Cardionerds: A Cardiology Podcast

CardioNerds (Amit Goyal & Daniel Ambinder) join Cleveland Clinic cardiology fellows (Ben Alencherry, Erika Hutt, Zach Il’Giovine, Kara Denby) for some delicious craft beer at Platform Brewery! They discuss a challenging case of Ehlers Danlos Syndrome with Papillary Muscle Rupture. Dr. Vidyasagar Kalahasti provides the E-CPR and program director Dr. Venu Menon provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident, Eunice Dugan, with mentorship from University of Maryland cardiology fellow Karan Desai.   This case has been published in JACC Case Reports: CardioNerds Corner! Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A pregnant woman at 29 weeks gestation presents with postpartum pulmonary edema, found to have papillary muscle rupture, is ultimately diagnosed with vascular Ehlers Danlos Syndrome. For a detailed course, enjoy the JACC case report. Case Media Visit the JACC Case Reports: CardioNerds Corner to review the case media! Episode Schematics & Teaching Coming soon! The CardioNerds 5! – 5 major takeaways from the #CNCR case What is Ehlers-Danlos Syndrome?   Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogenous group of heritable connective tissue disorders due to altered collagen metabolism. The inheritance pattern is variable, but is mostly autosomal dominant, with a range of mechanisms including deficiency of collagen-processing enzymes, mutant collagen chains, and haploinsufficiency.     Although the syndrome has varying and overlapping clinical manifestations based on subtype (per the 2017 International ED Consortium there are 17 subtypes) it is largely characterized by hyperextensibility of the skin, hypermobility of joints, atrophic scarring, and tissue fragility.  The cardiovascular system is involved in the vascular and cardio-valvular subtypes.  The incidence is estimated to be 1 in 2500 to 5000, however this is likely an underestimation since mild presentations may not be clinically diagnosed nor sent for genetic testing.    The differential diagnosis for suspected EDS includes osteogenesis imperfecta, Marfan syndrome, and Loeys-Dietz syndrome. Those with joint symptoms may be incorrectly diagnosed with fibromyalgia, chronic fatigue syndrome etc.    What is vascular EDS?   There are many subtypes of EDS. Type IV or vascular EDS (vEDS) is an autosomal dominant disorder that affects Type III procollagen protein synthesis. The incidence is rare – 1 in 50,000 to 250,000 people and is ~5% of all EDS cases.    It is commonly caused by a defect in the COL3A1 gene, most of which are single base substitutions, but more than 700 different mutations have been identified. Missense mutations at the C-terminal end of the molecule results in a more severe form of the disease.  Feared vascular manifestations include arterial dissection, rupture, and aneurysm formation. Death is most frequently secondary to complications from arterial dissection or hollow organ rupture. 70% of patients experience a first major event by age 20. Note, surgical repair of a ruptured aneurysm or dissection can be complicated by poor wound healing or hemorrhage because tissue in Ehlers-Danlos is friable.  In this subtype, the usual manifestations of joint hypermobility and skin hyperextensibility may not be as apparent.  The vascular type has the worst prognosis with median expectancy between 40-50 years of age.   How is vEDS diagnosed?   Vascular EDS should be considered in anyone with unexplained arterial or hollow viscus rupture, commonly the sigmoid colon, especially at a young age.  Diagnosis is confirmed by either finding of structurally abnormal type III procollagen in a culture of dermal fibroblasts or COL3A1 gene mutation. Clinical criteria can aid in the decision to pursue testing.    Molecular testing is recommended when meeting one or more major clinical criteria or several minor criteria. Major criteria include family history of vEDS, unexplained arterial rupture at young age, spontaneous intestinal  perforation (in absence of risk factors), uterine rupture during pregnancy and labor, or carotid-cavernous sinus fistula formation.    Some minor criteria include bruising without trauma (especially in unusual locations), spontaneous pneumothorax, tendon/muscle rupture, gingival recession, early onset varicose veins, and characteristic facial appearance amongst other criteria. Characteristic facial features include presence of prominent eyes due to lack of adipose tissue around the orbit, thin punched nose, small lips, hollow cheeks, and lobeless ears.   How should patients with vEDS be managed?   Management of patients with vEDS requires a multidisciplinary team including a clinical geneticist. Baseline arterial imaging is needed but recommendations for follow-up imaging are not well defined. TTE should be performed at least every 3 years, to screen for cardiac complications.    Contact sports should be avoided, as should anti-platelet and anti-coagulation therapy to minimize bleeding risks. Arterial and intramuscular punctures, arteriography, and routine colonoscopy should also be avoided. Surgical or endovascular management of complications can be challenging due to tissue friability.   Ascorbic acid is a co-factor for collagen fibrils and may reduce bruising. Desmopressin, vasopressin, and recombinant factor 8a have also been shown to reduce bleeding complications.   Patients with vEDS have decreased intima media thickness which imposes additional mechanical stress onto already fragile tissue. Celiprolol is a cardio-selective beta blocker and beta-2 partial agonist which has been showing to prevent arterial complications. However, this drug lacks FDA approval and is not available in the USA.   Importantly, cascade genetic testing should be offered to all first-degree relatives.   How can pregnancy–related complications be avoided?   Pregnancy in women with vEDS is considered high risk with maternal death rates over 10%. Pregnancy increases risks in two major ways: (1) increased risk of complications related to the gravid uterus and hypermobility (e.g., premature rupture of membranes, ligament laxity and rupture) or uterine/vascular rupture; (2) worsening of pre-existing pathology such as mitral valve prolapse of aortic dilation due to physiologic changes during pregnancy.    Pre-pregnancy risk stratification and counseling is recommended for those with known vEDS. Some recommend termination of pregnancy in patients with known vEDS, but one study suggests that pregnancy does not influence life-expectancy. Current guidelines recommend a risk-benefit discussion with the patient and their family.    In a patient with vEDS who becomes pregnant, care should involve a multidisciplinary team at a specialized center with vascular surgery, general surgery, and high-risk obstetrics. It is uncertain which mode of delivery improves the risk-benefit ratio for the patient and fetus. Furthermore, spinal or epidural anesthesia can have increased risk of complications in patients with vEDS.  The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. References Hutt, Erika, Celeste Santos-Martins, Jose Aguilera, Per Wierup, Vidyasagar Kalahasti, and Carmela Tan. “A 27-Year-Old Woman With Postpartum Papillary Muscle Rupture.” JACC: Case Reports, October 2020, S2666084920311748.   M.J. Eagleton. Arterial complications of vascular Ehlers-Danlos syndrome. J Vasc Surg, 64 (2016), pp. 1869-1880  Miklovic, Tyler, and Vanessa C. Sieg. “Ehlers Danlos Syndrome.” In StatPearls. Treasure Island (FL): StatPearls Publishing, 2020.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

Dr. Binh An Phan provides E-CPR and Dr. Atif Qasim shares a message for applicants. They discuss a case of STEMI due to coronary vasospasm, delving into the diagnostic process and treatment options. The episode highlights the physiology of vasospasm, risk factors, and management complexities. UCSF fellows share insights on clinical training experiences and complex cardiac cases, emphasizing the importance of comprehensive care in challenging scenarios.

In this episode, cardiology fellows Jack Hornick, Phoo Pwint Nandar, and Sideris Facaros from Summa Health dive into a complex case of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). They explore a patient's unexpected palpitations and dizziness, unraveling diagnostics like EKG analysis and the nuances of ventricular tachycardia. Dr. Kenneth Varian adds expert insight on management strategies, including the necessity of multi-disciplinary approaches and the role of genetic testing in ARVC. Join them as they merge intriguing medical discussions with the beauty of nature!

CardioNerds (Amit Goyal & Daniel Ambinder) join Scripps cardiology fellows (Christine Shen and Andrew Cheng) for some Cardiology and California Burritos in San Diego! They discuss an informative case of Wet Beriberi and Stiff Left Atrial Syndrome. Dr. Thomas Heywood provides the E-CPR and program director Dr. Malhar Patel provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Tommy Das with mentorship from University of Maryland cardiology fellow Karan Desai. Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A woman in her mid-60s with history of rheumatic mitral stenosis s/p mechanical mitral valve replacement, HFpEF, and paroxysmal atrial fibrillation s/p ablation presents with subacute worsening dyspnea despite escalating diuretic doses. TTE shows an EF of 62%, normal gradients across the mitral valve without mitral regurgitation, and a dilated IVC. She is admitted with a presumed diagnosis of decompensated heart failure, and started given IV furosemide. Her symptoms slightly improve though do not resolve, and her creatinine increases from 1.4 to 2.1.   In light of the unclear hemodynamic picture, a RHC is done, showing a RA pressure 9, RV pressure of 80/10, PAP 70/25 with mPAP 40, PCWP 30, SVR 872, CO 11 (by thermodilution), and CI 5.2. Notably, large V waves are noted on the RHC. Given concern for mitral regurgitation in the setting of large V waves, a TEE was pursued, which confirmed the lack of MR seen on TTE. Thus, her large V waves were felt to be due to stiff left atrial syndrome, and a cardiac CT showed a severely calcified “coconut left atrium”. Labwork revealed a profoundly low thiamine level (21, with LLN of 70), raising concern for wet beri beri syndrome.   The patient’s unifying diagnosis was indolent left atrial syndrome that was exacerbated by high outout heart failure due to Wet Beri Beri syndrome. The patient received thiamine supplementation, and was diuresed to euvolemia with dramatic improvement in symptoms. A repeat RHC after thiamine replacement showed a CO of 5.7 and CI of 2.74 by thermodilution, demonstrating resolution of her high output heart failure.   Case Media A B C D E F Click to Enlarge A. CXRB. ECGC. RHC: large V waves are noted on the RHCD. CO 11 and CI 5.2 by thermodilution pre-treatment E. Cardiac CT showed a severely calcified “coconut left atrium”F. Repeat CO of 5.7 and CI of 2.74 by thermodilution after thiamine replacement TTE 1 TTE 2 TEE 1 – Mitral Valve TEE 2 – Mitral Valve Cardiac CT Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1) This case featured a patient with Stiff Left Atrial Syndrome! Cardionerds, what the heck is that?   Stiff Left Atrial Syndrome (SLAS) is fundamentally a disorder of atrial compliance, wherein a non-compliant left atrium (LA) leads to abnormal atrial diastole. During LV systole (atrial diastole), the LA receives blood from the low-resistance pulmonary veins. Under normal conditions, the LA pressures initially fall (x-descent). Then, as the atrium fills from both RV contraction and passive filling from the pulmonary veins, there is a steady and modest rise in LA pressure (v-wave). In patients with decreased LA compliance, the V-wave may be accentuated.   In SLAS, left atrial compliance is significantly decreased, leading to very large v-waves that reflect the inability to accommodate LA filling and the steepened slope of the pressure-volume curve (see the below diagram from Urey et al). This leads to dramatically increased LA pressures during LV systole (especially in late LV systole), contributing to post-capillary pulmonary hypertension over time and symptoms of dyspnea on exertion.   2) Which patients are at risk of developing SLAS, how is it diagnosed, and how is it managed?   Stiff Left Atrial Syndrome was first described in the late 1980s as a complication of mitral valve surgery, and has been increasingly recognized as a complication of left atrial ablation procedures leading to atrial fibrosis. While the condition is relatively rare (occurring in ~1.4% of patients following ablation), significant heart failure symptoms and pulmonary hypertension can develop.   While no diagnostic criteria exist, SLAS should be considered in patients with HFpEF, a small or calcified LA on imaging, and risk factors including mitral valve surgery and/or prior left atrial ablations. Invasive hemodynamics will show large v-waves in the absence of mitral regurgitation (or disproportionate to the degree of MR) and an elevated PCWP out of proportion to the LVEDP. It is important to exclude pulmonary vein stenosis, another potential complication of ablation.   Management consists primarily of diuretics and reducing ventricular afterload as tolerated, though an intra-atrial septostomy could be considered in refractory cases.   Notably, SLAS may be asymptomatic in many patients due to the compliance of the pulmonary venous vascular system, which can store blood volume without significant increases in pressure. However, this compliance could become overwhelmed in certain stressed states or exercise.  3) Our patient experienced a stressor in the form of high output heart failure; what is the pathophysiology of high output heart failure, and what is your differential for high output heart failure?  While a number of causes for high output heart failure exist, they share an underlying pathophysiology of excessively decreased systemic vascular resistance and increased metabolic demand. The persistently low SVR leads to decreased ventricular afterload, increased LV emptying and thus increased stroke volume and cardiac output. This subsequently leads to increased preload and symptoms of congestive heart failure. Furthermore, increased oxygen demands requires increased cardiac output. Additionally, the persistently low SVR causes low renal perfusion pressure (renal hypoperfusion) which leads to RAAS activation and volume expansion  Diagnosis is based on echocardiographic evaluation, RHC hemodynamics, and an identified cause of a high output state. TTE may show normal or reduced ejection fraction; additional findings may include a dilated IVC, RV enlargement or dysfunction, elevated estimated pulmonary artery pressures, and/or LV enlargement. RHC typically shows a CO > 8 L/min or a CI > 4 L/min/m2, though these cutoffs are not absolute.   The differential for high output heart failure includes etiologies secondary to predominantly low SVR (e.g., obesity, cirrhosis, AV fistula) versus those secondary to increased metabolic drive (e.g., hyperthyroidism, myeloproliferative disorders). See the CNCR episode from the Johns Hopkins Hospital for more details!   4) How does thiamine deficiency lead to high output heart failure?   Thiamine is vital to aerobic metabolism in the Krebs cycle and the Pentose Phosphate Pathway. In states of thiamine deficiency, anaerobic metabolism is favored over aerobic metabolism, leading to increased levels of lactate and pyruvate. This leads to a decrease in adenosine triphosphate (ATP) and increase in adenosine monophosphate (AMP), which is released into skeletal muscle as adenosine. This release of adenosine leads to vasodilation and decreased systemic vascular resistance through shunt physiology.  Arterial hypoperfusion of the kidneys leads to activation of the RAAS and expansion of plasma volume. Increased oxygen demand lead to an increased cardiac output.  Importantly, CO by thermodilution and Fick may be discrepant in Beriberi! This is because mitochondria are unable to utilize O2 by performing aerobic metabolism. Thus, less oxygen is extracted from the blood, and venous oxygen saturations will be relatively elevated. This may leads to an erroneously elevated CO by Fick’s method as compared to thermodilution!  5) Lets bring it all together! Cardionerds, what is your illness script for Beriberi?   Pathophysiology: As detailed above, thiamine deficiency causes an increase in anaerobic metabolism, increased oxygen demand and systemic vasodilation through increased adenosine levels.   Epidemiology: Patient populations at risk for severe thiamine deficiency include patients with severe malnutrition, chronic alcohol use, incarceration, social isolation, refugee populations, history of bariatric surgery, or chronic loop diuretic use. Notably, 90% of patients on diuretics can develop some level of thiamine deficiency.  Signs/Symptoms: “Dry” beriberi involves symmetrical peripheral neuropathy, primarily in the distal extremities. “Wet” beriberi is characterized by high output heart failure and can lead to shock in severe cases.   Diagnosis: Thiamine deficiency is difficult to diagnose. Blood thiamine levels can be low in acute illness and do not reflect total body stores. Erythrocyte transketolase activity and thiamine pyrophosphate effect tests can be used, though these tests have poor specificity and sensitivity. The gold standard is high performance liquid chromatography, though access to this test is expensive and not commonly available.   As a historical note, in 1945, Marion Blankenford developed diagnostic criteria for wet beriberi, which includes evidence of an enlarged heart with normal rhythm, dependent edema, elevated venous pressure, peripheral neuritis or pellagra, nonspecific alternans on ECG, no evidence of other cardiac disease, at least 3 months of thiamine deficiency, and improvement in symptoms and reduction in heart size following thiamine replacement.   Treatment: The cornerstone of wet beriberi management is supportive treatment of heart failure while replacing thiamine stores. A rapid and dramatic improvement following thiamine replacement is diagnostic of wet beriberi.   References Bisbal, F., Baranchuk, A., Braunwald, E., et al. (2020). Atrial Failure as a Clinical Entity: JACC Review Topic of the Week. Journal of the American College of Cardiology, 75(2), 222–232.   Gibson, D. N., Di Biase, L., Mohanty, P., Patel, J. D., Bai, R., Sanchez, J., Burkhardt, J. D., Heywood, J. T., Johnson, A. D., Rubenson, D. S., Horton, R., et al. (2011). Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors. Heart rhythm, 8(9), 1364–1371.   Maeder, M. T., Nägele, R., Rohner, P., & Weilenmann, D. (2018). Pulmonary hypertension in stiff left atrial syndrome: pathogenesis and treatment in one. ESC heart failure, 5(1), 189–192.   Urey, M. A., Darden, D., Stoller, D., et al. (2017). Stiff Left Atrial Syndrome After Multiple Percutaneous Catheter Ablations: Role for Invasive Hemodynamic Exercise Testing. Circulation. Heart failure, 10(5), e003885.   Durstenfeld, M. S., & Hsue, P. Y. (2020). An Unusual, Reversible Cause of Acute High-Output Heart Failure Complicated by Refractory Shock. Circulation, 142(9), 901–905.   Reddy, Y., Melenovsky, V., Redfield, M. M., Nishimura, R. A., et al. (2016). High-Output Heart Failure: A 15-Year Experience. Journal of the American College of Cardiology, 68(5), 473–482.   CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Karan Desai) join University Hospitals Cleveland Medical Center cardiology fellows (Tarek Chami, Jamal Hajjari, and Haytham Mously) for some amazing pizza and coffee in Cleveland, Ohio! They discuss an important case of effusive constrictive pericarditis. Dr. Brian Hoit provides the E-CPR and assistant program director Dr. Claire Sullivan provides a message for applicants. We are grateful to chief fellow Scott Janus for his leadership in planning this episode! Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai. Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A woman in her mid-70s presented to clinic with subacute onset shortness of breath. Her past medical history includes metastatic breast cancer s/p mastectomy, chemo/radiation, and hormonal therapy. Exam notable for tachycardia without hypoxia, muffled heart sounds, JVD with Kussmaul’s sign, and 1+ LE edema. The patient was sent to the ED for evaluation of possible pericardial effusion. CTA chest in ED did not demonstrate a PE, but did show bilateral pleural effusions, and a moderate pericardial effusion with evidence of metastatic disease extending into the mediastinum. TTE obtained showing normal LVEF, moderate pericardial effusion with thickened pericardium, and significant respirophasic tricuspid and mitral inflow variations. Pulsus paradoxus was manually checked and found to be 16 mmHg.  Due to concern for cardiac tamponade, she was taken to the cath lab for a RHC and pericardiocentesis. RHC prior to pericardiocentesis showed elevated left and ride sided filling pressures, blunted y decent in the RA, and equalization of diastolic pressures. Pericardiocentesis yielded 200 cc of bloody fluid with improvement, but continued elevation, in her L and R sided pressures. Blunted y decent did give way to a now rapid y descent concerning for constrictive pericarditis. She then underwent a cardiac MRI showing respirophasic septal motion suggestive of interventricular dependence and >1 cm thick pericardium with LGE c/w inflammation. Unfortunately, cytology of pericardial fluid was c/w a malignant effusion and despite treatment with a few months of anti-inflammatory therapy her symptoms did not improve. She then underwent a pericardial stripping with subsequent resolution of her symptoms. As her symptoms and hemodynamics were related to both the effusion and constriction, she was ultimately diagnosed with effusive constrictive pericarditis.  Case Media A B C D E F G H I J K L M N O Click to Enlarge A. ECGB. CXRC-F. TTE (inflow velocities (mitral and tricuspid), IVC sniff test G-L: Right heart catheterization tracings M-N: Post pericardiocentesis TTE: Tissue Doppler O: Cardiac MRI CT Scan TEE – 1 TTE – 2 TTE – 3 TTE -4 CMR -1 CMR – 2 Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case What is cardiac tamponade, what causes it, and how does it lead to hypotension?  The pericardial cavity typically holds 50 cc of fluid, which acts as a lubricant for the beating heart. Accumulation of additional fluid in this space can increase intrapericardial pressure and cause compression of the cardiac chambers. Rapid accumulation of small amounts of fluid can lead to tamponade as the pericardium will not have time to expand. In instances of a slow accumulation, large volumes might accumulate before tamponade occurs as the pericardium will expand to accommodate the fluid.  Many conditions can cause tamponade. The most common are malignancy (>50% of all cases), infection (viral most common, though TB is common in developing countries), trauma/post procedural (e.g. cardiac surgery, pacemaker placement), uremia, rheumatologic (e.g. SLE, RA), drug induced (e.g. hydralazine, procainamide), and radiation-induced. Note the epidemiology is different from causes of pericarditis without tamponade.  Increasing pericardial pressure leads to a compensatory increase in diastolic pressure in all chambers until they become similar to the pericardial pressure. This happens more rapidly in the right side of the heart due to lower diastolic pressures in these chambers. The elevated intracardiac diastolic pressures reduces the driving pressure for filling (Flow = pressure gradient / resistance and so ↓∆P = ↓Flow ); this reduces diastolic filling (preload) and a causes a compensatory increase in contractility and heart rate to maintain stroke volume and cardiac output (CO = HR x SV so as SV decreases, the HR increases). As diastolic filling continues to decrease the transmural distending pressure of the RA and RV will also decrease and eventually lead to diastolic collapse.   As reviewed in previous posts (Mayo and Tennessee), as ventricular interdependence worsens, left ventricular cardiac output can be further compromised and contribute to hypotension. Enjoy Episodes #58 and #59 discussing constrictive pericarditis.  Tamponade can be a difficult clinical diagnosis. How is it diagnosed, what are some of the basic clinical markers of cardiac tamponade, and which are most useful in diagnosis?  Though definitive diagnosis requires pericardiocentesis with hemodynamic and clinical improvement, there are many features that are useful for identifying tamponade. Unfortunately, no one clinical or echocardiographic feature is diagnostic of tamponade and a clinical diagnosis relies on the assimilation of multiple abnormalities.  Beck’s triad of hypotension, jugular venous distension, and muffled heart sounds  Originally described in 1935 by Dr. Claude Beck, it focuses on these signs of tamponade, which were derived from surgical patients and are more characteristic of acute tamponade from trauma or cardiac/aortic rupture. Though ~90% of patients in trauma series have at least one of these findings, only about ~30% have all three. Muffled heart sounds and hypotension are both poorly sensitive findings, making the sensitivity of the overall triad poor.  Tachycardia  Though not specific, tachycardia is a very sensitive marker of cardiac tamponade as in some series it is present in 81-100% of patients with a pooled sensitivity of around 80%.  Elevated JVP  Elevated JVP is one of the key findings in tamponade and is present in almost all cases. Increased early diastolic pressure limits filling during this period, blunting the y descent. Studies show sensitivity ranges from 53-88% with a pooled average of 75%.   Kussmaul’s sign  Kussmaul’s sign is the failure of the JVP to fall during inspiration. This is rarely seen in cardiac tamponade; it is much more common in constrictive pericarditis, where it can be seen in up to 50% of cases.  EKG findings of low voltage or electrical alternans   As fluid builds around the heart it can insulate the heart’s electrical activity from the EKG leads leading to low voltage on the EKG. Additionally, as the heart oscillates within the distended pericardial sack, the QRS amplitude can oscillate, which is called electrical alternans. As low voltage can be seen in a variety of conditions it is poorly specific, but sensitivity is around 70%. Electrical alternans on the other hand is rarely seen in tamponade, but if present it has a PPV > 95%.  Enlarged cardiac silhouette on CXR  The cardiac silhouette on a CXR does not appear enlarged until a pericardial effusion is around 200 mL. Given that many conditions also cause an enlarged silhouette it has both poor sensitivity and specificity.  What is a pulsus paradoxus and what is the pathophysiology? How do you measure it and how clinically useful is it in the diagnosis of tamponade? What conditions might cause it to be absent in tamponade?  In a normal heart, inspiration decreases intrathoracic pressure, thus increasing right-sided filling. As the RV stretches to accommodate the volume, the interventricular septum bulges towards the left causing reduced left-sided filling and therefore a drop in blood pressure (this is ventricular interdependence). During expiration the opposite happens and the blood pressure increases. This process is exaggerated in cardiac tamponade as both ventricles are completing for a limited amount of space, which leads to a larger than normal drop in blood pressure during inspiration. This exaggerated drop is called pulsus paradoxus (though pulsus exaggeratus may be a better name!).   Pulsus paradoxus can be measured with a blood pressure cuff while a patient is breathing normally.  First the cuff is inflated until no Korotkoff sounds can be heard and then slowly deflated until Korotkoff sounds can only be heard during expiration (say 120 mmHg). The cuff is further deflated until sounds can be heard throughout the respiratory cycle (say 100 mmHg). If the difference in these two numbers (here 20 mmHg) is ≥ 10 mmHg it is deemed a clinically significant pulsus paradoxus.  Pulsus paradoxus is an important finding in cardiac tamponade as a pulsus > 10 mmHg occurs in almost all patients with tamponade. A cutoff of 12 mmHg improves specificity and is 98% sensitive and 83% specific in patients with a known pericardial effusion.  There are a few situations where a patient might be in tamponade, but might not have pulsus paradoxus. They include extreme hypotension, low pressure tamponade (e.g., dehydration), atrial septal defects, severe AI, loculated/local effusions, and a very poorly compliant LV or RV.  Pulsus can also be present in patients without pericardial disease, including (but not limited to) patients with COPD or asthma, obstructive sleep apnea, and significant obesity.   What are the signs of cardiac tamponade on echo and RHC?  Echocardiography is the primary imaging modality to evaluate for signs of tamponade. Consistent with the previously described pathophysiology, signs of tamponade on TTE include early diastolic collapse of the RV free wall, diastolic collapse of the RA, swinging of the heart in the pericardial sac, dilated IVC without collapse, a >60% increase in TV flow and >30% decrease in MV flow during inspiration (more specific for tamponade than the cut-offs of 40% and 25% seen in constriction), and septal deviation into the LV with inspiration. Remember to differentiate the size and composition of the effusion. Of these findings early diastolic collapse of the RV free wall is most specific and dilation of the IVC, and late diastolic collapse of the RA are most sensitive.   Though RHC is not routinely performed for the diagnosis of tamponade, there are a few key findings that are relevant. As discussed above, equalization of diastolic pressures, pulsus paradoxus, and pulsus alternans can all be seen on the pressure tracings and measurements in a RHC. Additionally, the RA waveform can show a blunted y descent as discussed above.  What is effusive constrictive pericarditis (ECP) and how does one differentiate it from tamponade or constrictive pericarditis? How is it treated?  Effusive constrictive pericarditis is a clinical entity comprised of both decreased pericardial compliance and a hemodynamically significant pericardial effusion. This is often found when patients undergo pericardiocentesis for suspected tamponade only to reveal continued elevation in RA pressures and constrictive physiology. Some use a cut-off of a failure to fall by 50% or to less than 10 mmHg in the RA.   Though ECP can initially present with some signs of constriction (elevated medial e’ velocities) true constrictive pericarditis should not have signs of a hemodynamically significant effusion (RA/RV diastolic collapse, blunted y descent) and is much less likely to have pulsus paradoxus.  Though there is no uniform consensus on how to treat ECP, it is generally agreed that anti-inflammatory medications are first line. The decision to use NSAIDs or steroids ± colchicine is provider dependent. Prolonged anti-inflammatory therapy may be necessary and escalation versus de-escalation should be guided by symptoms, inflammatory markers, and possibly cardiac MRI. For patients with symptoms refractory to anti-inflammatory medications, pericardiectomy is recommended. Note in effusive-constrictive pericarditis, there tends to be extensive involvement of the visceral pericardium, which requires epicardiectomy, and may need a specialized center.   References Adler, Y., Charron, P., Imazio, M., Badano, L., Barón-Esquivias, G., Bogaert, J., Brucato, A., Gueret, P., Klingel, K., Lionis, C., Maisch, B., Mayosi, B., Pavie, A., Ristić, A. D., Sabaté Tenas, M., Seferovic, P., Swedberg, K., Tomkowski, W., Group, E. S. D., … Nesukay, E. (2015). 2015 ESC Guidelines for the diagnosis and management of pericardial diseasesThe Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal, 36(42), 2921–2964.  Ang, K. P., Nordin, R. B., Lee, S. C. Y., Lee, C. Y., & Lu, H. T. (2019). Diagnostic value of electrocardiogram in cardiac tamponade. The Medical Journal of Malaysia, 74(1), 51–56.  Ariyarajah, V., & Spodick, D. H. (2007). Cardiac Tamponade Revisited. Texas Heart Institute Journal, 34(3), 347–351.  Ayan, M., Siraj, A., & Bhatti, S. (2018). Effusive Constrictive Pericarditis. Journal of the American College of Cardiology, 71(11 Supplement), A2383.  BECK, C. S. (1935). TWO CARDIAC COMPRESSION TRIADS. Journal of the American Medical Association, 104(9), 714–716.  Chiabrando, J. G., Bonaventura, A., Vecchié, A., Wohlford, G. F., Mauro, A. G., Jordan, J. H., Grizzard, J. D., Montecucco, F., Berrocal, D. H., Brucato, A., Imazio, M., & Abbate, A. (2020). Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 75(1), 76–92.  Effusive-Constrictive Pericarditis: Maybe Not as Rare and as Bad as We Thought. (n.d.). American College of Cardiology. Retrieved October 13, 2020, from https://www.acc.org/latest-in-cardiology/articles/2019/04/08/10/42/effusive-constrictive-pericarditis Fowler, N. O. (1993). Cardiac tamponade. A clinical or an echocardiographic diagnosis? Circulation, 87(5), 1738–1741.  Guntheroth, W. G. (2007). Sensitivity and specificity of echocardiographic evidence of tamponade: Implications for ventricular interdependence and pulsus paradoxus. Pediatric Cardiology, 28(5), 358–362.  Jesper K., Poulsen, Steen Hvitfeldt, & Mølgaard, Henning. (n.d.). Cardiac tamponade: A clinical challenge. Retrieved October 13, 2020, from https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-15/Cardiac-tamponade-a-clinical-challenge Kearns, M. J., & Walley, K. R. (2018). Tamponade: Hemodynamic and Echocardiographic Diagnosis. Chest, 153(5), 1266–1275.  Klein, A. L., Abbara, S., Agler, D. A., Appleton, C. P., Asher, C. R., Hoit, B., Hung, J., Garcia, M. J., Kronzon, I., Oh, J. K., Rodriguez, E. R., Schaff, H. V., Schoenhagen, P., Tan, C. D., & White, R. D. (2013). American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: Endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed Tomography. Journal of the American Society of Echocardiography: Official Publication of the American Society of Echocardiography, 26(9), 965-1012.e15. https://doi.org/10.1016/j.echo.2013.06.023  Little William C., & Freeman Gregory L. (2006). Pericardial Disease. Circulation, 113(12), 1622–1632.  McGee, S. R. (2018). Evidence-based physical diagnosis (4th edition). Elsevier.  Pérez-Casares, A., Cesar, S., Brunet-Garcia, L., & Sanchez-de-Toledo, J. (2017). Echocardiographic Evaluation of Pericardial Effusion and Cardiac Tamponade. Frontiers in Pediatrics, 5.  Roy, C. L., Minor, M. A., Brookhart, M. A., & Choudhry, N. K. (2007). Does this patient with a pericardial effusion have cardiac tamponade? JAMA, 297(16), 1810–1818.  Spodick, D. H. (2003). Acute cardiac tamponade. The New England Journal of Medicine, 349(7), 684–690.  Stashko, E., & Meer, J. M. (2020). Cardiac Tamponade. In StatPearls. StatPearls Publishing.  Swami, A., & Spodick, D. H. (2003). Pulsus paradoxus in cardiac tamponade: A pathophysiologic continuum. Clinical Cardiology, 26(5), 215–217.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

Dr. Kim Eagle and Dr. Devraj Sukul discuss a challenging case of Ventricular Septal Rupture after acute MI. Topics include managing complications post-myocardial infarction, the impact of delayed medical care seeking during the pandemic, and the vital role of teamwork in cardiology.

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Connecticut (UCONN) cardiology fellows (Mansour Almnajam, Justice Oranefo, Yasir Adeel, and Srinivas Nadadur) as they enjoy the amazing view from the Heublein tower! They discuss a challenging case of left ventricular free wall rupture & pseudoaneurysm as a complication of a STEMI. Dr. Peter Robinson provides the E-CPR and program director Dr. Joyce Meng provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Bibin Varghese with mentorship from University of Maryland cardiology fellow Karan Desai.    Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his mid 50s with no significant PMH presented with a 10-day history of chest pain that progressed to acute pleuritic pain and shortness of breath in the past 24 hours. On arrival, he was hypothermic, in rapid atrial fibrillation with HR in the 130-150s, and an initial BP was not able to be obtained. He was tachypneic with labored breathing, lethargic, and cyanotic. Exam revealed markedly elevated JVP, cool extremities, and diminished breath sounds with bibasilar rales. Labs demonstrated leukocytosis, significantly elevated liver enzymes, troponin-I at 10.91, elevated NT-proBNP, and lactate at 6. ECG demonstrated tall, broad R-waves in V1-V4 with downsloping STD and upright T-waves concerning for a posterior infarct. He was immediately intubated, cardioverted into NSR, and started on vasopressors. Bedside echocardiogram demonstrated diffuse LV hypokinesis with akinesis of the inferolateral wall, LVEF 25-30%, and pericardial fluid with hyperechoic material adherent to the inferior wall as well as tamponade physiology. Chest CTA was negative for aortic dissection and confirmed hemopericardium. He was taken to the OR where he underwent a subxiphoid pericardial window. They found significant clot burden (both old and new), but no frank rupture. Adherent clot was not removed to prevent further hemodynamic compromise. Intraoperative TEE additionally demonstrated severe eccentric MR with partial posteromedial papillary muscle rupture. An IABP was placed and inotropic and vasoactive support was continued to temporize pending definitive therapy and the patient improved hemodynamically. Repeat TTE prior to surgery demonstrated a large apical and inferolateral pseudoaneurysm. Coronary angiogram revealed proximal occlusion of the LCx and diffuse three vessel coronary disease otherwise. He ultimately underwent CABG, mechanical mitral valve replacement, and pericardial patch repair of the ventricular pseudoaneurysm. Final diagnosis: Free Wall Rupture & Pseudoaneurysm. Thankfully, the patient ultimately made a complete recovery!   Case Media A B C D E F Click to Enlarge A. ECG: tall, broad R-waves in V1-V4 with downsloping STD and upright T-wavesB. CXRC. CT angiogram thoracic aorta: Moderate sized hemopericardium with tamponade physiology. Transmural infarction of LV base to mid inferior wall. Circumflex occlusion just beyond the first obtuse marginal. Normal aorta without dissection or aneurysm.D-F. Coronary angiogram: LCx is occluded proximally, distal vessel fills via faint collaterals from the right, OM1: Fills via right to left collaterals. LAD: 70%, mid; 90%, apical, 1st diagonal: 50%, ostial; 60-70%, proximal; 90% of inferior subdivision, bifurcating vessel. RCA: (Dominant); 50%, mid: 40%, distal. PDA: 60%, proximal, small-caliber vessel. PLV: 60-70%, proximal TEE: Trans-gastric views TEE TEE: MV with color CORS: Occluded Lcx CORS: Obstructive CAD in LAD CORS: RCA TTE: PLA TTE: A4C TTE: A4C with contrast demonstrating an LV pseudoaneurysm Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case This patient presented with EKG showing a posterior myocardial infarction. Why was he not taken to the cath lab immediately for revascularization?  Duration of ischemia, its relationship to infarct size, and the mortality benefit from reperfusion therapies are crucially related to time in the very early course of STEMI. However, this relationship breaks down in patients presenting late after a STEMI.  In OAT (Occluded Artery Trial), hemodynamically stable patients who presented late (3-28 days) after a myocardial infarction with high risk features (e.g., proximal LAD occlusion with TIMI 0 to 1 flow) were randomized to PCI + optimal medical therapy (OMT) within 24 hours or OMT alone. There was no difference in the primary endpoint of all-cause mortality, nonfatal MI, or NYHA class III to IV heart failure. These findings are reflected in the ACC/AHA guidelines, where delayed PCI of a totally occluded infract artery >24 hours after STEMI in hemodynamically and electrically stable patients is given a Class III recommendation (no benefit).   Although the patient presented with EKG findings concerning for a posterior STEMI, this was likely 10 days after his acute insult. In addition, his hemodynamic instability and bedside POCUS raised the concern for a mechanical complication of a STEMI. In a patient with suspected mechanical complication of acute MI, such as free wall rupture and acute MR, the priority of therapy is to rapidly identify the mechanical problem and perform emergency surgical therapy. Furthermore, the need for antiplatelet therapy following any PCI would complicate surgical planning.   PCI may be helpful in patients with ischemia induced papillary muscle dysfunction (“ischemic MR”). However there is no role for immediate PCI when the mechanical integrity of the mitral valve has been compromised.  This patient presented with hemodynamic instability and bedside POCUS revealed pericardial fluid with tamponade physiology. What are some causes of acute hemorrhagic pericardial effusion?  When thinking about hemorrhagic pericardial effusions, expedited evaluation is critical. While there is overlap with traditional causes of pericardial effusion, some causes may need immediate intervention. Amongst these considerations are iatrogenic complication of cardiac surgery, cardiac catheterization, or electrophysiologic procedures. Other etiologies include complications of myocardial infarction including free wall rupture/pseudoaneurysm, complication of aortic dissection, and trauma. As with serous pericardial effusions, malignancy should remain on the differential, as well as tuberculosis in endemic areas.   A CTA of the aorta ruled out dissection but showed a moderate sized hemopericardium raising concern for a mechanical complication of posterior MI, specifically a free wall rupture (FWR). What are the risk factors for a FWR after an MI?  Ventricular free wall rupture is quite uncommon in the reperfusion era; however, if it does occur, mortality rates are high. FWR typically occurs acutely or sub-acutely, occurring within 2 weeks for 90% of patients. Risk factors include first myocardial infarction, poor collateralization of the infarcted territory, older age, female sex, persistent ST elevation and delayed presentation/unsuccessful revascularization. When patients present acutely, patients will typically develop tamponade, rapidly progress to pulseless electrical activity, and/or  sudden cardiac death. When patients develop subacute FWR or contained rupture (i.e., pseudoaneurysm), they may present with signs and symptoms of pericarditis and subacute hypotension.  When FWR occurs, it typically involves the anterior, posterior, or lateral left ventricular wall. The pathophysiology of ventricular free wall rupture is related to the timing of the rupture. Rupture will typically occur at the border of the necrotic and healthy (and often hyperkinetic) myocardium and in areas of the greatest shear stress. In the left ventricle, this tends to be near the anterior and posterior papillary muscles, regardless if they are compromised in the infarct.  Note, pericardial effusions can be a common finding in the setting of an acute MI (~15-25% of patients in the acute setting); however, a rapidly expanding pericardial effusion associated with significant wall thinning along the infarcted region should raise the suspicion for LV free wall rupture.   The patient was stabilized after surgical evacuation of pericardial fluid in the OR. When should you consider pericardiocentesis vs surgical management?  In cases of cardiac tamponade with concern for circulatory collapse there are no absolute contraindications to pericardiocentesis. The goal is urgent drainage of pericardial fluid and how we drain the fluid will depend on the etiology, acuity, and available providers. Emergent surgical management should generally be considered first line in patients with traumatic hemopericardium, aortic dissection related hemopericardium, or free wall rupture. In the setting of aortic dissection, controlled drainage of very small amounts of hemopericardium can be considered as a temporizing measure to maintain SBP > 90 mmHg. With purulent or loculated effusions, surgical drainage over pericardiocentesis may be the preference as well.   Supportive measures include ensuring adequate preload, avoiding diuretics and/or vasodilator therapy, and inotropic and vasopressor therapy as needed.   The patient was found to have a pseudoaneurysm rather than a frank free wall rupture. What is a pseudoaneurysm and how is it different than a true ventricular aneurysm?  Ventricular pseudoaneurysm is caused by a contained rupture of the LV free wall where the rupture is contained by adherent pericardium, thrombus, or hematoma with no myocardial tissue in the outpouching. In a true ventricular aneurysm, the outer walls are formed by the infarcted myocardium and scar tissue. Pseudoaneurysms have a high propensity to rupture and thus surgical management is recommended.   A small, narrow neck typically connects the ventricular cavity with the contained pericardial space. On echocardiogram, pseudoaneurysm can demonstrated the following differentiating features: (1) neck diameter to maximal aneurysmal diameter < 0.5; (2) color and spectral doppler demonstrating bidirectional flow through the narrowed neck; (3) thrombus and/or spontaneous echo contrast in the pericardial space.   References Alkhalil Mohammad, Choudhury Robin P. Reperfusion Treatment in Late Presentation Acute Myocardial Infarction. Circ Cardiovasc Interv. 2018;11(9):e007287. doi:10.1161/CIRCINTERVENTIONS.118.007287  Hochman JS, Lamas GA, Buller CE, et al. Coronary Intervention for Persistent Occlusion after Myocardial Infarction. N Engl J Med. 2006;355(23):2395-2407. doi:10.1056/NEJMoa066139  Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseasesThe Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. doi:10.1093/eurheartj/ehv318  Hutchins KD, Skurnick J, Lavenhar M, Natarajan GA. Cardiac rupture in acute myocardial infarction: a reassessment. Am J Forensic Med Pathol. 2002 Mar;23(1):78-82. doi: 10.1097/00000433-200203000-00017. PMID: 11953501.  Griffin, Brian P. 2019. Manual of cardiovascular medicine.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join University of California San Diego (UCSD) cardiology fellows (Harpreet Bhatia, Dan Mangels, and Quan Bui) for a relaxing beach bonfire in the beautiful city of San Diego! They discuss a challenging case of post-transplant cardiac allograft vasculopathy. Dr. Hao (Howie) Tran provides the E-CPR and program director Dr. Daniel Blanchard provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Richard Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his late 20s with a past medical history of orthotopic heart transplant, presents with one-week of progressive lower extremity edema and dyspnea with NYHA class IV symptoms. 5 years prior, he underwent orthotopic heart transplant for arrhythmogenic right ventricular cardiomyopathy. Subsequently, he has had multiple episodes of rejection or recurrent graft dysfunction. On presentation, he was normotensive and borderline tachycardic. Exam revealed elevated JVP, decreased breath sounds, and pitting edema.  Labs demonstrated leukocytosis, acute kidney injury, and elevated pro-BNP. TTE demonstrated LVEF 35%, apical akinesis, and grade III diastolic dysfunction (all similar to prior). He was initially diuresed and RHC/EMB was performed to evaluate for rejection. Early in his course, the patient unfortunately suffered a PEA arrest with ROSC was quickly achieved after 1 minute of CPR. He was intubated and cannulated for VA ECMO. EMB demonstrated ISHLT Grade 1R cellular rejection and he was ultimately listed for re-transplant. Shortly thereafter, the patient received an OHT. His pathology demonstrated intimal thickening of all his coronaries, consistent with coronary artery vasculopathy, felt to be the major contributor to his presentation.   Case Media ECG Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. What is CAV?   CAV stands for cardiac allograft vasculopathy. Within the transplanted heart, CAV is the proliferation of vascular smooth muscle and intimal thickening in the epicardial coronary arteries and microvasculature leading to diffuse narrowing. CAV is common, present in greater than 30% of patients at 5 years post-transplant. It is a significant contributor to post-transplant mortality after the first year.   CAV, in contrast to typical atherosclerotic lesions, is diffuse and concentric while atherosclerosis tends to be focal with eccentric luminal narrowing and heterogenous plaque composition. Patients s/p OHT can still develop typical coronary artery disease, likely developed from pre-existing disease in the donor heart. CAV should be high on the differential for the cause of graft dysfunction, especially after the first year post-transplant.   2. How and Why Does CAV Occur?  CAV has multiple contributing factors. There are immunologic and non-immunologic factors, but it appears the immunologic components play the larger role given that the pan-vasculopathy develops in the donor heart and not in the recipient’s vasculature. In CAV, there is chronic immune-mediated injury creating a persistent inflammatory state in the donor coronary endothelium leading to a neointimal proliferative process in the coronaries. Amongst immunologic factors, it appears the number of episodes of cellular rejection correlates with the development of CAV.   CAV occurs when foreign antigens are recognized by the host immune system as “non-self,” a process termed allorecognition.  T-cells are subsequently activated, and release a number of inflammatory cytokines that leads to additional T-cell stimulation, inflammatory cell proliferation, and endothelial cell propagation.  Ultimately this inflammatory cascade leads to smooth muscle cell advancement and intimal growth into the arterial lumen.   Other immunologic factors include HLA mismatch and antibody-mediated rejection. There are numerous non-immunologic factors, including older donor age, CMV infection, hyperlipidemia, insulin resistance, donor brain death secondary to intracranial hemorrhage, and prolonged ischemic time.   3. How Do Patients with CAV Present?   Donor hearts are denervated at explantation, and so post-transplant patients typically will not develop classic anginal symptoms as seen with typical atherosclerotic coronary disease. Thus, routine surveillance is necessary (see below).   If not diagnosed early, the clinical presentation may include LV dysfunction (with or without symptoms), acute myocardial infarction, heart block, arrhythmias, syncope, or sudden cardiac death.   4.  How Do We Diagnose CAV?  Routine surveillance is necessary because patients are generally asymptomatic and there is a high incidence of CAV posttransplant.   The most common method for screening includes coronary angiography, but its sensitivity is reduced compared to traditional atherosclerotic disease as CAV is diffuse. Intravascular ultrasound (IVUS) significantly improves sensitivity and the early the detection of disease.   The timing and method of screening will be center-specific. As the patient is farther removed from their transplant date, dobutamine stress echo may be a reasonable method to screen for CAV. Myocardial perfusion imaging, specifically with PET Rest/Stress with absolute myocardial blood flow quantification, and coronary CTA may also be effective methods to diagnose CAV.   The ISHLT grading of CAV by angiography is as follows:  CAV0 (Nonsignificant): No detectable angiographic lesion  CAV1 (mild): Angiographic LM lesion <50%; or primary vessel with maximum lesion of <70%; or any branch vessel stenosis <70% without allograft dysfunction  CAV2 (moderate): Angiographic LM <50%; or a single primary vessel ≥70% stenosis; or isolated branch stenosis in 2 systems ≥ 70% without allograft dysfunction  CAV3 (Severe): Angiographic LM ≥50%; or ≥2 primary vessel ≥70% stenosis; or isolated branch stenosis in all 3 systems ≥70%; CAV1 or CAV2 with allograft dysfunction or evidence of significant restrictive physiology  5. How Do we Treat CAV?   Primary prevention remains key. Statins have been shown prospectively to reduce cardiac allograft vasculopathy and improve survival. Chronic immunosuppression is the foundation of post-transplant care. The mTOR inhibitors, everolimus and sirolimus, harbor antiproliferative properties that may prevent allograft vasculopathy. However, these are generally not first-line immunosuppressive medications in the United States, given the potential for multiple side effects including impaired wound healing in new transplant patients. In patients with documented or progressive CAV, escalation of immunosuppression to sirolimus may be considered. Revascularization for patients may be considered, given the morbidity associated with CAV, though no survival advantage has been shown. In patients with severe CAV, re-transplantation should be considered.   References Mehra, M. R., Crespo-Leiro, M. G., Dipchand, A., et. al (2010). International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy—2010.  Chih, S., Chong, A. Y., Mielniczuk, L. M. et. al. (2016). Allograft vasculopathy: the Achilles’ heel of heart transplantation. Journal of the American College of Cardiology, 68(1), 80-91.  Schmauss, D., & Weis, M. (2008). Cardiac allograft vasculopathy: recent developments. Circulation, 117(16), 2131-2141.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Virginia Commonwealth University (VCU) cardiology fellows (Ajay Pillai, Amar Doshi, and Anna Tomdio) for a delicious skillet breakfast and amazing day in Richmond, VA! They discuss a fascinating case of a patient with Wolff-Parkinson-White (WPW) and hypertrophic cardiomyopathy (HCM). Dr. Keyur Shah provides the E-CPR and program director Dr. Gautham Kalahasty provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai. Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his mid-60s presented to the ED after an episode of unwitnessed syncope while drinking. Patient had suddenly passed out from a seated position with no prodrome or post-ictal state. He had episodes like this in the past, which were thought to be seizures, but otherwise PMHx only notable for alcohol use disorder. He denied any FH of SCD or syncope. In the ED, exam was unremarkable. Labs notable for mild thrombocytopenia, mild hyponatremia with AKI, 2:1 AST/ALT ratio, elevated NT-proBNP, and a very high lactate that rapidly corrected with fluids. EKG was notable for sinus tachycardia, short PR interval, wide QRS, and delta waves consistent with Wolff-Parkinson-White (WPW) pattern. Echo showed preserved LVEF, thickened LV septum (1.6 cm) and posterior wall (1.3 cm) concerning for hypertrophic cardiomyopathy (HCM). No outflow tract gradient was noted at rest or with stress, and the strain pattern demonstrated apical sparing. Evaluation for cardiac amyloid, including plasma cell dyscrasia and PYP scan, was negative. Cardiac MRI confirmed severely thickened LV inferior and inferolateral walls at 1.7 cm with no LVOT obstruction. 25% of the myocardium demonstrated patchy LGE.   Due to concern for WPW syndrome, the patient underwent an EP study. This revealed a malignant septal accessory pathway that was successfully ablated with resolution of the WPW EKG features. Given large LGE burden in setting of HCM, patient underwent placement of primary prevention ICD. Genetic testing for PRKAG2 mutation is pending given comorbid WPW and HCM.  Case Media A E C D B F Click to Enlarge A. CXR: Slightly increased interstitial markings in the lung bases, an elevated right hemidiaphragm. No acute airspace disease or pulmonary edemaB. ECG: Sinus tachycardia rate 120bpm, PR interval 80ms, QRS 130ms, WPW pattern.  Arruda algorithm localizes to posterior septum.C. CMR:  Myocardium nulls before blood pool.D. CMR:  Delayed gadolinium enhancementE. Follow up ECG: NSR 78, repolarization abnormalities.  T wave memory inferior leads.F. CXR status post dual chamber ICD implantation TTE: Apical 4 chamber TTE: Apical 2 chamber TTE: Apical 3 chamber TTE: Strain imaging CMR: 4 chamber cine CMR: 2 chamber cine CMR: 3 chamber cine CMR: Short axis cine at base level CMR: Short axis cine at mid-papillary level CMR: Short axis cine at apical level Episode Schematics & Teaching Hypertrophic Cardiomyopathy Infographic Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case Our patient was found to have Wolff-Parkinson-White (WPW) pattern. What are the diagnostic criteria for WPW pattern and how does it differ from WPW syndrome? How can you localize the accessory pathway using the EKG?  WPW pattern refers to the presence of the below criteria on a patient’s surface EKG in the absence of symptomatic arrhythmias. If symptomatic arrhythmias related to the accessory pathway occur, then it is WPW syndrome. Symptoms may include palpitations, shortness of breath, presyncope, syncope, and sudden cardiac death (SCD).   Not all patients with accessory pathways have EKG findings as only 60-75% of accessory pathways are “manifest” (meaning they conduct antegrade from atria to ventricles or are bidirectional). Conversely, a “concealed” accessory pathway only conducts retrograde (from ventricles to atria) and would not be apparent on resting sinus EKG; these patients can have WPW diagnosed after a ventricular premature beat, ventricular pacing, or an EP study that shows retrograde conduction through the accessory pathway.   The WPW pattern is diagnosed by the following EKG criteria:  Short PR interval < 120 ms  Signs of pre-excitation: a delta wave (slurred upstroke of QRS complex) and QRS > 120 ms. The degree of pre-excitation on EKG depends on the position (how much of the ventricular myocardium is depolarized by the accessory pathway) and depolarization speed of the accessory pathway (more rapid conduction leading to earlier ventricular depolarization and wider delta wave).   We can use EKG findings to localize accessory pathways using the Arruda Criteria, which has an overall sensitivity of 90% and specificity of 99%. Note, patients who have a left-lateral bypass tract as the antegrade limb may not have delta waves on surface EKG, as the atrial impulse can take longer to reach the bypass tract than the AV node.    What are the major mechanisms for WPW and how do they lead to early activation of the ventricles? How can this precipitate arrhythmias?  Accessory pathways are abnormal congenital connections between the atria and ventricles when there is incomplete atrio-ventricular isolation during fetal development. They can be associated with congenital cardiac malformations like Ebstein anomaly.  Depolarization of the ventricles occurs via the AV node and the accessory pathway simultaneously, leading to early depolarization of a portion of the ventricles and the characteristic delta wave. Depolarization through the His Purkinje system reaches the apex first and travels back up the ventricle, meeting the slower cell to cell conduction from the accessory pathway and causing termination of the impulses. The resulting QRS complex is essentially a “fusion beat” between the two sources.  Accessory pathways often have more rapid conduction, but longer refractory periods than the AV node. If a PAC occurs when the accessory pathway is refractory, there will be antegrade conduction solely through the AV node. As the impulse travels through the ventricles it can conduct retrograde through the accessory pathway from V to A. This creates a reentrant pathway that results in atrioventricular reentrant tachycardia (AVRT), which accounts for up to 80% of SVT in WPW. Orthodromic AVRT (antegrade through AV node, retrograde through accessory pathway) accounts for 90-95% of AVRT in WPW.   Other tachycardias can occur where the accessory pathway is a bystander and not required for initiation and maintenance of the arrhythmia like in AVRT. This includes atrial arrhythmias (e.g., atrial fibrillation, atrial flutter), ventricular tachycardia, and ventricular fibrillation. Atrial fibrillation is relatively common (~20%) in WPW syndrome patients. Atrial fibrillation with an accessory pathway can produce rapid ventricular rates due to unencumbered conduction via the accessory pathway. In these situations, QRS width and morphology may vary due to variable conduction via the AV node vs accessory pathway. Depending on the rate of conduction, the patient can degenerate into VF. A shorter refractory period places patients at the highest risk for VF.   How do we risk stratify patients with WPW pattern? When would an EP study (EPS) be beneficial? What features are high risk on EPS and would warrant treatment?  Patients who are asymptomatic are typically at low risk of sudden cardiac death. Those who do have SCD typically have symptoms at some point prior to arrest. Patients with intermittent loss of the delta wave on a beat-to-beat basis are likely at lower risk, as it suggests the accessory pathway lacks the ability for rapid AV conduction. However, persistent delta wave in asymptomatic patients may still be at low risk.   The risk for SCD is thought to be due to rapid conduction of Afib down the accessory pathway leading to VF. Accessory pathways with shorter refractory periods are able to conduct at higher rates (shorter R to R intervals). Delta waves disappear when R to R interval is less than the refractory period, at which point the atrial impulse only conducts through AV node. Thus, the lower the HR that delta waves become intermittent, the lower the risk of SCD.  We can start risk stratification in most patients noninvasively with a resting EKG and exercise EKG stress test, unless we clearly demonstrate intermittent delta wave at rest. If preexcitation persists even with maximal sinus heart rates, then an EPS is recommended.   High risk features on EPS include multiple accessory pathways, inducible AVRT or Afib, shortest pre-excited RR interval (SPERRI) < 250 ms, and accessory pathway refractory period < 240 ms  How are high risk WPW pattern and WPW syndrome treated?  For the chronic prevention of arrhythmia:  In patients with high risk WPW pattern, we typically refer for catheter ablation (typically radiofrequency ablation though cryoablation can be utilized) of the accessory pathway to help prevent SCD. Successful ablation is curative.   In patients with WPW syndrome, we can still risk stratify with the above algorithm, but symptomatic patients should receive treatment. Ablation is first line for all patients who are candidates and willing given success rates of 90-95%.  In terms of medical therapy for patients who are not ablation candidates, flecainide and propafenone are reasonable options in the absence of structural heart disease. Dofetilide or sotalol are options in patients with structural heart disease. AV nodal blocking agents can be considered in the setting of orthodromic AVRT.  For WPW patients presenting with an acute arrhythmia and who are hemodynamically unstable, synchronized cardioversion is first line therapy. Pharmacologic therapy in the hemodynamically stable patient depends on the suspected level of involvement of the accessory pathway and type of arrhythmia. For arrhythmias not dependent on the accessory pathway for initiation and maintenance (e.g., atrial fibrillation), AV nodal blocking agents can induce rapid antegrade conduction down the accessory pathway which could degenerate into ventricular fibrillation. In the setting of rapid pre-excited atrial fibrillation, procainamide or ibutilide are the agents of choice.   AVRT requires the accessory pathway for initiation and maintenance of the arrhythmia. Orthodromic AVRT will typically be a narrow complex tachycardia (unless there is aberrancy) and can be managed similarly to other regular narrow complex tachycardias (e.g., use of adenosine). If there is any doubt about the diagnosis, procainamide should be utilized.    Where do the diagnostic schema for WPW and HCM overlap and what syndrome should you think of in patients where they coexist?  Familial WPW is rare and characterized by the autosomal dominant inheritance of the combination of WPW syndrome and non-sarcomeric HCM. It is caused by mutations in the PRKAG2 gene, which encodes a portion of 5’AMP-activated protein kinase (AMPK). This mutation leads to cardiac glycogen overload, resulting in ventricular hypertrophy (HCM phenocopy), WPW-like syndrome, AV block, and progressive conduction system disease.   Cardiac myocyte glycogen accumulation is thought to decrease the myocardial activation threshold and so overcomes the insulating properties of the AV annulus fibrosus, resulting in electrical leak between the atria and ventricles. This gives the clinical appearance of an accessory pathway. Given the typical absence of a distinct accessory pathway, EPS with ablation is often not effective.   Other glycogen storage disorders may cause a similar overlap between an HCM phenocopy and WPW mimic like Pompe disease and Danon disease.  References Aggarwal, V., Dobrolet, N., Fishberger, S., Zablah, J., Jayakar, P., & Ammous, Z. (2015). PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis. Annals of Pediatric Cardiology, 8(2), 153.  Arruda, M. S., McCLELLAND, J. H., Wang, X., Beckman, K. J., Widman, L. E., Gonzalez, M. D., Nakagawa, H., Lazzara, R., & Jackman, W. M. (1998). Development and Validation of an ECG Algorithm for Identifying Accessory Pathway Ablation Site in Wolff-Parkinson-White Syndrome. Journal of Cardiovascular Electrophysiology, 9(1), 2–12.  Calkins Hugh, Yong Patrick, Miller John M., Olshansky Brian, Carlson Mark, Saul J. Philip, Huang Shoei K. Stephen, Liem L. Bing, Klein Lawrence S., Moser Suzan A., Bloch Daniel A., Gillette Paul, & Prystowsky Eric. (1999). Catheter Ablation of Accessory Pathways, Atrioventricular Nodal Reentrant Tachycardia, and the Atrioventricular Junction. Circulation, 99(2), 262–270.  Chhabra, L., Goyal, A., & Benham, M. D. (2020). Wolff Parkinson White Syndrome (WPW). In StatPearls. StatPearls Publishing.  Gollob, M. H., Green, M. S., Tang, A. S.-L., Gollob, T., Karibe, A., Hassan, A.-S., Ahmad, F., Lozado, R., Shah, G., Fananapazir, L., Bachinski, L. L., Tapscott, T., Gonzales, O., Begley, D., Mohiddin, S., & Roberts, R. (2001). Identification of a Gene Responsible for Familial Wolff–Parkinson–White Syndrome. New England Journal of Medicine, 344(24), 1823–1831.  Gollob Michael H., Seger John J., Gollob Tanya N., Tapscott Terry, Gonzales Oscar, Bachinski Linda, & Roberts Robert. (2001). Novel PRKAG2 Mutation Responsible for the Genetic Syndrome of Ventricular Preexcitation and Conduction System Disease With Childhood Onset and Absence of Cardiac Hypertrophy. Circulation, 104(25), 3030–3033.  Miyamoto, L. (2018). Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome. The Journal of Medical Investigation: JMI, 65(1.2), 1–8.  Page, R. L., Joglar, J. A., Caldwell, M. A., Calkins, H., Conti, J. B., Deal, B. J., Estes III, N. A. M., Field, M. E., Goldberger, Z. D., Hammill, S. C., Indik, J. H., Lindsay, B. D., Olshansky, B., Russo, A. M., Shen, W.-K., Tracy, C. M., & Al-Khatib, S. M. (2016). 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia. Heart Rhythm, 13(4), e136–e221.  Spector, P., Reynolds, M. R., Calkins, H., Sondhi, M., Xu, Y., Martin, A., Williams, C. J., & Sledge, I. (2009). Meta-Analysis of Ablation of Atrial Flutter and Supraventricular Tachycardia†. American Journal of Cardiology, 104(5), 671–677. Talle, M. A., Buba, F., Bonny, A., & Baba, M. M. (2019). Hypertrophic Cardiomyopathy and Wolff-Parkinson-White Syndrome in a Young African Soldier with Recurrent Syncope. Case Reports in Cardiology, 2019.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Baylor College of Medicine cardiology fellows (Khurrum Khan, John Suffredini, and Aliza Hussain) during restaurant week in Houston! They discuss an interesting case of STEMI in a patient with a recent diagnosis of e-cigarette or vaping product use-associated lung injury (EVALI). Dr. Vijay Nambi provides the E-CPR and APD Dr. Arunima Misra provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Bibin Varghese with mentorship from University of Maryland cardiology fellow Karan Desai.    Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A male in his mid 40s with a 30 pack year smoking history, EVALI (e-cigarette and vaping associated lung injury), and asthma presented with dyspnea and persistent chest pain. He had been vaping for the past year. One month prior , CT chest showed bilateral patchy infiltrates and he was diagnosed with EVALI and started on a steroid taper with resolution of his CT abnormalities. A nuclear stress test at that time was negative for ischemia. On arrival, he was in sinus tachycardia, normotensive, and not on oxygen supplementation. Physical exam was negative for volume overload or heart murmurs. EKG showed new Q waves with STE in V2-V4, with associated Q waves and TWI in the lateral leads and troponin returned moderately elevated. He was emergently taken to the cath lab which showed an abrupt cutoff of flow to the LAD. He received a single DES with resolution of coronary flow. A post-cath TTE showed an LVEF of 40-45% with apical anterior and anteroseptal WMA. He was monitored in the CCU the next day and he was treated with aspirin, ticagrelor, ACEi, metoprolol succinate and high intensity statin and subsequently discharged in stable condition with cardiac rehab follow-up. Case Media A B Click to Enlarge A. Presentation ECG (Anterior STEMI) B. Baseline ECG LAD occlusion Post PCI RCA TTE 1 TTE 2 TTE 3 Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. The patient presented with a STEMI following a diagnosis of EVALI. What is known about the cardiovascular risks of vaping and e-cigarette use?  The overall cardiovascular risks of e-cigarette use remains to be elucidated  In preclinical studies, e-cigarettes use have been linked to increased sympathetic activity, oxidative stress, endothelial dysfunction, vascular injury, and altered platelet activity  One observational study has suggested that daily e-cigarette users were 1.79 times more likely to experience MI than individuals who had never used e-cigarettes.  Additional high-quality randomized controlled trials are needed to conclusively establish the safety and efficacy of e-cigarettes.  2. So the data is still emerging regarding the overall cardiovascular risks of e-cigarette use. Of note, the patient had a negative stress test a month prior. Should that not translate into low likelihood of cardiovascular events?  Remember that stress testing for the diagnosis of obstructive coronary disease is most helpful in patients with an intermediate pretest probability for coronary artery disease. Further myocardial ischemia can occur not only secondary to obstructive epicardial disease (which may be new and acute from plaque rupture/erosion), but also from microvascular disease, vasospastic disease, and so forth. Stress testing with radionuclide myocardial perfusion imaging (e.g., SPECT, PET) is a well-established method for assessing coronary disease, but it is not an anatomic assessment. With nuclear stress tests, the causes of a false-negative result could include submaximal exercise (if doing exercise stress), collateral or overlapping epicardial circulation, suboptimal images (including artifact and poorly timed stress images), inaccurate interpretation, and balanced ischemia.   Nonetheless, sensitivity for obstructive CAD in SPECT approaches 85-90% with specificity around 70-75%. As SPECT imaging is not an anatomic assessment, a recent negative nuclear stress test does not necessarily mean very low risk for future major adverse cardiovascular events. Even with a normal nuclear stress test, there is a 0.65% – 1.78% annual event rate of death or non-fatal MI.   3. Can non-obstructive and potentially “vulnerable” plaque be detected before an event?  Remember ECG, echocardiographic and radionuclide stress testing are different modalities to assess for obstructive CAD after inducing ischemia via exercise or medications. These modalities typically assess for flow-limiting lesions (e.g., typically greater than 50%). However, acute coronary syndrome can occur subsequently from lesions that were not initially obstructive.   In the PROSPECT study looking at patients who presented with ACS and underwent PCI to the culprit lesion and were followed afterward for ~ 3 years for adverse events, recurrent major adverse plaque rupture events were noted equally at the culprit lesion and at non-culprit lesions. Non-culprit lesions that were responsible for unanticipated events were angiographically mild on initial evaluation, had thin-cap fibroatheromas, or had large plaque burden as determined by gray-scale and radiofrequency intravascular ultrasound.  This is where coronary CTA has an increasingly larger role. A study looking at coronary CTA determined that plaques with positive remodeling and low attenuation features were at higher risk of ACS developing over time. Those individuals with neither of those features had high NPV in ruling out future ACS events. Typically, as a lesion increases in size, it can compromise luminal blood flow when 50% or greater narrowing of the lumen is observed (remember this is slightly different than labeling a lesion as “obstructive” to the point of potentially necessitating intervention). However, when there is an absence of luminal loss regardless of lesion size in early lesions, this is called “positive coronary artery remodeling” and there is compensatory enlargement of the epicardial vessel. Post-mortem studies have found that vessels with positive remodeling have been associated with increased lipid content, as well as features associated with unstable plaque (e.g., thin-cap fibroatheroma).   4.  The patient had an MI at age 45! Apart from e-cigarette use, what other evaluation is warranted in a young patient with ACS or STEMI?  Traditional risk factors such as dyslipidemia, T2DM, HTN, and family history of premature CAD must be evaluated as plaque rupture events are still the most common cause of MI in young patients (age < 45 years). Furthermore, the differential for young individuals presenting with acute myocardial infarction should include non-atherosclerotic causes such as: anomalous coronary artery, spontaneous coronary artery dissection, coronary embolus, coronary vasculitis, coronary aneurysm (all of which have been discussed in the @cardionerds #CNCR episodes!).   If thrombus is present on angiography without traditional risk factors, workup should include evaluation for hypercoagulable states (e.g., Protein C and S deficiency, Factor V Leiden, APLS) or evaluating for a source of embolism (e.g., Afib, valvular lesion, LV thrombus, or even PFO [Enjoy Ep #51 – ACS & PFO]). Coronary thrombus may arise in situ from plaque rupture/erosion or as an embolus; recall that coronary emboli may be categorized as: direct, paradoxical, or iatrogenic.  Angiographic and multi-modal imaging findings may reveal the underlying etiology, including SCAD (Enjoy Ep #65 – SCAD), or one of the other non-atherosclerotic coronary processes listed above. If no obvious lesion is present, one should evaluate for Myocardial Infarction with non-obstructive coronaries (MINOCA) such as coronary vasospasm, and coronary microvascular dysfunction  Other considerations in young patients should include drug use, such as cocaine and methamphetamine use. Furthermore, oral contraceptives combined with another pro-thrombotic risk factor (e.g., tobacco use) may lead to acute myocardial infarction.   5.  Sounds like the patient improved symptomatically after PCI placement. Going back to the basics, why do we obtain a TTE after STEMI and monitor in the CCU?    Assessment of resting LV function helps us risk stratify patients, as it is one of the strongest predictors of survival. Furthermore, it will help us guide our medical therapy after STEMI. Echocardiographic evaluation can also help us characterize any suspected mechanical complications of STEMI. Beyond just survival, residual LV systolic function is one of the strongest predictors of sudden cardiac death risk after STEMI. Patients with an initially reduced LV function (e.g., <40%), who do not warrant ICD therapy before discharge, should undergo re-assessment of LV function >40 days after the index event to assess eligibility for ICD therapy. The delay to ICD therapy in this circumstance comes from the results of the DINAMIT trial in which ICD therapy 6 to 40 days after MI in patients with LVEF  ≤ 35% was not shown to reduce overall cardiac death risk.   The cardiac intensive care unit was initially established as a separate ward for the early detection and treatment of arrhythmias following acute myocardial infarction. Monitoring for arrhythmia in the CCU remains a cornerstone of post-STEMI management, as well as mechanical, embolic and inflammatory complications.   Mechanical complications after a STEMI include LV failure and cardiogenic shock, acute severe mitral regurgitation from papillary muscle rupture, ventricular septal rupture, LV free wall rupture, ventricular pseudoaneurysm, and ventricular aneurysm.   LV mural thrombus can cause an embolic complication, especially after a large anterior wall MI and delayed reperfusion.   Inflammatory complications include early and late pericarditis (i.e. Dressler’s syndrome – though this is rarely seen).  References Buchanan, N. D. et al. Cardiovascular risk of electronic cigarettes: a review of preclinical and clinical studies. Cardiovasc. Res. 116, 40–50 (2020).  Hachamovitch, R. et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation 97, 535–543 (1998).  Arbab-Zadeh, A. Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm. Heart Int. 7, (2012).  Falk Erling, Shah Prediman K. & Fuster Valentin. Coronary Plaque Disruption. Circulation 92, 657–671 (1995).  Motoyama, S. et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J. Am. Coll. Cardiol. 54, 49–57 (2009).  Stone, G. W. et al. A Prospective Natural-History Study of Coronary Atherosclerosis. N. Engl. J. Med. 364, 226–235 (2011).  Gulati, R. et al. Acute Myocardial Infarction in Young Individuals. Mayo Clin. Proc. 95, 136–156 (2020).  O’Gara, P. T. et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. J. Am. Coll. Cardiol. 61, e78–e140 (2013).  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD