Cases from Hennepin County Medical Center

Cases involving ventricular septal defect, thyrotoxic periodic paralysis, hepatopulmonary syndrome, and others are discussed.


Case 1: Ventricular septal defect as a complication of myocardial infarction

By Zach Rosol, MD, ACP Resident/Fellow Member

The patient

A 75-year-old woman without prior cardiac disease called 911 for worsening epigastric and retrosternal burning of 2 days' duration, minimally relieved with famotidine and baking soda. She also complained of nausea, vomiting, and chills. A prehospital electrocardiogram (EKG) demonstrated ST elevations in the inferior leads (II, III, aVF) with reciprocal changes in the anterior leads (V1-V3), consistent with acute inferior left ventricular and associated right ventricular infarction. On presentation, blood pressure was 77/48 mm Hg and heart rate was 59 beats/min, with elevated jugular venous pressure (JVP), a third heart sound (S3), and cool extremities that were concerning for cardiogenic shock. Bedside transthoracic echocardiogram demonstrated apical akinesis and a dilated right ventricle.

Transthoracic echocardiogram image apical 4-chamber view with Doppler showing ischemic ventricular septal defect arrow RVequalsright ventricle LVequalsleft ventricle
Transthoracic echocardiogram image (apical 4-chamber view) with Doppler showing ischemic ventricular septal defect (arrow). RV=right ventricle; LV=left ventricle.

The patient was volume resuscitated, received a dobutamine infusion, and underwent emergent cardiac catheterization where a 100% distal right coronary artery (RCA) occlusion was discovered and treated. A few hours after admission to the cardiac ICU, she required increasing amounts of dobutamine and initiation of norepinephrine for worsening hypotension. On repeat physical examination, a new harsh apical systolic murmur was heard. Bedside ultrasound with Doppler demonstrated blood flow from left to right across the ventricular septum, confirmed by formal echocardiogram (Figure 1).

Subsequent right-heart catheterization showed a significant increase in oxygen saturation from right atrium to right ventricle, diagnostic for ventricular septal defect (VSD). An intra-aortic balloon pump was placed prior to emergent surgical repair. Following surgery, she required prolonged support with extracorporeal membrane oxygenation (ECMO) but ultimately survived and was transferred to a long-term acute care hospital for further rehabilitation.

The diagnosis

Ventricular septal rupture and resultant VSD—along with ventricular free-wall rupture and mitral regurgitation from papillary muscle rupture—is 1 of the 3 acute mechanical complications that may follow a completed myocardial infarction (MI). While well-characterized, acute post-MI VSD is rarely seen in the reperfusion era, during which incidence has decreased from 2% to approximately 0.2%. The onset is classically 3 to 5 days post-MI, although it can occur within 24 hours. VSD is most frequently the result of an infarct in the RCA territory but can also occur with left anterior descending coronary artery infarcts. It is more common in women, nondiabetic patients, and patients without a previous MI. A rapid decrease in blood pressure with evidence of biventricular failure (with right generally greater than left) is commonly seen. This is often accompanied by a new murmur, usually holosystolic and heard best at the sternal borders or apex.

Diagnosis can be confirmed by transthoracic echocardiogram or right-heart catheterization showing an increase in oxygenation between the right atrium and right ventricle due to left-to-right shunting. Management centers on stabilizing the airway and hemodynamics prior to surgical intervention. Vasodilators for afterload reduction, inotropic agents to increase cardiac output, and placement of an intra-aortic balloon pump for further afterload reduction may also be necessary. Timing of surgical repair is case-dependent, but early cardiothoracic surgical consultation is essential.

Pearls

  • Ventricular septal defect (VSD) is a well-characterized but uncommon mechanical complication of myocardial infarction, often heralded by the presence of cardiogenic shock and a new holosystolic murmur.
  • Management of ischemic VSD includes hemodynamic support via afterload reduction, inotropic agents, and intra-aortic balloon pump until definitive surgical management can be safely pursued.

Case 2: Thyrotoxic periodic paralysis

By Aman Fasahat, MD, and Nick Briese, MD, ACP Member

The patient

A 32-year-old Asian man with known hyperthyroidism due to Graves' disease presented with 1 day of weakness in both legs. The weakness was most prominent in his thighs and progressed to a point at which he could no longer stand from a seated position. He also reported palpitations, anxiety, tremors, and sweating. He recalled prior episodes of weakness, which resolved spontaneously. He also noted difficulty in adhering to his prescribed antithyroid regimen of methimazole and propranolol.

Physical examination on presentation was notable for a blood pressure of 199/77 mm Hg, heart rate of 124 beats/min, and a temperature of 36.9 °C. He was diaphoretic with no exophthalmos and a normal sized, nontender thyroid. Laboratory testing showed a potassium level of 2.2 mEq/L, a free T4 (thyroxine) level of 4.5 ng/dL (normal range, 0.8 to 1.6 ng/dL), and a completely suppressed thyroid-stimulating hormone level. The thyroid-stimulating immunoglobulin assay was elevated. Following careful replacement of potassium his symptoms resolved, and methimazole was restarted. Definitive treatment with radioactive iodine was administered one week after hospital discharge.

The diagnosis

This patient's diagnosis is thyrotoxic periodic paralysis. Thyrotoxic periodic paralysis is a rare condition, seen most commonly in Asian men in their third or fourth decade. It presents during an overtly hyperthyroid state and is manifested by “attacks” of muscle weakness with a predilection for the lower extremities. Severe cases may also affect the respiratory musculature. Laboratory findings often include significant hypokalemia in addition to thyrotoxicosis. The suspected mechanism is that elevated thyroxine levels induce intracellular shifting of potassium by sensitization of the Na/K–ATPase in patients with a genetic susceptibility.

Treatment of an acute paralytic episode begins with conservative potassium replacement. Although patients may present with markedly low serum potassium, total body potassium is normal, so aggressive potassium replacement may place patients at risk of hyperkalemia. Nonselective beta-blockade (e.g., propranolol) prevents further intracellular potassium shifting. Correction of the underlying hyperthyroidism is the definitive treatment. Episodes of periodic paralysis do not recur once a euthyroid state is achieved and maintained. If hyperthyroidism remains poorly managed, paralysis is typically recurrent.

Pearls

  • Thyrotoxic periodic paralysis is a rare condition that complicates thyrotoxicosis in genetically susceptible individuals and most often presents with episodic acute weakness and hypokalemia.
  • Management includes conservative potassium replacement, nonselective beta-blockade, and treatment of hyperthyroidism.

Case 3: Hepatopulmonary syndrome

By Kathleen Mahan, MD, ACP Resident/Fellow Member

The patient

A 29-year-old woman with a history of adrenal insufficiency on long-term steroid therapy, nonalcoholic steatohepatitis (NASH) status post-liver transplant, and recurrent cirrhosis presented with progressive shortness of breath and pleuritic chest pain. She was found to be hypoxemic, with an oxygen saturation of 80% on room air that corrected with supplemental oxygen. Physical examination was remarkable only for scleral icterus; lungs were clear to auscultation, there was no heart murmur, and she had a soft, nontender abdomen. A chest X-ray, EKG, and D-dimer tests were unrevealing. A chest CT showed atelectasis, portal hypertension with liver cirrhosis, splenomegaly, and esophageal varices.

Laboratory testing was significant for pancytopenia, an international normalized ratio (INR) of 2.1, and elevated aspartate aminotransferase (AST), bilirubin, and alkaline phosphatase levels. She was hypotensive with systolic blood pressure in the 80 mm Hg range and received fluids, stress-dose steroids, and broad-spectrum antibiotics with the working diagnosis of septic shock. Infectious workup was subsequently negative, and antibiotics were discontinued. Although she continued to be hypoxic, it was noted that her oxygen saturation improved at night. Due to the ongoing hypoxemia, she underwent transthoracic echocardiography with “bubble study,” which showed extracardiac right-to-left shunting. Her supplemental oxygen requirements gradually improved to 2 to 3 L via nasal cannula, and she was discharged home with follow-up in the liver transplant clinic.

The diagnosis

This patient's diagnosis is hepatopulmonary syndrome (HPS), which primarily is a complication of chronic liver disease but can also be seen in acute liver failure. The diagnosis of HPS requires 3 criteria: impaired oxygenation, portal hypertension, and intrapulmonary vascular dilations. In addition to signs and symptoms of chronic liver disease, patients may also present with dyspnea and “platypnea-orthodeoxia” (e.g., dyspnea and hypoxemia noted in the upright position). The disease is thought to result from impaired synthesis and metabolism of pulmonary vasoactive substances such as nitric oxide, which causes intrapulmonary vasodilation with predilection for the dependent portions of the lung. Positional hypoxemia results from increased ventilation-perfusion mismatch and diffusion limitations of the dilated alveolar capillaries; supplemental oxygen can sometimes overcome these abnormalities if the intrapulmonary shunting is not too severe. Contrast-enhanced echocardiography (e.g., “bubble study”) is a noninvasive modality for identifying intrapulmonary shunt, but technetium-labeled macroaggregated albumin scan can also be used. Supportive therapy with supplemental oxygen is the most frequently utilized intervention. No effective therapies for hepatopulmonary syndrome are currently available other than liver transplantation.

Pearls

  • Hepatopulmonary syndrome (HPS) is a serious complication in patients with chronic liver disease and is marked by hypoxemia and “orthodeoxia-platypnea.”
  • Treatment of HPS is limited to supplemental oxygen therapy and liver transplantation.

Case 4: “Crack lung”

By Annie Jacobsen, MD, ACP Resident/Fellow Member

The patient

A 38-year-old woman presented with acute-onset shortness of breath and chest pain, progressive over the past 12 hours. She reported no sick contacts or inhalation exposures or an aspiration event. While en route to the hospital, she developed hemoptysis. Initial vital signs revealed a blood pressure of 99/68 mm Hg, a heart rate of 120 beats/min, a respiratory rate of 48 breaths/min, oxygen saturation of 88% on room air, and a temperature of 38.2 °C. On pulmonary examination, she was noted to have tachypnea and poor air flow without wheezes, crackles, or rales. She was tachycardiac with normal JVP and no lower-extremity edema.

Chest X-ray on admission showing diffuse bilateral infiltrates
Chest X-ray on admission showing diffuse bilateral infiltrates.

A chest X-ray showed diffuse bilateral infiltrates (Figure 2). An EKG showed sinus tachycardia and diffuse ST-segment depression. Initial laboratory testing was significant for a leukocytosis with neutrophilia and mildly elevated D-dimer and troponin levels. The patient was given IV fluids, placed on high-flow oxygen, and given empiric antibiotics for a working diagnosis of community-acquired pneumonia. Subsequent testing revealed a negative HIV test and resolution of the diffuse infiltrates noted on the admission chest X-ray. A CT angiogram of the chest showed diffuse ground-glass opacities, consistent with severe infection or acute respiratory distress syndrome. A urine drug screen detected benzoyl ecgonine, the major metabolite of cocaine. Her supplemental oxygen requirements progressively decreased, and by the third hospital day she had complete resolution of symptoms.

The diagnosis

This patient's diagnosis is acute pulmonary toxicity related to inhalational crack cocaine use, also known as “crack lung.” Crack lung is caused by direct lung toxicity from oxidative stress of drug metabolites and pathologically is associated with diffuse alveolar damage and hyaline membrane formation. While mild and transient respiratory symptoms such as cough are common (20% to 60%) immediately following crack cocaine use, the incidence of crack lung is difficult to estimate due to low health care utilization in this population, lack of patient self-reporting or knowledge of cocaine exposure, and clinician misdiagnosis.

This entity can be difficult to identify, as it can masquerade as pulmonary embolism, asthma exacerbation, Pneumocystis jiroveci pneumonia, or acute respiratory distress syndrome. Symptom onset is within 48 hours of exposure to crack cocaine and may include productive cough, dyspnea, wheezing, hemoptysis, melanoptysis, and pleuritic chest pain. Respiratory support is the mainstay of treatment and may require mechanical ventilation for hypoxia and increased work of breathing that is refractory to noninvasive methods. Steroids are sometimes administered, although consensus on their utility is lacking. Clinical improvement is usually rapid, within 1 to 2 days.

In addition to the acute pulmonary syndrome of crack lung, with repeated exposure, inhalation of cocaine is associated with chronic, irreversible lung disease, including interstitial fibrosis, emphysema, and pulmonary hypertension. The diagnosis of crack lung may provide an opportunity to connect patients with substance and behavioral health resources before the onset of more permanent cocaine-related organ damage.

Pearls

  • “Crack lung” refers to an acute pulmonary toxicity that results from inhalational cocaine exposure.
  • Crack lung is a diagnosis of exclusion, as symptoms are nonspecific and can be seen in many other common acute pulmonary conditions.

Case 5: Acute promyelocytic leukemia manifesting as post-partum hemorrhage

By Faraz Kazmi, MBBS

The patient

A 21-year-old woman was admitted from clinic for evaluation of pancytopenia. Two weeks earlier, she had had a spontaneous vaginal delivery complicated by postpartum hemorrhage attributed to retained placental membranes, uterine atony, and early disseminated intravascular coagulation (DIC). She was stabilized with 2 units of packed red blood cells and 1 unit of cryoprecipitate and then was discharged 2 days after delivery without further evidence of bleeding. At outpatient follow-up, she was found to have a platelet count of 75,000 cells/µL, a white blood cell count of 1,300 cells/µL, an absolute neutrophil count of 0.26, and a hemoglobin level of 9.5 g/dL. Baseline labs from 2 years earlier revealed normal blood counts. At the time of admission, the patient reported mild vaginal bleeding, requiring 2 pads per day since delivery.

Bone marrow aspirate with leukemic promyelocytes containing Auer rods arrow
Bone marrow aspirate with leukemic promyelocytes containing Auer rods (arrow).

On examination, she was afebrile with normal vital signs. Conjunctival pallor was noted. Skin was also pale but without ecchymoses or petechiae. Cardiopulmonary examination was unremarkable. Review of systems was negative aside from fatigue and a transient upper respiratory tract infection. She was not taking any medications. Further workup revealed an INR of 1.3, a D-dimer level of 1,091 ng/mL (normal range, 0 to 229 ng/mL), and a fibrinogen level of 118 mg/dL (normal range, 200 to 400 mg/dL), consistent with low-grade DIC. A peripheral smear was unrevealing. Bone marrow biopsy was obtained and demonstrated promyelocytes with Auer rods (Figure 3). Subsequent fluorescent in situ hybridization (FISH) testing demonstrated a 15;17 chromosomal translocation.

The diagnosis

This patient was diagnosed with acute promyelocytic leukemia (APL). APL is one of the most aggressive forms of acute myeloid leukemia and a true hematologic emergency due to a high rate of early death from DIC-associated hemorrhage. Patients often present with pancytopenia (including leukopenia) and DIC without an obvious provoking cause. This patient's postpartum bleeding complication was likely the result of her undiagnosed malignancy. Preliminary findings on peripheral smear and/or bone marrow biopsy may show characteristic leukemic cell morphology. Treatment with all trans retinoic acid (ATRA) should be started as soon as APL is suspected without waiting for diagnostic confirmation by FISH analysis for the pathognomonic t(15;17). For patients started on therapy before onset of severe bleeding complications, prognosis is very good, with 5-year overall survival rates approaching 90%. APL has much better survival than other forms of acute myeloid leukemia due to the unique ability of ATRA to induce maturation of the malignant promyelocytes. In addition to ATRA, treatment may also include arsenic trioxide (ATO) and chemotherapy, depending on disease risk stratification.

Although effective, treatment with ATRA is not benign, as patients must be closely monitored for several weeks after initiating therapy for development of the differentiation syndrome. Manifested by hypotension, fever, pulmonary infiltrates, and peripheral edema, differentiation syndrome is caused by rapidly maturing promyelocytes releasing cytokines and causing widespread capillary leak. Treatment of this complication is prompt cessation of ATRA and initiation of steroids. This patient experienced no treatment-related complications and after her first cycle of ATRA plus ATO demonstrated complete remission.

Pearls

  • Acute promyelocytic leukemia is a rare disease that should be suspected in young to middle-aged adults presenting with pancytopenia, disseminated intravascular coagulation, and characteristic leukemic cells (promyelocytes with Auer rods) on peripheral smear and/or bone marrow biopsy.
  • As early mortality is high, treatment with all trans retinoic acid is started presumptively before diagnosis is confirmed with additional testing.