Takotsubo cardiomyopathy

A 64 year old female with a history of hypertension presents with sudden onset chest pain and shortness of breath for 1 hour. She reports recent severe emotional stress due to her husband’s terminal illness. Vital signs show blood pressure 100/60 mmHg, pulse 106/min, and oxygen saturation 92% on room air. Laboratory studies reveal mild elevation of troponins. ECG shows ST segment elevation. Echocardiography demonstrates apical ballooning with hypercontractile basal segments. Coronary angiography shows no obstructive coronary artery disease. Diagnosis?

Diagnosis is Takotsubo cardiomyopathy.

1. Definition

Takotsubo cardiomyopathy is a transient non ischemic cardiomyopathy characterized by reversible regional left ventricular systolic dysfunction that mimics acute myocardial infarction but occurs without obstructive coronary artery disease.

2. Epidemiology

1. Accounts for approximately 1 to 2 percent of suspected acute coronary syndrome cases
2. Predominantly affects postmenopausal women
3. Mean age is around 60 to 70 years

3. Pathophysiology

1. Triggered by emotional or physical stress
2. Leads to catecholamine surge
3. Mechanisms include:
• Direct catecholamine mediated myocardial toxicity
• Microvascular dysfunction
• Coronary vasospasm
4. Results in regional wall motion abnormalities extending beyond a single coronary territory

4. Clinical Features

1. Chest pain and dyspnea are most common
2. May also present with:
• Syncope
• Arrhythmias
• Heart failure
• Cardiogenic shock

5. Diagnosis

5.1 Laboratory

1. Mild elevation of troponins that is disproportionate to ECG changes
2. Elevated BNP is common

5.2 ECG

1. ST segment elevation initially
2. Followed by T wave inversion

5.3 Echocardiography

1. Apical ballooning
2. Hypokinesis or akinesis of apical and mid segments
3. Hypercontractile basal segments
4. Reduced left ventricular ejection fraction

5.4 Coronary Angiography

1. No significant coronary artery obstruction
2. Required to exclude acute coronary syndrome

5.5 Cardiac MRI

1. Demonstrates myocardial edema
2. Helps exclude myocarditis
3. Shows absence of infarction pattern

6. Diagnostic Criteria (Mayo Clinic)

1. Transient regional wall motion abnormalities beyond a single vascular territory
2. Absence of obstructive coronary artery disease
3. New ECG changes or modest troponin elevation
4. Absence of pheochromocytoma and myocarditis

7. Management

7.1 Initial Approach

1. Treat as acute coronary syndrome until excluded

7.2 Stable Patients

1. Beta blockers
2. ACE inhibitors or ARBs
3. Diuretics if heart failure present
4. Continue therapy for 3 to 6 months with follow up imaging

7.3 Complications

1. Anticoagulation if left ventricular thrombus present
2. Manage cardiogenic shock based on presence or absence of left ventricular outflow tract obstruction

8. Complications

1. Heart failure
2. Arrhythmias
3. Left ventricular outflow tract obstruction
4. Thromboembolism
5. Cardiogenic shock

9. Prognosis

1. Usually reversible with recovery in weeks to months
2. Mortality ranges from 0 to 8 percent
3. Recurrence occurs in approximately 5 percent

10. Key Clinical Insight

Acute coronary syndrome like presentation + emotional stress + apical ballooning + normal coronary arteries = Takotsubo cardiomyopathy

11. Exam Level Pearls

1. Mimics myocardial infarction but no coronary obstruction
2. Troponin elevation is modest compared to ECG findings
3. BNP elevation is often marked
4. Apical ballooning is the classic finding
5. Most common in postmenopausal women
6. Diagnosis requires coronary angiography
7. Wall motion abnormalities extend beyond one vascular territory

Pheochromocytoma

A 30 year old male with a history of poorly controlled hypertension presents with recurrent episodes of palpitations, severe headache, and profuse sweating over several months. These episodes are sudden in onset, last for minutes, and resolve spontaneously. He also reports anxiety and a sense of impending doom during episodes. On examination, blood pressure is 160/100 mmHg and pulse is 140/min. Laboratory evaluation shows elevated 24 hour urinary fractionated metanephrines. CT scan reveals a right adrenal mass. Diagnosis?

Diagnosis is Pheochromocytoma.

1. Definition

Pheochromocytoma is a catecholamine secreting tumor arising from chromaffin cells of the adrenal medulla. Tumors arising from extra-adrenal chromaffin tissue are called paragangliomas.

2. Etiology

1. Sporadic cases are most common
2. Approximately 30 to 40 percent are hereditary

Associated syndromes include:

1. Multiple endocrine neoplasia type 2 (MEN 2)
2. Von Hippel Lindau syndrome (VHL)
3. Neurofibromatosis type 1 (NF1)
4. Hereditary paraganglioma syndromes (SDH mutations)

3. Pathophysiology

1. Excess secretion of catecholamines
• Norepinephrine causes sustained hypertension
• Epinephrine causes tachycardia, anxiety, and paroxysmal symptoms
2. Catecholamines are metabolized into metanephrines
3. Metanephrines have a longer half-life and are preferred for diagnosis

4. Clinical Features

4.1 Classic Presentation

1. Paroxysmal or sustained hypertension
2. Triad:
• Headache
• Diaphoresis
• Palpitations

4.2 Other Features

1. Tachycardia
2. Anxiety or panic attacks
3. Pallor
4. Weight loss
5. Orthostatic hypotension

4.3 Precipitating Factors

1. Stress
2. Surgery or anesthesia
3. Drugs such as:
• Tricyclic antidepressants
• Metoclopramide
• Glucocorticoids
4. Contrast agents

5. Types

1. Adrenal pheochromocytoma
• Most common
• Secretes epinephrine and norepinephrine
2. Paraganglioma
• Extra-adrenal
• Commonly secretes norepinephrine

6. Diagnosis

6.1 Biochemical Testing

1. Plasma free metanephrines is the most sensitive test
2. 24 hour urinary fractionated metanephrines
3. Preferred over catecholamines due to higher diagnostic accuracy

6.2 Imaging

1. CT abdomen and pelvis after biochemical confirmation
2. MRI if CT contraindicated
3. 123I MIBG scan for localization or metastatic disease
4. PET scan in selected cases

7. Management

7.1 Preoperative Medical Management

1. Alpha adrenergic blockade first
• Phenoxybenzamine or selective alpha-1 blockers
2. Beta blockers only after alpha blockade
• Prevent unopposed alpha stimulation
3. Volume expansion
• High sodium diet and fluids

7.2 Definitive Treatment

1. Surgical resection (adrenalectomy)

8. Complications

1. Hypertensive crisis
2. Arrhythmias
3. Myocardial infarction
4. Stroke
5. Catecholamine induced cardiomyopathy

9. Key Clinical Insight

Episodic headache + sweating + palpitations + resistant hypertension + elevated metanephrines + adrenal mass = Pheochromocytoma

10. Exam Level Pearls

1. Plasma free metanephrines are most sensitive
2. Alpha blockade must precede beta blockade
3. 30 to 40 percent cases are hereditary
4. Paragangliomas are extra adrenal tumors
5. Biopsy is contraindicated due to risk of catecholamine crisis
6. MEN 2 includes pheochromocytoma and medullary thyroid carcinoma
7. Rule of 10s is outdated

Polycythemia vera

A 55 year old male presents to his primary care physician with persistent headaches, dizziness, and episodic blurred vision over the past few months. He also reports a burning sensation in his hands and feet and generalized pruritus after hot showers. On examination, splenomegaly is noted. Vital signs show blood pressure 140/90 mmHg. Laboratory studies reveal hemoglobin 20 g/dL, hematocrit 56 percent, leukocytosis, and thrombocytosis. Serum erythropoietin is low. Bone marrow biopsy shows hypercellularity with trilineage proliferation (panmyelosis). Molecular testing reveals a JAK2 mutation. Diagnosis?

Diagnosis is Polycythemia vera.

1. Definition

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, leading to increased red cell mass, often with leukocytosis and thrombocytosis, and is strongly associated with a JAK2 mutation.

2. Etiology

1. Somatic mutation in JAK2 (V617F or exon 12)
2. Causes constitutive activation of the JAK STAT pathway
3. Leads to growth factor independent hematopoiesis

3. Pathophysiology

1. Clonal expansion of hematopoietic stem cells
2. Results in panmyelosis
3. Increased red cell mass causes hyperviscosity
4. Leukocytosis and thrombocytosis contribute to thrombosis risk
5. Very high platelet counts may cause acquired von Willebrand disease, leading to bleeding
6. Increased cell turnover leads to hyperuricemia
7. Histamine release contributes to aquagenic pruritus

4. Clinical Features

4.1 Hyperviscosity Symptoms

1. Headache
2. Dizziness
3. Blurred vision

4.2 Thrombotic Manifestations

1. Deep vein thrombosis
2. Stroke
3. Myocardial infarction
4. Budd Chiari syndrome
5. Erythromelalgia

4.3 Bleeding Manifestations

1. Epistaxis
2. Easy bruising
3. Gastrointestinal bleeding

4.4 Other Features

1. Aquagenic pruritus
2. Splenomegaly
3. Plethora
4. Early satiety
5. Gout due to hyperuricemia

5. Diagnosis

5.1 Laboratory Findings

1. Elevated hemoglobin and hematocrit
2. Increased red cell mass
3. Leukocytosis
4. Thrombocytosis
5. Low serum erythropoietin

5.2 Bone Marrow

1. Hypercellular marrow
2. Panmyelosis
3. Pleomorphic megakaryocytes

5.3 Molecular Testing

1. JAK2 mutation present in more than 95 percent of cases

6. WHO Diagnostic Criteria

Major Criteria

1. Elevated hemoglobin or hematocrit
2. Bone marrow biopsy showing panmyelosis
3. Presence of JAK2 mutation

Minor Criterion

1. Low serum erythropoietin

Diagnosis requires:

1. All three major criteria, or
2. Two major criteria and one minor criterion

7. Management

7.1 Low Risk Patients

1. Phlebotomy targeting hematocrit less than 45 percent
2. Low dose aspirin

7.2 High Risk Patients

1. Age greater than or equal to 60 years or history of thrombosis
2. Phlebotomy and aspirin
3. Hydroxyurea

7.3 Additional Therapy

1. Ruxolitinib in refractory cases
2. Antihistamines or SSRIs for pruritus
3. Allopurinol for hyperuricemia

8. Complications

1. Thrombosis is the leading cause of morbidity and mortality
2. Hemorrhage
3. Progression to myelofibrosis
4. Transformation to acute leukemia

9. Key Clinical Insight

Aquagenic pruritus + erythromelalgia + splenomegaly + elevated hemoglobin with low erythropoietin + JAK2 mutation = Polycythemia vera

10. Exam Level Pearls

1. JAK2 mutation is present in more than 95 percent of cases
2. Low erythropoietin distinguishes PV from secondary polycythemia
3. Phlebotomy to hematocrit less than 45 percent reduces thrombosis risk
4. Erythromelalgia responds to aspirin
5. Aquagenic pruritus is a classic clue