the aortic isthmus. More commonly, chest trauma from acute deceleration (as in a motor vehicle accident) results in aortic rupture or transection (Black & Manning, 2021a).

Pregnancy and delivery are independent risk factors for aortic dissection. However, the presence of other conditions (e.g., bicuspid aortic valve, Marfan syndrome) may compound the risk. In one review, postpartum aortic dissection occurred in 2 of 31 Marfan pregnancies (Black & Manning, 2021a). A cohort study of administrative claims data, in several states from 2005 through 2013, found a rate of aortic complications of 5.5 per million patients during pregnancy and the postpartum period (Black & Manning, 2021a).

Pregnancy was associated with a significantly increased risk of aortic dissection or rupture than the control period one year later among women with and without documented inherited connective tissue diseases (e.g., Marfan syndrome). However, the risk was significantly greater in those with connective tissue diseases. The authors noted that the findings might reflect prevalent but undiagnosed or undocumented connective tissue disorders, or they may indicate that the physiologic changes of pregnancy can cause aortic injury even in otherwise healthy women (Black & Manning, 2021a).

Observational studies have suggested that fluoroquinolone use may be associated with an increased risk of aortic aneurysm or dissection (Black & Manning, 2021a).

Acute aortic dissection has a wide range of potential associated symptoms, depending on the arterial branches involved, which may confound the diagnosis (Black & Manning, 2021a). The symptoms and signs of acute aortic dissection depend upon the extent of the dissection and the affected cardiovascular structures.

HTN is present in 70% of type B dissections but only in 25% to 35% of type A dissections (Black & Manning, 2021). The presence of hypotension complicating a type B dissection is rare, seen in less than 5% of patients, and usually implies rupture of the aorta (Black & Manning, 2021a). By contrast, hypotension may be present in 25% of dissections involving the ascending aorta, potentially resulting from aortic valve disruption leading to severe aortic regurgitation or extravasation into the pericardial space leading to cardiac tamponade (Black & Manning, 2021a). Malperfusion of brachiocephalic vessels by the dissection may falsely depress brachial cuff pressures, usually by involving the left subclavian artery origin in the type B dissection patient (Black & Manning, 2021a).

The most common presenting symptom is pain occurring in over 90% of patients, with 85% noting the onset to be abrupt(Black & Manning, 2021a). Typically, the pain is severe and sharp/knife-like, causing the patient to seek medical attention within minutes to hours of onset, and categorically unlike any pain experienced before (Black & Manning, 2021a).

Pain can occur in isolation or be associated with syncope, a CVA, ACS, heart failure, or other clinical symptoms or signs. ACS can occur when the dissection involves the coronary arteries. The pain is typically described in the anterior chest in an ascending (type A) dissection, but for descending (type B) dissection, the pain is more often experienced in the back.

CP was significantly more common in patients with type A dissections in an IRAD review, while both back pain and abdominal pain were significantly more common with type B dissections (Black & Manning, 2021a). The pain can radiate anywhere in the thorax or abdomen. Unlike the classic description of the character of pain in aortic dissection as ripping or tearing, pain is more often described as sharp and less often as migratory.

Typical symptoms and signs were less common among those >70 years of age, representing almost one-third of patients (Black & Manning, 2021a). Older patients were significantly less likely to have an abrupt onset of pain compared with younger patients. The localization of pain to the abdomen was reported by 21% of patients in type A dissection and 43% of patients in type B dissection (Black & Manning, 2021a). In such patients, a high index of suspicion for mesenteric vascular compromise is warranted.

The presence of impaired or absent blood flow to peripheral vessels is termed a pulse deficit, defined as a weak or absent carotid, brachial, or femoral pulse resulting from the intimal flap or compression by hematoma (Black & Manning, 2021b). A considerable variation (>20 mmHg) in systolic blood pressure may be seen when comparing the blood pressure in the arms.

In IRAD reviews, women are less likely to have a pulse deficit than men (Black & Manning, 2021b). Compared with younger patients, older adult patients (>70 years of age) were significantly less likely to have any pulse deficit. In patients with an aortic arch or thoracoabdominal aorta involvement, pulse deficits are common and occur in 19% to 30% of patients compared with 9% to 21% with a descending aortic dissection (Black & Manning, 2021b).

In the IRAD population, the involvement of the brachiocephalic trunk was noted in 14.5% of patients, the left common carotid artery in 6.0%, the left subclavian artery in 14.5%, and the femoral arteries in 13.0% to 14.0% (Black & Manning, 2021b). Patients presenting with pulse deficits more often had neurologic deficits, coma, and hypotension. Carotid pulse deficits were strongly correlated with fatal CVAs, consistent with prior observations. The number of pulse deficits was also clearly associated with increased mortality. Within 24 hours of presentation (Black & Manning, 2021b):

• 9.4% of patients with no pulse deficits died
• 15.8% of patients with one or two deficits died
• 35.3% of patients with three or more deficits died

For isolated lower extremity pulse deficits, mortality from lower extremity ischemia or its sequelae was uncommon. Nonetheless, leg ischemia caused by acute dissection is a marker of extensive dissection and may be accompanied by other compromised vascular territories (Black & Manning, 2021b). The clinical course of the peripheral ischemia can be quite variable, and up to one-third of this group may demonstrate spontaneous resolution of their pulse deficits.

Patients with a pulse deficit have higher in-hospital complications and mortality rates than those without a pulse deficit. A rapid bedside pulse examination can provide important information in diagnosing acute aortic dissection and those at risk for complications. In a previous report of patients treated during the 1990s, those with peripheral branch obstruction had a mortality rate of 23% compared with 16% for those without obstruction (Black & Manning, 2021b).

In contrast to the IRAD findings, the presence of peripheral vascular complications did not increase mortality. This finding was thought to be due to a timelier diagnosis, prompt initiation of therapy, and the recognition of the importance and appropriate treatment of peripheral vascular complications (Black & Manning, 2021b).

Aortic dissection that propagates proximally to the initial tear can involve the aortic valve. A new diastolic murmur in association with severe acute CP is a sign of acute aortic regurgitation (Black & Manning, 2021b). Characteristically, it is a diastolic decrescendo murmur associated with wide pulse pressure, hypotension, or heart failure.

Acute aortic valve regurgitation occurs in one-half to two-thirds of ascending dissections (Black & Manning, 2021b). The murmur of aortic regurgitation related to aortic dissection is most commonly heard along the right sternal border compared with the left sternal border for aortic regurgitation due to primary aortic valve disease.

The duration of the diastolic murmur may be quite short due to rapid ventricular filling and early equilibration of aortic and left ventricular diastolic pressures. In one IRAD review, patients older than 70 years of age were significantly less likely to have a murmur of aortic regurgitation than younger patients (Black & Manning, 2021b).

Focal neurologic deficits are due to propagation of the dissection proximally or distal to the initial tear involving branch arteries or due to mass effects as the expanding aorta compresses surrounding structures. Neurological symptoms, ranging from hoarseness to paraplegia and altered mental status, occur in 18% to 30% of patients with aortic dissection (Black & Manning, 2021a).

CVA or altered consciousness can be from direct extension of the dissection into the carotid arteries or diminished carotid blood flow. Alterations of consciousness are more common in women than in men.

Acute paraplegia is from spinal cord ischemia. Spinal cord ischemia from the interruption of intercostal vessels is more common with type B aortic dissections than with type A dissections. It may occur in 2% to 3% of all patients (Black & Manning, 2021b).

Horner syndrome is from compression of the superior cervical sympathetic ganglion. 

Hoarseness is from vocal cord paralysis due to compression of the left recurrent laryngeal nerve.

Syncope, hypotension, or shock at initial presentation are more common in patients with ascending aortic dissection, whereas hypertension is more common in descending aortic dissection (Black & Manning, 2021b). Hypotension/shock may be related to rupture of the aorta or propagation of the dissection via the following mechanisms:

• Cardiac tamponade from rupture can lead to sudden death
  • Cardiac tamponade occurs more often in women than in men
• Acute aortic valve regurgitation
• Acute myocardial ischemia or MI due to coronary occlusion
  • The right coronary artery is most commonly involved and infrequently leads to complete heart block
• Hemothorax or hemoperitoneum, and possibly exsanguination if the dissection extends through the adventitia in the thoracic or abdominal aorta

According to one review, syncope accompanies 13% of dissections involving the ascending aorta (Black & Manning, 2021a). Syncope occurs in 5% to 10% of patients and often indicates the development of cardiac tamponade or involvement of the brachiocephalic vessels (Black & Manning, 2021b). Overall, patients in the IRAD study presenting with syncope were more likely to have a type A dissection than a type B dissection and more likely to have cardiac tamponade. Similarly, they were more likely to have a CVA and more likely to die in the hospital (Black & Manning, 2021b).

Although patients presenting with syncope had a higher rate of severe complications (tamponade, CVA, death), almost one-half of syncope patients had none of those, as mentioned earlier complications to explain their loss of consciousness (Black & Manning, 2021b).

The temporal pattern of presentation (acute, subacute, or chronic) (Thompson & Kabrhel, 2020):

• Acute:
  • Patients with acute PE typically develop signs and symptoms immediately after obstruction of pulmonary vessels.
• Subacute:
  • Some patients with PE may also present subacutely within days or weeks following the initial event.
• Chronic:
  • Patients with chronic PE slowly develop symptoms of pulmonary hypertension over many years (i.e., chronic thromboembolic pulmonary hypertension [CTEPH]).

The presence or absence of hemodynamic stability (hemodynamically unstable or stable) (Thompson & Kabrhel, 2020):

• Hemodynamically unstable PE is also called "massive" or "high-risk" PE. Hemodynamically unstable PE is that which results in hypotension which is defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from baseline for a period >15 minutes or hypotension that requires vasopressors or inotropic support and is not explained by other causes such as sepsis, arrhythmia, left ventricular dysfunction from acute myocardial ischemia or MI, or hypovolemia. Although hemodynamically unstable PE is often caused by large (i.e., massive) PE, it can sometimes be small in patients with underlying cardiopulmonary disease. Thus, the term "massive" PE does not necessarily describe the size of the PE as much as its hemodynamic effect (Thompson & Kabrhel, 2020).
• Hemodynamically stable PE is defined as PE that does not meet the definition of hemodynamically unstable PE. Hemodynamically stable PE is called:
  • "Submassive" or "intermediate-risk" PE if there is associated right ventricular strain, OR
  • "Low-risk" PE if there is no evidence of right ventricular strain.

There is a spectrum of severity within this population ranging from patients who present with small, mildly symptomatic, or asymptomatic PE (also known as "low-risk PE") to those who present with mild or borderline hypotension that stabilizes in response to fluid therapy or those who present with right ventricle dysfunction (also known as "submassive" or "intermediate-risk" PE).

The distinction between hemodynamically stable and unstable PE is important because patients with hemodynamically unstable PE are more likely to die from obstructive shock (i.e., severe right ventricular failure). Importantly, death from hemodynamically unstable PE often occurs within the first two hours, and the risk remains elevated for up to 72 hours after presentation (Thompson & Kabrhel, 2020).

The anatomic location lends the names saddle, lobar, segmental, and subsegmental. Saddle PE lodges at the bifurcation of the main pulmonary artery, often extending into the right and left main pulmonary arteries. Approximately 3% to 6% of patients with PE present with a saddle embolus (Thompson & Kabrhel, 2020). Traditionally, saddle PE was thought to be associated with hemodynamic instability and death. However, retrospective studies suggest that among those diagnosed with a saddle embolus, only 22% are hemodynamically unstable, with an associated mortality of 5% (Thompson & Kabrhel, 2020).

A clot "in transit" through the heart is often classified as a form of PE, even though the thrombus has not yet lodged in a pulmonary artery. Clot-in-transit is associated with high mortality (up to 40%) (Thompson & Kabrhel, 2020).

Most PEs move beyond the bifurcation of the main pulmonary artery to lodge distally in the main, lobar, segmental, or subsegmental branches of a pulmonary artery. PE can be bilateral or unilateral, depending on whether they obstruct arteries in the right, left, or both lungs. Smaller thrombi located in the peripheral segmental or subsegmental branches are more likely to cause pulmonary infarction and pleuritis.

The presence or absence of symptoms also categorizes the type of PE(Thompson & Kabrhel, 2020):

• Symptomatic PE refers to the presence of symptoms that usually leads to radiologic confirmation of PE.
• Asymptomatic PE refers to the incidental finding of PE on imaging (e.g., contrast-enhanced CT performed for another reason) in a patient without symptoms.

Estimates of the incidence of PE in the general population have increased following the introduction of D-dimer testing and CT pulmonary angiography (CTPA) in the 1990s (Thompson & Kabrhel, 2020). One database analysis reported a doubling in the incidence of PE from 62 cases per 100,000 in the five years before 1998 to 112 cases per 100,000 in the seven years after 1998 (Thompson & Kabrhel, 2020). Other studies have confirmed similarly increased rates over time.

The overall incidence is higher in males compared with females. The incidence rises with increasing age, particularly in women, such that PE has an incidence of >500 per 100,000 after the age of 75 years (Thompson & Kabrhel, 2020). The use of statins may reduce the incidence of PE.

In the U.S., PE accounts for approximately 100,000 annual deaths (Thompson & Kabrhel, 2020). However, many causes of sudden cardiac death are thought to be secondary to PE, so the actual mortality attributable to PE is difficult to estimate.

Deaths from diagnosed PE have been declining. Overall mortality from PE appears to be high. One study reported a 30-day and one-year mortality at 4% and 13%, respectively, and a case-fatality rate that increased with increasing age (Thompson & Kabrhel, 2020).

Age-adjusted mortality rates for African-American adults have been reported to be 50% higher than those for whites. Additionally, mortality rates for whites are 50% higher than those for other races (Asian, American Indian, etc.) (Thompson & Kabrhel, 2020).

• Hospitalized gynecologic patients
• Hospitalized medical patients
• Hospitalized surgical patients
• Patients with acute traumatic spinal cord injury
• Patients who are pregnant
• Patients with inherited thrombotic disorders
• Patients with malignancy
• Patients with nephrotic syndrome
• Patients with stroke
• Patients with total joint arthroplasty or replacement

The pathogenesis of PE is similar to that which underlies the generation of thrombus (i.e., Virchow's triad). Virchow's triad consists of venous stasis, endothelial injury, and a hypercoagulable state.

Risk factors for PE alone confirm that they are similar to those for VTE in general. Risk factors can be classified as inherited (i.e., genetic) and acquired. Twenty to thirty genetic risk factors for VTE have been identified, including (Hollander & Chase, 2021; Thompson & Kabrhel, 2020):

• Factor V Leiden (there is a hematologic predisposition for venous thrombosis formation)
• Prothrombin gene mutation (20210-A)
• Anatomic predisposition (e.g., thoracic outlet syndrome)

Acquired risk factors can be further sub-classified as provoking or non-provoking. Provoking risk factors include (Hollander & Chase, 2021; Thompson & Kabrhel, 2020):

• Central venous catheterization
• Patients with cancer, lung, or chronic heart disease
• Patients with a personal or family history of hypercoagulability
• Pregnancy
• Recent history of prolonged immobilization
• Long-distance travel
• Recent surgery (particularly an orthopedic procedure of the lower extremity lasting more than 30 minutes)
• Trauma
• Use of certain hormonal contraceptives or chemotherapeutic agents that raise serum levels of estrogen and, to a lesser extent, progestin.

Non-provoking risk factors include:

• Heavy cigarette smoking
• Obesity

Most emboli are thought to arise from lower extremity proximal veins (iliac, femoral, and popliteal), and more than 50% of patients with proximal DVT have concurrent PE at presentation (Hollander & Chase, 2021; Thompson & Kabrhel, 2020).

Calf vein DVT rarely embolizes to the lung, and two–thirds of calf vein thrombi resolve spontaneously after detection. However, if untreated, one-third of calf vein DVT extends into the proximal veins, where they have greater potential to embolize (Hollander & Chase, 2021; Thompson & Kabrhel, 2020).

PE can also arise from DVT in non-lower-extremity veins, including renal and upper extremity veins, although embolization from these veins is less common. Most thrombi develop at sites of decreased flow in the lower extremity veins, such as valve cusps or bifurcations. However, they may also originate in veins with the higher venous flow, including the inferior vena cava or the pelvic veins, and non-lower-extremity veins, including renal and upper extremity veins (Hollander & Chase, 2021; Thompson & Kabrhel, 2020).

Pulmonary emboli are typically multiple, with the lower lobes being involved in the majority of cases. Once the thrombus lodges in the lung, a series of pathophysiologic responses can occur (Hollander & Chase, 2021; Thompson & Kabrhel, 2020):

• Infarction:
  • In about 10% of patients, small thrombi lodge distally into the segmental and subsegmental vessels resulting in pulmonary infarction.
  • These patients are more likely to have pleuritic CP and hemoptysis, presumed to be due to an intense inflammatory response in the lung and adjacent visceral and parietal pleura.
• Abnormal gas exchange:
  • Impaired gas exchange from PE is due to the following two mechanisms which cause hypoxemia:
    • Mechanical and functional obstruction of the vascular bed altering the ventilation to perfusion ratio.
    • Inflammation resulting in surfactant dysfunction and atelectasis, resulting in functional intrapulmonary shunting.
      • Inflammation is also thought to be responsible for stimulating respiratory drive resulting in hypocapnia and respiratory alkalosis.
      • Hypercapnia and acidosis are unusual in PE unless shock is present.
• Cardiovascular compromise:
  • Hypotension from PE is due to diminished stroke volume and cardiac output.
  • In patients with PE, pulmonary vascular resistance (PVR) is increased due to physical obstruction of the vascular bed with thrombus and hypoxic vasoconstriction within the pulmonary arterial system. Increased PVR, in turn, impedes right ventricular outflow and causes right ventricular dilation and flattening or bowing of the intraventricular septum. Reduced flow from the right ventricle and right ventricular dilation reduces left ventricular preload, thereby compromising cardiac output.
    • For example, when obstruction of the pulmonary vascular bed approaches 75%, the right ventricle must generate a systolic pressure over 50 mmHg to preserve adequate pulmonary artery flow. When the right ventricle is unable to accomplish this, it fails, and hypotension ensues.
      • Thus, multiple large thrombi are generally responsible for hypotension in patients without the underlying cardiopulmonary disease via this mechanism.
      • In contrast, in patients with underlying cardiopulmonary disease, smaller emboli can induce hypotension, likely due to a substantial vasoconstrictive response and/or an inability of the right ventricle to generate sufficient pressure to combat high PVR.

A PSP is traditionally defined as a pneumothorax that presents without a precipitating external event in the absence of clinical lung disease (Lee, 2021a). Although PSP is not associated with known clinical lung disease (e.g., chronic obstructive pulmonary disease [COPD]), most affected patients have unrecognized lung abnormalities (mostly subpleural blebs) that likely predispose them to pneumothorax. However, following investigation, some patients with apparent PSP may have other more serious underlying lung diseases (e.g., Birt-Hogg-Dubé syndrome, thoracic endometriosis, lymphangioleiomyomatosis), thereby re-categorizing them as having secondary spontaneous pneumothorax (SSP). Thus, many experts believe that the distinction between pneumothorax in patients “without” lung disease (i.e., pneumothorax with subpleural blebs, also known as PSP) and pneumothorax in patients with lung diseases (i.e., SSP) is somewhat artificial and that PSP and SSP may exist on either end of a continuum.

PSP is more common in men than women (roughly three to six times higher) (Lee, 2021b). The incidence of PSP in men ranges from 7.4 per 100,000 population per year in the U.S. The incidence of PSP in women ranges from 1.2 per 100,000 population per year in the U.S..

A hospital database study of ED visits from January 2008 to December 2014 reported that 79% of pneumothoraces were males and 21% in females (Lee, 2021b). The prevalence of asymptomatic PSP is unknown, but one retrospective study of Japanese students suggested that the rate may be as high as 0.042% and higher in men than women (Lee, 2021b). Mild collapse (i.e., <10% collapse) was present in approximately half of the individuals, most of whom underwent intervention.

PSP is thought to be due to small apical subpleural blebs or bullae (i.e., air sacs between the lung tissue and pleura) that rupture into the pleural cavity. The mechanism of bleb/bulla formation is unknown. However, since PSP classically occurs in tall, thin males between the ages of 10 and 30 years, the development of subpleural blebs is thought to be due to either increasing negative pressure or greater mechanical alveolar stretch at the apex of the lungs during growth or a congenital phenomenon in which lung tissue at the apex grows more quickly than the vasculature, thereby outstripping its blood supply (Lee, 2021a).

Pathologic assessment of resected specimens suggests disrupted areas of mesothelial cells, inflammation, and pores of 10 to 20 microns in diameter rather than a breach in the visceral pleural membrane. The leakage of fluorescein seen on autofluorescence thoracoscopy also supports this theory.

Associated risk factors of tension pneumothoraxes include (Lee, 2021a):

Smoking (cigarette, cannabis):

Cigarette smoking (current or past) is a significant risk factor for PSP, probably due to airway inflammation and respiratory bronchiolitis.

In an analysis of four studies that included 505 patients with PSP, 91% were smokers (Lee, 2021a). Furthermore, the risk of PSP was directly related to the amount of cigarette smoking. Compared with nonsmokers, the relative risk of PSP in men was seven times higher in light smokers (1 to 12 cigarettes per day), 21 times higher in moderate smokers (13 to 22 cigarettes per day), and 102 times higher in heavy smokers (>22 cigarettes per day). The relative risk was 4, 14, and 68 times higher for women in light, moderate, and heavy smokers, respectively (Lee, 2021a). Similarly, patients with PSP who smoke cigarettes have more respiratory bronchiolitis and higher recurrence rates than those who do not smoke. Regularly smoking cannabis appears to increase the risk of PSP similarly.

Genetic Predisposition:

Reports have been published describing the clustering of PSP in certain families. Autosomal dominant, autosomal recessive, polygenic, and X-linked recessive inheritance mechanisms have all been proposed (Lee, 2021a).

Genetic variants associated with PSP include:

• Alpha-1 antitrypsin (M1M2 mutations)
• Fibrillin 1 (FBN1) mutations
• Human leukocyte antigen (HLA) haplotype A2B40

The autosomal dominant Birt-Hogg-Dubé syndrome (BHD) due to mutations in the folliculin [FLCN] gene [especially c.1300G>C, c.250-2A>G], hyperhomocysteinemia, alpha-1 antitrypsin, and Marfan syndrome are also inherited conditions associated with pneumothorax that may masquerade as PSP when the diagnosis is not known. For example, one study reported that 5% to 10% of patients with PSP turned out to have BHD following an investigation (Lee, 2021a).

Several reports suggest that drops in atmospheric pressure may be associated with an increase in the incidence of pneumothorax. Activities such as SCUBA diving can precipitate a spontaneous pneumothorax, and air travel may precipitate recurrence in patients with an incompletely healed pneumothorax.

SSP is defined as pneumothorax that presents as a complication of underlying lung disease. SSP has a male preponderance, but SSP presents in older patients (>55 years) in contrast with PSP. One large hospital database of admissions reported that the rate of admissions for SSP, 61% of which were due to chronic obstructive pulmonary disease (COPD), has increased by 9% over 48 years from 1968 through 2016 (Lee, 2021a). Rates were higher in males than females.

SSP occurs most frequently in patients with COPD, cystic fibrosis (CF), and asthma. Regardless of etiology, the accumulation of air in the pleural space can lead to tension pneumothorax with compression of the mediastinum, causing rapid clinical deterioration and death if unrecognized.

Nearly every lung disease can be complicated by SSP, although the most commonly associated diseases are COPD and Tuberculosis (TB) in endemic areas. In one study of hospital admissions, up to 80% of SSP cases were due to Emphysema/COPD or Interstitial lung disease (Lee, 2021a).

Other causes of SSP include:

• CF
• Necrotizing pneumonia
• Primary or metastatic lung malignancy
• Sarcoidosis

Pneumothorax typically presents as a complication of these common lung diseases and is rarely an initial manifestation. In contrast, pneumothorax may be the presenting feature of uncommon causes of SSP and the diagnosis may not be known upon presentation (e.g., lymphangioleiomyomatosis, BHD syndrome, etc.).

COPD/Emphysema:

COPD is the most common cause of SSP, with 50% to 70% of SSP cases attributed to COPD in small case series. Rupture of apical blebs or bullae is the usual cause. Patients with COPD may also be at higher risk for iatrogenic pneumothorax (e.g., venous catheterization, mechanical ventilation), particularly when there is a significant amount of underlying emphysema or air trapping. The severity of COPD correlates with the likelihood of developing SSP (Lee, 2021a).

Cystic Fibrosis (CF):

Approximately 3% to 4% of patients with CF will have an episode of SSP during their lifetime, but in those who survive to age 18, the incidence is 16% to 20% (Lee, 2021a). CF-related SSP is usually due to the rupture of apical subpleural cysts. The risk of pneumothorax in CF increases with the severity of lung function abnormalities. Other than cysts and fibrosis, other factors that may predispose to the development of pneumothorax in CF, which may reflect disease severity rather than being independent risk factors, include (Lee, 2021a):

• A prior episode of massive hemoptysis
• Infection with Aspergillus species
• Infection with Burkholderia cepacia complex
• Infection with Pseudomonas aeruginosa
• Noninvasive positive pressure
• Possibly inhaled medications

Lung Malignancy:

Both primary and metastatic lung malignancy has been associated with SSP. Among 168 patients with SSP, malignancy was the underlying cause in 16% (Lee, 2021a). The underlying malignancy was more commonly a lung primary than metastatic disease. Potential mechanisms include tumor necrosis, endobronchial obstruction with air trapping, development of necrotizing cysts or pneumonia, and coexisting COPD/emphysema.

Less commonly, malignancies that metastasize to the lung are associated with the development of necrotic cysts, which can result in SSP. Examples include (Lee, 2021a):

• Angiosarcoma
• Gastrointestinal adenocarcinoma
• Genitourinary adenocarcinoma
• Lymphoma
• Mesenchymal cystic hamartoma
• Pleuropulmonary blastoma
• Sarcoma

Necrotizing Lung Infections:

SSP can complicate the course of necrotizing pneumonia due to Pneumocystis jirovecii (i.e., pneumocystis pneumonitis [PCP]), TB, bacteria, and less often fungi or other microorganisms, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Lee, 2021a). The relative frequency of these etiologies depends upon the frequency of these diseases in the population studied. The presumed common mechanism underlying pneumothorax in patients with lung infection is direct invasion and necrosis of lung tissue, including the pleura by the microorganism itself.

Pneumocystis jirovecii:

Unilateral and bilateral SSP can be seen in patients with PCP, most often in human immune deficiency virus (HIV) patients. In the era of antiretroviral therapy (ART), the frequency of pneumothorax complicating PCP is approximately 5% to 10% (Lee, 2021a). However, another study reported lower rates, with pneumothorax complicating only 1.2% of all hospital admissions in a cohort of 599 HIV-infected patients. However, over half had non-pulmonary reasons for admission.

In patients with HIV-related PCP, it has been hypothesized that the administration of aerosolized pentamidine may increase the likelihood for PCP to grow and cause cavitation in the peripheral parts of the upper lobe, thereby increasing the risk for pneumothorax (Lee, 2021a). This phenomenon may relate to the preferential delivery of the aerosolized agent to the proximal parenchyma of the lower lobes rather than the upper lobes. Unlike bacterial pneumonia, pneumothorax associated with PCP is more likely to be bilateral than unilateral.

Bacterial Pneumonia:

SSP has been associated with bacterial pneumonia caused by Staphylococcus, Klebsiella, Pseudomonas, Streptococcus pneumoniae, and anaerobic organisms. Among 168 patients with SSP, bacterial pneumonia was the etiology in 11% of cases (Lee, 2021a). SSP in bacterial pneumonia is more likely to be unilateral than bilateral. It can be associated with an extension of bacterial infection into the pleura and the development of empyema, giving the appearance of a hydropneumothorax.

Tuberculosis (TB):

SSP occurs in 1% to 3% of patients hospitalized with pulmonary TB (Lee, 2021a). Rates are higher in endemic areas. The pneumothorax is usually due to the rupture of a tuberculous cavity into the pleural space.

Other pulmonary infections have been associated with pneumothorax, including fungal, viral, and mycobacterial infections other than TB.

Cystic Lung Disorders:

Pneumothorax is common in lung conditions associated with cysts. However, since many of these conditions are rare, pneumothorax in this setting may masquerade as PSP when the underlying diagnosis is unknown. Disorders associated with cysts include conditions such as (Lee, 2021a):

• BHD syndrome
• Diffuse Langerhans cell histiocytosis
• Lymphangioleiomyomatosis
• Lymphocytic interstitial pneumonitis (e.g., Sjögren syndrome)

Catamenial Pneumothorax:

Catamenial pneumothorax refers to a pneumothorax occurring in association with menses due to thoracic endometriosis. Young females with endometriosis may experience menses-related pneumothoraces if pleural involvement exists. CP or hemoptysis perimenstrually in a young woman with or without a history of endometriosis might suggest catamenial pneumothorax (Lee, 2021a). In this condition, pneumothorax is thought to relate to the development and involution of pleural implants comprised of endometrial tissue. Consequently, some experts consider this PSP since parenchymal lung disease is typically absent.

HIV:

Pneumothorax is seen in HIV due to several etiologies, particularly infections including (Lee, 2021a):

• Bacterial pneumonia
• Fungal, viral, and mycobacterial infections
• PCP pneumonia
• Pulmonary TB
• Toxoplasmosis

Patients with HIV can also be at risk for iatrogenic pneumothorax and pneumothorax due to the presence of pneumatoceles (typically from old Staphylococcal or PCP infection), Kaposi sarcoma, intravenous drug abuse, and cigarette smoking. One report suggested that the degree of immunosuppression in HIV may affect the etiology of pneumothorax. In patients with CD4 positive lymphocyte counts >200 cells/mL, pneumothorax was more likely due to bacterial pneumonia, whereas pneumothorax was more often associated with those with counts <200 cells/mL Pneumocystis jirovecii (Lee, 2021a).

Architectural Abnormalities of the Pleural Membrane:

Pneumothorax may occur in conditions where the pleural membrane's integrity and parenchyma are abnormal, the diagnosis of which may or may not be known at the time of presentation. These include (Lee, 2021a):

• Ehlers-Danlos syndrome
• Homocystinuria
• Marfan syndrome

In Marfan and Ehlers-Danlos syndrome, it is thought that abnormal elastin or collagen content of the pleural membrane and parenchyma may predispose patients to pneumothorax (Lee, 2021a). Why patients with homocystinuria develop pneumothorax is less clear, but homocysteine plays a role in vascular homeostasis and smooth muscle and collagen production regulation in the lung. Patients with Marfan syndrome may also develop parenchymal cysts that may increase the risk of developing a pneumothorax.

Other less common causes of SSP include:

• Ankylosing spondylitis
• Asthma
• Granulomatous lung diseases (e.g., rheumatoid arthritis, granulomatosis with polyangiitis, and sarcoidosis)
• Inhalation of cocaine
• Interstitial lung disease (e.g., idiopathic pulmonary fibrosis, silicosis)
• Several case series have also described pneumothorax occurring in patients with coronavirus disease 2019 (COVID-19) without noninvasive or invasive ventilation.

Pneumothorax is traumatic when due to blunt or, more commonly, penetrating thoracic trauma. Trauma is probably the most common cause of pneumothorax.

Traumatic pneumothorax can be categorized as iatrogenic or non-iatrogenic (Lee, 2021a):

Iatrogenic:

Pneumothorax is iatrogenic when induced by a medical procedure, typically procedures that can introduce air into the pleural space via the chest, neck, gut, or abdomen. These include:

• Breast tissue expander placement
• Chest acupuncture
• Colonoscopy
• Mechanical ventilation
• Pacemaker insertion
• Shoulder arthroscopy
• Thoracentesis
• Thoracic or esophageal procedures or surgery
• Tracheostomy

Most commonly, iatrogenic pneumothorax is induced by lung procedures (e.g., percutaneous or transbronchial lung or mediastinal biopsy and fiducial seed placement for radiotherapy, thoracentesis) central venous catheterization.

The prevalence of iatrogenic pneumothorax is poorly studied but likely varies with operator experience, presence of risk factors such as underlying lung disease, and prevalence of procedures performed. In one study of over 12,000 procedures, the prevalence of pneumothorax was 1.4%, among which 57% were due to emergency procedures (Lee, 2021a).

The most frequent procedures associated with pneumothorax were central venous catheterization, thoracentesis, and barotrauma due to mechanical ventilation. Another study reported a higher incidence of iatrogenic pneumothorax in teaching compared with non-teaching hospitals (Lee, 2021a).

Non-Iatrogenic:

Non-iatrogenic pneumothorax due to external trauma may be minor or severe. It is also termed “open pneumothorax” when a penetrating traumatic chest wall defect is present, through which atmospheric air enters the pleural space during inspiration (i.e., "sucking wound") and exits during expiration, resulting in a mediastinal swing away from the affected side during inspiration and toward the affected side during expiration (“mediastinal flutter”) (Lee, 2021a).

Several rare case reports have described pneumothorax in association with the following (Lee, 2021a):

Anorexia Nervosa:

Patients with anorexia nervosa may develop spontaneous pneumothorax.

It is thought that the pulmonary parenchymal consequences of malnutrition (e.g., emphysema) contribute to the development of pneumothorax in these patients, but other unknown processes may be at play.

Exercise, Illicit Drug Use, Immunosuppressant Drugs:

Rare case reports and anecdotes suggest a possible relationship between pneumothorax and exercise, drug abuse (e.g., cocaine or heroin), or chemotherapeutic drugs (Lee, 2021a). It has been postulated that exercise and illicit drug use may cause pneumothorax, leading to deeper inhalation and Valsalva maneuvers. Some injection drug users may also develop traumatic pneumothorax from attempting to inject into the neck veins. A detailed drug history or track marks may suggest illicit drug use or identify immunosuppressant drugs not previously suspected as an etiology of pneumothorax.

Air Travel and Scuba Diving:

Pneumothorax may be associated with air travel and diving, although an underlying lung disorder may increase this risk further.

Pneumothorax most often presents with sudden onset of dyspnea and pleuritic CP. Since pneumothorax is usually unilateral, the pain is usually felt on the ipsilateral side but may be central or bilateral in rare cases when the pneumothorax is bilateral (Lee, 2021a).

The intensity of dyspnea can range from mild to severe. The severity of the symptoms primarily relates to the volume of air in the pleural space and the degree of pulmonary reserve, with dyspnea being more prominent if the pneumothorax is large or underlying disease is present.

Pneumothorax can present at all ages. Patients with primary spontaneous pneumothorax (PSP, i.e., associated with subpleural blebs in the absence of an underlying disorder) are typically in their early 20s (Lee, 2021a). PSP is rare after age 40 and classically occurs in young, tall, thin, smoking males. In contrast, since most cases of SSP (i.e., that associated with underlying lung disease) are due to emphysema, these patients tend to be older. However, this finding is not absolute. For example, pneumothorax in patients with lymphangioleiomyomatosis or thoracic endometriosis presents in young, non-smoking females of reproductive age.

Symptoms usually develop when the patient is at rest, although occasionally, pneumothorax develops during exercise, air travel, scuba diving, or illicit drug use. Alternatively, symptoms may occur during or following an invasive procedure or trauma to the chest, neck, gut, or abdomen.

A history of a risk factor or a disorder that can be complicated by pneumothorax may be present as well.

In patients with a small pneumothorax, physical examination findings may not be evident or may be limited to signs of the underlying lung disease, if present. However, characteristic physical findings when a large pneumothorax is a present include (Lee, 2021a):

• Absent tactile or vocal fremitus
• Decreased chest excursion on the affected side
• Diminished breath sounds
• Enlarged hemithorax on the affected side
• Hyper-resonant percussion
• Subcutaneous emphysema (rare)

Characteristic physical findings of a sizeable pneumothorax or a pneumothorax in a patient with significant underlying lung disease include (Lee, 2021a):

• Accessory muscle use
• A history of hypercapnia
• A pulse oxygen saturation <92%
• Tachypnea

Tracheal deviation away from the affected side is a late sign but does not always indicate tension pneumothorax. Hemodynamic compromise (e.g., tachycardia, hypotension) is an ominous sign and suggests a tension pneumothorax or impending cardiopulmonary collapse. Some patients with mild or chronic pneumothorax may be asymptomatic and discovered incidentally.

A joint and skin examination may reveal (Lee, 2021a):

• Dry eye and joint disease suggestive of Sjögren syndrome (which can be complicated by lung cysts)
• Joint hypermobility or hyperextensible skin consistent with Ehlers Danlos syndrome
• Pectus carinatum and disproportionate tall stature suggestive of Marfan syndrome

• Venous return is normally bimodal, with peaks during ventricular systole and early diastole.
• The effusion produces compression throughout the cardiac cycle, with cardiac volume becoming minimal during ejection. Consequently, as cardiac tamponade becomes more severe, venous return is progressively shifted to systole as the peak associated with early diastolic filling diminishes.
• When cardiac tamponade is very severe, the total venous return falls, the cardiac chambers shrink, and cardiac output and blood pressure fall.

• The inspiratory decline in thoracic pressure is transmitted through the pericardium to the right side of the heart and the pulmonary vasculature. Consequently, systemic venous return to the right heart increases with inspiration, and pulmonary venous return to the left heart decreases.
• In cardiac tamponade, the rigid pericardium prevents the free wall from expanding. The ensuing distension of the right ventricle is limited to the interventricular septum, which along with relative underfilling of the left ventricle, causes the septum to bulge to the left, reducing left ventricular compliance and contributing to further decreased filling of the left ventricle during inspiration. This concept is referred to as "ventricular interaction" or "ventricular interdependence."
  • These changes will occur once pericardial pressure becomes substantially higher than ventricular diastolic pressures.
  • In less severe diseases, however, the degree to which they occur is related in part to the rate of pericardial fluid accumulation and pericardial compliance, both of which are related to the underlying cause.

(e.g., trauma) into a relatively stiff pericardium can rapidly lead to cardiac tamponade.

• As intrapericardial volume increases, an initial small increase in intrapericardial pressure is followed by an almost vertical ascent.

By comparison, chronic accumulation of a pericardial effusion (e.g., due to renal failure or malignancy) allows the pericardial compliance to increase gradually. As a result, intrapericardial pressure increases more slowly until a critical point is reached when an almost vertical ascent is again seen. In this setting, cardiac tamponade may not occur until two liters or more have accumulated. Very little fluid needs to accumulate to produce cardiac tamponade once the pericardium can no longer stretch. At this point, the initial removal of fluid during pericardiocentesis produces the largest reduction in intrapericardial pressure.

Occurs within minutes due to (Hoit, 2021):

• Complications of an invasive diagnostic or therapeutic procedure
  • Rupture of the heart or aorta
  • Trauma

Acute cardiac tamponade generally results in a picture resembling cardiogenic shock requiring urgent pericardial pressure. Acute cardiac tamponade is sudden in onset, may be associated with CP, tachypnea, and dyspnea, and is life-threatening if not promptly treated. The jugular venous pressure is markedly elevated and may be associated with venous distension in the forehead and scalp. The heart sounds are often muted.

Hypotension is common due to the decline in cardiac output. Patients in cardiogenic shock typically have (Hoit, 2021):

• Cool extremities
• Decreased urine output
• Peripheral cyanosis

Usually is a less dramatic process than acute cardiac tamponade. Subacute cardiac tamponade occurs over days to weeks and can be associated with neoplastic, uremic, or idiopathic pericarditis (Hoit, 2021). Patients may be asymptomatic early in the course, but once intrapericardial pressure reaches a critical value, they complain of (Hoit, 2021):

• Chest discomfort or fullness
• Dyspnea
• Fatigability
• Peripheral edema

The physical examination in subacute severe cardiac tamponade may reveal hypotension with narrow pulse pressure, reflecting the limited stroke volume. However, patients with preexisting HTN may remain hypertensive due to increased sympathetic activity in the setting of cardiac tamponade.

Low pressure (occult) cardiac tamponade is a subset of subacute cardiac tamponade and occurs in severely hypovolemic patients. Patients who are severely hypovolemic because of traumatic hemorrhage, hemodialysis, or ultrafiltration, or over diuresis at presentation may have a low-pressure cardiac tamponade in which the intracardiac and pericardial are present diastolic pressures are low (Hoit, 2021).

The hemodynamic significance of these effusions can be demonstrated on echocardiography by right heart chamber collapse and respiratory variations in transvalvular flows. A fluid challenge with a rapid infusion of one liter of isotonic saline in the catheterization laboratory will usually elicit typical cardiac tamponade hemodynamics. Clinical findings commonly associated with cardiac tamponade (e.g., tachycardia, jugular venous distention, and pulsus paradoxus) were significantly less common in low-pressure cardiac tamponade than in classic cardiac tamponade.

Regional cardiac tamponade occurs when a loculated, eccentric effusion or localized hematoma produces regional cardiac tamponade in which only selected chambers are compressed (Hoit, 2021). Consequently, the typical physical, hemodynamic, and echocardiographic signs of cardiac tamponade, including pulsus paradoxus, diastolic pressure equalization, and chamber compression in standard apical and parasternal views, may be absent or attenuated.

Regional cardiac tamponade is most often seen after pericardiotomy or MI. Clinical suspicion should be heightened in these settings. Establishing the diagnosis is challenging and may require additional echocardiographic views (e.g., subcostal or transesophageal) and other advanced imaging techniques (e.g., computed tomography) (Hoit, 2021).