Prinzmetal angina I20.1

The syndrome of Prinzmetal angina was first described in 1959 by Myron Prinzmetal et al. (Kasper 2015).

A description of the clinical features including ECG changes and angiographic findings is found in 1978 by A. Maserati et al. The results showed that vasopastic angina (VSA) is much more polymorphic than Prinzmetal had assumed at the time (Wang 2018).

VSA is a syndrome that occurs predominantly at rest and is characterized by

• Severe cardiac pain
• ischemia of the myocardium
• temporary changes of the ST- track (Pinger 2019)

Prinzmetal angina belongs to the group of unstable angina pectoris (Barmeyer 2010).

In the literature, there are different indications of the occurrence of vasospastic angina (VSA). According to (Keller 2004) mainly young women without a classic risk profile for coronary heart disease - with the exception of smoking - are affected. Stierle (2017) speaks of a balanced gender ratio.

The incidence of VSA is 3 times higher in Japanese than in Caucasian patients (Wang 2018). Basically, it can be said that the disease occurs predominantly in heavy smokers and in patients who are younger than the usual CHD patients (Stierle 2017). The prevalence of VSA has decreased significantly in the last decades. The cause has not yet been proven (Kasper 2015).

Associated non-cardiac diseases:

• Migraine in up to 25
• Raynaud's syndrome at about 33 % (Stierle 2017)

VSA involves a focal spasm of a coronary artery that causes severe transient ischemia of the myocardium. The exact pathophysiological mechanism is not understood. Hypercontractility of the smooth vascular muscles in the coronary artery area is suspected to be caused by adrenergic vasoconstriction, leukotrienes or serotonin (Kasper 2015).

Triggers of a VSA can be (de Luna 2014):

• nicotine
• Cocaine
• Hyperventilation
• Hypomagnesemia
• Amphetamines
• Electrolyte disorders
• Cold provocation
• Autoimmune diseases

less often with:

• Alcohol Withdrawal
• mental disorders (Stierle 2017)
• triggered by different drugs such as:
• calcium channel blockers, etc. (Picard 2019)

The symptoms are similar to those of angina pectoris with

• retrosternal localized pain often with radiation in
  • the neck / nape of the neck
  • Lower jaw
  • Teeth
  • Shoulder area
  • both (!) arms (with focus on the ulnar sides of the forearms), which can radiate into the ulnar fingertips
• Pain in the epigastrium (rarely also below the navel)
• typically the region of the trapezius muscle remains painless (pain in this area is typical of pericarditis) (Kasper 2015).

The pain occurs at rest, is very severe and often accompanied by a (presumably rhythmogenic) syncope. Occurrence under stress is possible, but then signs of accompanying arteriosclerosis of the coronary arteries (Stierle 2017).

There is a circadian variability between midnight and about 8.00 a.m. The attacks can occur cluster-like or sporadically (Pinger 2019).

Heart catheter: The provocation of a VSA is possible with different stimuli. According to ESC 2013 there is a IIa- indication for coronary angiographic detection of induced focal spasms.

The following stimuli are used:

• Acetylcholine i. c. up to 200 µg for the ramus interventricularis anterior, then 80 µg for the A. coronaria dexter. The largest study involving 283 patients showed epicardial spasms in 33.4%, microvascular spasms in 24.2%, no clear test result in 28.6% and an inconspicuous test result in 13.8% (Ong 2014).
• alternatively also by Ergonovin i. c. up to 60 µg (here a positive result is not so often found)(Pinger 2019)
• Histamine (de Luna 2014)
• Hyperventilation with 30 breaths/min. for 5 minutes (if specificity is sufficient, sensitivity is significantly lower) (Pinger 2019)

Even if the symptoms are clear, coronary angiography should always be performed with the above-mentioned provocation test. Typically, 2/3 of the patients have a low to pronounced coronary arteriosclerosis, 1/3 have no coronary arteriosclerosis before the provocation test (Stierle 2017). A temporary coronary spasm is found under the provocation. This occurs in already existing plaques within 1 cm around a plaque. The most frequent occurrence of spasm is in the A. coronary dextra. Often several sites of an artery are affected or several arteries are affected simultaneously (Kasper 2015).

Typically, there is NO increase in troponin, neither in troponin I nor in troponin T. A small CK- MB- increase is possible (Kasper 2015).

In younger patients with angina pectoris at rest who do not respond to treatment with beta blockers, the possibility of Prinzmetal angina should always be considered. (Stierle 2017).

Inspection and auscultation: The cardiac findings are usually unremarkable (Kasper 2015).

ECG: There are not necessarily ECG changes with VSA. In about 50 % of the patients there are typical pointed, symmetrical T-waves, which can be accompanied by ST- elevation. Negative T-waves occur in about 20 %. Ventricular arrhythmias are very common. These can be life-threatening (de Luna 2014).

Long-term ECG: As the ECG changes are variable, the long-term ECG is used to detect a lowering of the ST segment (Stierle 2017). There is a IIa- indication for this (Pinger 2019).

Exercise ECG: An ergometry is unspecific for VSA and therefore not meaningful (Stierle 2017). It is found with approx. 1/3 of each case a:

• inconspicuous finding
• ST-sinkages
• ST lifts (Pinger 2019)

Since VSA typically occurs at rest, the differential diagnosis must be distinguished between:

• Acute coronary syndrome
  • unstable angina pectoris
  • ST elevation myocardial infarction(STEMI)
  • non-ST elevation myocardial infarction(NSTEMI) (Herold 2020)
  • Kounis syndrome (rare)

The so-called "big five" of chest pain are:

1. Acute coronary syndrome
2. Pulmonary embolism
3. Aortic dissection
4. Boerhaave syndrome (spontaneous rupture of the esophagus after severe vomiting)
5. Tension pneumothorax (Herold 2020)

Patients should be educated about the mandatory need to stop smoking (Stierle 2017).

The treatment consists of a drug therapy with:

Calcium channel blocker: The cornerstones of the treatment are calcium channel blockers. They can be used to achieve a better prophylaxis of seizures than nitrates (Stierle 2017).

In an observational study, a possible survival advantage was found by treatment with calcium channel blockers (Pinger 2019).

The calcium channel blockers are all effective with varying degrees of effectiveness. Some authors speak of 90 % efficacy, others of about 1/3 of the patients becoming completely symptom-free in the long term (Pinger 2019).

The treatment should be continued for at least 6 - 12 months. If the patient is free of symptoms, a slow creeping out can be tried. If the symptoms reoccur in the further course of the disease, a therapy of several years is recommended before a renewed creeping out is possible (Stierle 2017).

Even after the occurrence of a myocardial infarctionor ventricular fibrillation, several years of treatment are necessary before an attempt to expel the patient is possible (Stierle 2017).

Recommended dosage for calcium channel blocker:

The maximum tolerated dose should be administered, e.g.

• Diltiazem 120 mg - 360 mg
• Verapamil 240 mg - 480 mg
• Nifedipine 60 mg - 120 mg

If a substance proves to be ineffective, it is recommended to switch to another preparation or a combination of 2 or 3 calcium channel blockers plus the administration of a nitrate (Pinger 2019).

Recommended dosage for parenteral emergency therapy:

• Diltiazem 0.3 mg/kg bw initial slow i.v. administration
• then via a perfusor with 50 ml / 100 mg, approx. 5 ml - 10 ml/h = 10 mg - 20 mg/h depending on RR (dosage: 0.0028 - 0.014 mg/kg bw/min.) (Stierle 2017)

Nitrates: Nitrates can terminate angina pectoris attacks within minutes. As long-acting preparations - in combination with Ca-blockers - they are also prophylactically effective (Pinger 2019). However, nitrates have proven to be less effective than CA blockers.

Recommended dosage for nitrates:

• ISMN 3 x 20 mg/d

or as acute therapy:

• Nitroperfusor 3 mg - 5 mg/h (Stierle 2017)

Acetylsalicylic acid: Treatment with acetylsalicylic acid is not recommended as it can increase the tendency to spasm (Pinger 2019).

Magnesium: A positive effect is described by magnesium p. o. In case of a seizure it should be administered intravenously (Stierle 2017).

Alpha-receptor blockers: Positive results have also been reported in individual cases from alpha blockers such as prazosin and clonidine (Stierle 2017).

Beta-blockers: The administration of beta-blockers often causes an increased tendency to spasm. Therefore, treatment with beta blockers should be avoided in PC patients. They may be helpful in patients with vasospasm who have coronary artery disease with fixed stenosis (Pinger 2019).

Statins: The clinical effect of statins is unclear, but a reduction of vasoconstriction is described (Pinger 2019).

Prevention of arrhythmia: In case of ischemia-induced arrhythmias or survived sudden cardiac death, an implantable cardioverter defibrillator is indicated (Stierle 2017).

In the course of a VSA, myocardial infarction may occur in rare cases. Frequent are (ventricular) arrhythmias, but these rarely ignore ventricular fibrillation or sudden cardiac death (de Luna 2014). The prognosis depends primarily on additional coronary heart disease. Without CHD, survival rates are good:

• 5-year survival rate is > 90% (Stierle 2017)

With existing insignificant CHD, the:

• annual death rate from cardiovascular events is 0.5% (Stierle 2017)

A worse prognosis is found in patients with:

• ST- elevations in several leads
• Currently in ventricular fibrillation / flutter
• C. M. Myocardial infarction

Here, sudden cardiac death can occur in up to 10% of patients (Stierle 2017).

The prognostic risk can be estimated with the help of the JCSA (Japanese Coronary Spasm Association) score(Takagi 2014).

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