Clinical Case Conference

General Cardiology Lecture Series

Anish S. Shah, MD, MS

Division of Cardiology, Department of Medicine, University of Illinois Chicago

2024-04-08

Introduction

Objectives

  1. Understand the cognitive processes involved in the case-based diagnostic reasoning
  2. Identify diagnostic assumptions that may lead towards case-specific biases
  3. Practice contextualizing clinical data in the framework of cardiovascular physiology

History & Physical

30 year old gentleman with a history of acid reflux on PPI therapy, generalized anxiety disorder without long-term therapy, exercise-induced asthma on SABA inhaler therapy.

He had recurrent episodes of wheezing and cough over past 4-6 months, and was sent to the emergency room after being found to have a arterial saturation of 87% on room air.

Reports that he most prominently noted his dyspnea during sexual intercourse with his wife.

He improved with nebulizer therapy. Was seen by ENT at similar time, noting no upper respiratory causes for his symptoms.

Electrocardiography and chest roengenography was performed during his ER visit.

Electrocardiography

Chest Roentgenography

Problems

Sinus tachycardia

Right axis deviation with inferior qR and lateral rS pattern

Complete interpolation of ventricular ectopy with superior axis and inverted transition at V2-V3

Enlarged left-sided heart border with narrow vascular pedicle

Earlier completely interpolated atrial depolarizations, as compared with PVC, at similar cycle length.

Left posterior fascicular block

Inferior/posterior-septal PVC

Cardiomegaly

Poor or abnormal VA conduction?

Patient describes a 10+ year history of anabolic steroid usage, initiated by his coach while he trained as a body-builder.

He continued as he was unsure on how to taper.

He had been on multiple testosterone and anabolic steroid supplements, and had most recently (past 3-6 months) trialed growth hormone.

Growth hormone was stopped due to lower extremity and hand swelling.

Additional histories

Maternal grandfather died of sudden death at age 40, and mother has a potential “mitral valve prolapse”. Father was a body-builder and had taken steroids previously. No foreign travel, raised in Canada and lives in Chicago currently.

No pets. Has a 1-year old son with his wife, who are both healthy.

Medications

  • Chlorodehydromethyltestosterone (CDMT, a.k.a. turinabol)
  • Oxandrolone (active)
  • Testosterone supplementation (active)
  • Growth hormone injections (for 3-6 months prior to presentation)
  • Albuterol inhaler PRN
  • Omeprazole 40 mg PO daily

Examination

Initial vitals of 173/92 and heart rate of 122 bpm that decreased to 137/75 and 109 bpm after rest. SaO2 of 94-96% on room air. BMI 28, 93 kg.

Anxious appearing young gentleman, mildly pressured speech. Skin is warm and dry, Fitzpatrick class I. Mild androgenic alopecia. Not overly-muscular.

JVP at level of clavicle at 30˚. Normal carotid upstroke. PMI is laterally displaced. No obvious thrills or heaves. S1 with physiologically split S2. III/VI systolic murmur apparent at axilla. No peripheral edema, with +2 radial and posterior tibialis pulses.

Labs

Sodium 138
Potassium 4.0
Chloride 102
CO2 24
BUN 29

Creatinine 1.96

AST 35

ALT 52

Hg 17.5
WBC 8 (normal differential)
PLT 208
HbA1c 5.2%

LDL 165, HDL 34
Troponin I 105 (ng/L)
BNP 289

UDS negative

Surface Echocardiography

Problems

Severely reduced LV systolic function with EF < 20%

LV cavity during diastole of ~7.5 cm

LVOT VTI of 9 cm and RVOT VTI of 6 cm

Regional wall motion abnormalities with inferior hypokinesis/akinesis

Moderate to severe mitral regurgitation

Echodensity in apex

Grade III diastolic dysfunction

Left posterior fascicular block
Inferior/posterior septal PVC

Cardiomegaly

Severe systolic dysfunction

Dilated cardiomyopathy

Mitral regurgitation IIIb

Low cardiac output state

Apical thrombus

Differential

Genetic

TTN
LMNA
MYH7
FLNC (filamin C)
RBM20 (RNA-binding motif-20)
TNNT2
TTNC1
PLN (phospholamban)
DSP (desmoplakin)
ACTC1
SCN5A
TPM1 (tropomyosin)

Infectious

COVID/viral myocarditis
Chagas disease
Endomyocardial fibrosis

Immune-mediated

Giant-cell myocarditis
Eosinophilic myocarditis
Sarcoidosis

Ischemic

Plaque rupture syndrome
Coronary artery spasm
Spontaneous coronary artery dissection

Others

Thiamine deficiency (beri-beri)
Selenium deficiency
Hypocalcemia
Hyper/hypo-thyroidism
Tachycardia-induced
Alcohol-induced
Amphetamine-induced
Catecholamine-induced (stress-induced, e.g. Takotsubo)
Anabolic steroid-induced
Hemochromatosis
Wilson’s disease

Sliwa et al. (2023)

Additional Labs

TSH/T4 normal

ACTH 20.4
Free cortisol 1.0
AM cortisol 13
FSH < 0.2
LH < 0.2
Testosterone 1445 ng/dL

Lp(a) 21, ApoB100 126 (mg/dL)
Cystatin 0.9 (eGFR 81)

Ferritin 194
Iron 70
Normal cerruloplasmin
TB negative
HIV negative
RVP negative
Hepatitis panel negative
Trypanasoma cruzi IgG negative
ANA/Anti-SM negative
SPEP/UPEP negative

Differential

Genetic

TTN
LMNA
MYH7
FLNC (filamin C)
RBM20 (RNA-binding motif-20)
TNNT2
TTNC1
PLN (phospholamban)
DSP (desmoplakin)
ACTC1
SCN5A
TPM1 (tropomyosin)

Infectious

COVID/viral myocarditis
Chagas disease
Endomyocardial fibrosis

Immune-mediated

Giant-cell myocarditis
Eosinophilic myocarditis
Sarcoidosis

Ischemic

Plaque rupture syndrome
Coronary artery spasm
Spontaneous coronary artery dissection

Others

Thiamine deficiency (beri-beri)
Selenium deficiency
Hypocalcemia
Hyper/hypo-thyroidism

Tachycardia-induced

Alcohol-induced
Amphetamine-induced
Catecholamine-induced (stress-induced, e.g. Takotsubo)

Anabolic steroid-induced

Hemochromatosis
Wilson’s disease

  1. Steroid-induced cardiomyopathy
  2. Genetic/dilated cardiomyopathy
  3. Tachycardia-mediated cardiomyopathy
  4. Ischemic cardiomyopathy

Steroid-induced cardiomyopathy

Anabolic-androgenic steroid (AAS) misuse, above that of replacement hormone levels, is common - up to 2% of men in the US (Pope et al., 2014)

AAS abuse tends to involve dosing 5-30 times greater than recommended by the Endocrine Society (Garner et al., 2018).

In a small study (n = 140), AAS users had an LVEF 10% lower than age-matched non-users (Baggish et al., 2017).

Baggish et al. (2017)

AAS agents?

  • Testosterone is predominately bound to sex hormone-binding globulin, with only 1-2% being free
  • Once bound to androgen receptors, initiates gene transcription
  • AAS agents mimic testosterone, but maximize anabolic effect and minimize androgenic effects
  • Available orally or as injectable agents
  • Used in “cycles” however can become dependent, develop tolerance and have withdrawal with cessation (Garner et al., 2018)
  • Additional effect leads to dyslipidemia with high LDL and lower HDL, including increased coronary plaque volume (Fadah et al., 2023)

Fadah et al. (2023)

But the growth hormone?

  • Growth hormone deficiency is common in heart failure
  • Salzano et al. (2018) reviewed studies on the effect on treatment with growth hormone on cardiac function, however mixed results:
    • Improved functional class and exercise duration/capacity
    • Improved VO2
    • Decreased LV size, reverse remodeling, and improved LVEF
    • Decrease HF-associated inflammatory cytokines
  • Did on-and-off growth hormone mask some of the effects of AAS?

Salzano et al. (2018)

Cardiac catheterization

Right/left heart catherization with selective coronary angiography

Problems

Hypovolemic “shock” requiring nor epinephrine with light sedation

Large diameter coronary vessels (4-5 mm) without obstructive disease

Diffuse ectasia of RCA with diminutive branch vessels

Left posterior fascicular block
Inferior/posterior septal PVC
Severe systolic dysfunction
Dilated cardiomyopathy
Mitral regurgitation IIIb

Low cardiac output state

Apical thrombus

Spontaneous coronary artery dissection?

Arterial pressure and resistance training

MacDougall et al. (1985) tested the acute hypertensing response to resistance training, with invasive brachial artery pressure transduction.

  • Single-arm curls of 255/190
  • Double-leg press of 320/250 (peak 480/350)

MacDougall et al. (1985)

Rare cases of SCAD seen with resistance training (Aghasadeghi & Aslani, 2008)

Fahmy et al. (2016) described a population of men and women with SCAD. Men (v. women) had a higher rate of…

  • Being younger
  • Isometric exercise
  • Heavy-weight resistance training
  • Recreational drugs

Aghasadeghi & Aslani (2008)

Cardiac Magnetic Resonance Imaging

Cine imaging

Generally, steady-state free precession (SSFP) is used in the generation of cine imaging.

RF pulses produce free induction decay curves or signals, and corresponding echos. When in rapid sequence, the signal will began to merge and never reach zero, achieving a continuous signal of varying amplitude \(\rightarrow\) SSFP.

For CMR, these sequences are repeated throughout a cardiac cycle.

Gadolinium contrast!

Gadolinium (Gd) is a paramagnetic substance (becomes temporarily magnetized), out of four elements (Fe, Ni, Co). Gd induces T1 relaxation.

T1 is the time it takes for net magnetization to return to initial maximum value (shortened by Gd).

Initially, T1 scouting identifies the inversion time at which viable myocardium is “dark”.

https://mriquestions.com/ps-phase-sensitive-ir.html

Phase-corrected inversion recovery sequences are less reliant on a set inversion time

Next sequence is done with free-breathing.

Problems

Dilated LV with severely reduced LV function

Inferior wall akinesis

Inferior wall showed transmural, from base to apex late gadolinium enhancement

Thrombus seen in the apex

Left posterior fascicular block
Inferior/posterior septal PVC

Severe systolic dysfunction
Dilated cardiomyopathy

Mitral regurgitation IIIb
Low cardiac output state

Apical thrombus

Spontaneous coronary artery dissection?

Differential

Genetic

TTN
LMNA
MYH7
FLNC (filamin C)
RBM20 (RNA-binding motif-20)
TNNT2
TTNC1
PLN (phospholamban)
DSP (desmoplakin)
ACTC1
SCN5A
TPM1 (tropomyosin)

Infectious

COVID/viral myocarditis
Chagas disease
Endomyocardial fibrosis

Immune-mediated

Giant-cell myocarditis
Eosinophilic myocarditis
Sarcoidosis

Ischemic

Plaque rupture syndrome
Coronary artery spasm

Spontaneous coronary artery dissection

Others

Thiamine deficiency (beri-beri)
Selenium deficiency
Hypocalcemia
Hyper/hypo-thyroidism

Tachycardia-induced

Alcohol-induced
Amphetamine-induced
Catecholamine-induced (stress-induced, e.g. Takotsubo)

Anabolic steroid-induced

Hemochromatosis
Wilson’s disease

Clinical Course

Hospitalization:

  1. Patient was admitted to the cardiology service
  2. Nephrology and endocrine consultation
  3. Underwent coronary angiography and right heart catheterization
  4. Underwent cardiac magnetic resonance imaging
  5. Discharged with LifeVest

Treatment:

  • cessation of AAS
  • atorvastatin 20
  • apixaban 5 bid
  • sacubitril-valsartan 24/26
  • empagliflozin 10

Thoughts?

References

Aghasadeghi, K., & Aslani, A. (2008). Spontaneous coronary artery dissection in a professional body builder. International Journal of Cardiology, 130(3), e119–e120. https://doi.org/10.1016/j.ijcard.2007.06.151
Baggish, A. L., Weiner, R. B., Kanayama, G., Hudson, J. I., Lu, M. T., Hoffmann, U., & Pope, H. G. (2017). Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use. Circulation, 135(21), 1991–2002. https://doi.org/10.1161/CIRCULATIONAHA.116.026945
Fadah, K., Gopi, G., Lingireddy, A., Blumer, V., Dewald, T., & Mentz, R. J. (2023). Anabolic androgenic steroids and cardiomyopathy: An update. Frontiers in Cardiovascular Medicine, 10. https://doi.org/10.3389/fcvm.2023.1214374
Fahmy, P., Prakash, R., Starovoytov, A., Boone, R., & Saw, J. (2016). Pre-Disposing and Precipitating Factors in Men With Spontaneous Coronary Artery Dissection. JACC: Cardiovascular Interventions, 9(8), 866–868. https://doi.org/10.1016/j.jcin.2016.02.024
Garner, O., Iardino, A., Ramirez, A., & Yakoby, M. (2018). Cardiomyopathy induced by anabolic-androgenic steroid abuse. BMJ Case Reports, bcr-2017-223891. https://doi.org/10.1136/bcr-2017-223891
MacDougall, J. D., Tuxen, D., Sale, D. G., Moroz, J. R., & Sutton, J. R. (1985). Arterial blood pressure response to heavy resistance exercise. Journal of Applied Physiology (Bethesda, Md.: 1985), 58(3), 785–790. https://doi.org/10.1152/jappl.1985.58.3.785
Pope, H. G., Kanayama, G., Athey, A., Ryan, E., Hudson, J. I., & Baggish, A. (2014). The lifetime prevalence of anabolic-androgenic steroid use and dependence in Americans: Current best estimates. The American Journal on Addictions, 23(4), 371–377. https://doi.org/10.1111/j.1521-0391.2013.12118.x
Salzano, A., Marra, A. M., D’Assante, R., Arcopinto, M., Suzuki, T., Bossone, E., & Cittadini, A. (2018). Growth Hormone Therapy in Heart Failure. Heart Failure Clinics, 14(4), 501–515. https://doi.org/10.1016/j.hfc.2018.05.002
Sliwa, K., Viljoen, C. A., Hasan, B., & Ntusi, N. A. B. (2023). Nutritional Heart Disease and Cardiomyopathies. Journal of the American College of Cardiology, 81(2), 187–202. https://doi.org/10.1016/j.jacc.2022.08.812