Cardionerds: A Cardiology Podcast

In this episode, CardioNerds co-founder Amit Goyal joins Dr. Iva Minga, Dr. Kevin Lee, and Dr. Juan Pablo Salazar Adum from the University of Chicago – Northshore in Evanston, IL to discuss a case of primary cardiac diffuse large B-cell lymphoma. The ECPR for this episode is provided by Dr. Amit Pursnani (Advanced Cardiac Imaging, Fellowship program director, NorthShore University HealthSystem). Audio editing by CardioNerds Academy Intern, Dr. Akiva Rosenzveig. Case synopsis: A 77-year-old man with no significant medical history presents to the emergency department with progressive shortness of breath for 1 week. He reports an unintentional 15-pound weight loss in the prior month as well as constipation and abdominal/flank pain. On examination he was found to be tachycardic with a regular rhythm and further evaluation with a chest X-ray and chest CT scan demonstrated a large pericardial effusion. This was further investigated with an urgent echocardiogram that revealed a large pericardial effusion with a large mass attached to the pericardial side of the RV free wall, as well as signs of early cardiac tamponade. A pericardiocentesis was performed and 550mL of bloody fluid was withdrawn. The fluid was sent for laboratory analysis and cytology. A cardiac MRI demonstrated a large invasive mass in the pericardium and RV wall consistent with cardiac lymphoma. Cytology confirmed diffuse large B-cell lymphoma. Subsequent CT and PET scans did not find any other site of malignancy, giving the patient a diagnosis of primary cardiac diffuse large B-cell lymphoma. The patient underwent R-CHOP chemotherapy and was followed closely with repeat cardiac MRI and PET scans which demonstrated resolution of the cardiac mass at his one-year surveillance follow-up. This case was published in US Cardiology Review, the official journal of CardioNerds. To learn more, access the case report article here. “To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine. CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ). Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls – A Mystery Mass in the Heart – Cardiac Lymphoma The most common cause of malignant cardiac masses is metastasis. Primary cardiac tumors are rare. Cardiac tumors are separated into 2 categories: benign and malignant. They are often differentiated based on their location and their degree of tissue invasion. Multimodality imaging is essential in the diagnosis, management, and surveillance of cardiac masses. A multidisciplinary team approach is invaluable for management of patients with cardiac tumors. Show Notes – A Mystery Mass in the Heart – Cardiac Lymphoma 1. What is the clinical presentation of cardiac masses? Cardiac masses can have a variable presentation. They can present with arrhythmias, angina, heart failure symptoms, or pericardial effusion. Patients can also be asymptomatic; the masses can be found incidentally on cardiac or chest imagining. 2. What is the differential diagnosis for cardiac masses? Cardiac masses are separated into benign and malignant. The most common malignant cardiac masses are metastases from a distant source. The location of the mass is important in narrowing the differential. 3. What imaging modalities are used to diagnose cardiac masses? Multimodality imaging is needed to describe the mass in detail and guide diagnosis. An echocardiogram is usually the first imaging modality. Cardiac MRI is a great modality that allows for the detailed visualization as well as tissue characterization of the mass. Cardiac CT, chest CT, and PET scans are also imagining modalities that can be used in the management of the mass. 4. How do you manage cardiac masses? Management of cardiac masses depends on etiology (benign or malignant) and the associated hemodynamic changes associated with it. For example, if a benign cardiac mass is associated with significant valvular regurgitation, cardiac surgery needs to be considered for management. A multidisciplinary team including cardiology, heart failure, critical care cardiology, cardio-oncology, oncology, cardiac surgery, and other specialties may be involved in the management of cardiac masses and their manifestations. References – A Mystery Mass in the Heart – Cardiac Lymphoma 1. Alerhand, S., & Carter, J. (2019). What echocardiographic findings suggest a pericardial effusion is causing tamponade? American Journal of Emergency Medicine, 37(2), 321-326. 2. McAllister, H. A., & Fenoglio, J. J. (1978). Tumors of the Cardiovascular System. Atlas of Tumor Pathology, Series 2. Armed Forces Institute of Pathology, Washington DC, 2, 20. 3. Tyebally, S., Chen, D., Bhattacharyya, S., Mughrabi, A., Hussain, Z., Manisty, C., Westwood, M., Ghosh, A. K., & Guha, A. (2020). Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC. CardioOncology, 2(2), 293-311. 4. Motwani, M., Kidambi, A., Herzog, B. A., Uddin, A., Greenwood, J. P., & Plein, S. (2013). MR imaging of cardiac tumors and masses: a review of methods and clinical applications. Radiology, 268(1), 26-43. 5. Spodick, D. H. (2003). Acute cardiac tamponade. New England Journal of Medicine, 349(7), 684-690.

In this episode, Dr. Gurleen Kaur (medicine resident at Brigham and Women’s Hospital and Director of CardioNerds Internship) and CardioNerds Academy interns Dr. Akiva Rosenzveig (medicine intern at Cleveland Clinic), Dr. Chelsea Tweneboah (medicine intern at Stonybrook University), student doctor Shivani Reddy (medical student at Western Michigan University), student doctor Diane Masket (medical student at Rowan School of Osteopathic Medicine), and student doctor Tina Reddy (medical student at Tulane University School of Medicine) discuss with Dr. Michelle Kittleson (Director of Education in Heart Failure and Transplantation, Director of HF Research, and Professor of Medicine at Cedars Sinai) about Mastering the Art of Patient Care. Dr. Kittleson shares pearls of wisdom from her book on topics including career transitions, mentorship, dealing with uncertainty, learning from mistakes, delivering difficult news, and being a woman and parent in medicine.   This episode was planned by Dr. Gurleen Kaur and episode audio was edited by student doctor Tina Reddy. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

Dr. Amit Goyal (CardioNerds co-founder), Dr. Jessie Holtzman (House Faculty in CardioNerds Academy and cardiology fellow at UCSF), and Dr. Megan McLaughlin (CardioNerds Scholar and cardiology fellow at UCSF) discuss stimulant-associated cardiomyopathy with Dr. Jonathan Davis (Associate Professor at UCSF the Director of the Heart Failure Program at Zuckerberg San Francisco General Hospital) and Dr. Soraya Azari (Associate Clinical professor at UCSF, with specialty in hospital medicine, primary care, HIV medicine, and addiction medicine).   Methamphetamine-associated heart failure admissions have steadily increased in the United States over the past decade. Substance use disorders more broadly are thought to complicate at least 15% of all heart failure hospitalizations and amphetamine use has been shown to be an independent predictor of heart failure readmission across the country. At safety net and public hospitals, these numbers may rise even higher. This episode reviews the pathophysiology of stimulant associated cardiomyopathy, highlights treatment options for stimulant use disorder, and discusses novel models of co-management of heart failure and substance use disorder.  Notes were drafted by Dr. Jessie Holtzman. Audio editing by CardioNerds academy intern, Pace Wetstein. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Heart Success Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls – Stimulant-Associated Cardiomyopathy Though there are no pathognomonic traits of stimulant-associated cardiomyopathy, common echocardiographic features include biventricular dilated cardiomyopathy and/or pulmonary hypertension with a dilated, hypokinetic right ventricle and underfilled left ventricle. Enjoy CardioNerds Episode 312. Case Report: Life in the Fast Lane Leads to a Cardiac Conundrum to learn from a case of stimulant associated pulmonary arterial hypertension.   Not all cardiomyopathy in patients who use stimulants is due to stimulant use. Do your due diligence. Patients who use stimulants should undergo a broad work-up to diagnose the etiology of cardiomyopathy.   Tips for taking a substance use history:  Ask permission to discuss the topic.  Normalize the behavior.  Use specific drug names (also, learn the local drug nicknames!).  Ask about any history of prior treatment and periods of abstinence.  Screen for risk of harm or overdose   Try using a phrase like “I’m asking you this because I want to know if the way you are using drugs can impact your health and keep you safe.”  There are no FDA-approved medications to treat stimulant use disorder. Common off-label therapies include mirtazapine and bupropion/naltrexone.   Contingency management programs work off the principle of operant conditioning; they reward patients for maintaining abstinence from substance use.   For clinicians to seek assistance in providing treatment for stimulant use disorder, important resources include:   SAMSA (national help line 1-800-662-HELP or online resource locator)  HarmReduction.Org  Never Use Alone hotline (800-484-3731)  Show notes – Stimulant-Associated Cardiomyopathy 1. What are common clinical presentations of stimulant-associated cardiomyopathy?   Stimulants have multifactorial physiologic impacts, due both to pharmacologic properties (adrenergic stimulation and vasoconstriction) and direct toxic effects. Clinical manifestations may include hypertension, tachyarrhythmias, acute myocardial infarction, cardiomyopathy, pulmonary hypertension, aortic dissection, and sudden cardiac death.   On echocardiogram, stimulant-associated cardiomyopathy may manifest as biventricular dilated cardiomyopathy, compensatory tachycardia, LV thrombus, and/or pulmonary hypertension (WHO Group I)  2. What is the pathophysiology of stimulant associated cardiomyopathy?   Though the exact mechanisms driving stimulant-associated cardiomyopathy are unknown, myocardial injury is thought to be related to excess catecholamines and the generation of reactive oxygen species, mitochondrial dysfunction, and the downstream effects of microvascular dysfunction and vasospasm.   Some authors have proposed a two-hit phenomenon whereby stimulant use and vulnerable genetics result in more severe clinical presentations.  3. What are common treatment options for stimulant-associated cardiomyopathy and stimulant use disorder in the presence of cardiovascular disease?   As with heart failure in general, start by ensuring that patients receive appropriate goal-directed medical therapy (GDMT) with an ACEI/ARB/ARNI, beta-blocker, MRA, and SGLTi.   If patients struggle with medication adherence, be sure to address the social determinants of health to allow for improved adherence. For instance, consider using bubble packs to help mitigate polypharmacy.   4. What is the Heart Plus Clinic and how can cardiologists work in an interdisciplinary fashion to address both cardiovascular disease and substance use disorders?  The Heart Plus clinic is a multidisciplinary team that links addiction medicine providers and the cardiovascular teams together. The clinic uses contingency management to incentivize abstinence from substance use and works to address barriers to getting medications, taking medications, and navigating polypharmacy. Results are promising so far, with a pilot study demonstrating less stimulant use, more GDMT use, less urgent care use, and more primary care use, along with greater engagement, continuity, and rapport.    5. How do you take a substance use history?    Ask permission: “Is it ok if I ask you about ***”   Normalize the behavior: “Substance use is common” or “I have a lot of patients struggling with ***”   Use specific names when obtaining a drug use history (not just alcohol, tobacco, “drugs”). Learn the names of drugs in your region.   Try using phrases like “I’m asking you this because I want to know if the way you are using drugs can impact your health and keep you safe.”    Ask about their history of past treatment and periods of abstinence.  Screen for patients at risk of harm and/or overdose due to patterns of use and be sure to prescribe naloxone.  6. What are some useful resources for treating patients with active substance use disorders?  Though there currently no FDA-approved medications to treat stimulant use disorder, common off-label therapies include mirtazapine and bupropion/naltrexone.  Contingency management programs work off the principle of operant conditioning and reward patients for maintaining abstinence from substance use. In contingency management programs, a behavior is chosen that you want to see more frequently, and a reward is given. The reward must be given close to the time of behavior and be of sufficient magnitude to demonstrate the desired effect.    There are many resources to help both clinicians and patients treat substance sue disorders. Resources include the SAMSA national help line (1-800-662-HELP) or online resource locator for clinicians. Patients may also access HarmReduction.Org and the NeverUseAlone hotline (800-484-3731) for harm reduction resources.  References – Stimulant-Associated Cardiomyopathy 1. DesJardin J, Leyde S, Davis J. Weathering the perfect storm: management of heart failure in patients with substance use disorders. Heart. 2021;107(16):1353-4. doi: 10.1136/heartjnl-2021-319103. 2. Kevil CG, Goeders NE, Woolard MD, Bhuiyan MS, Dominic P, Kolluru GK, et al. Methamphetamine Use and Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2019;39(9):1739-46. doi: 10.1161/ATVBAHA.119.312461. 3. Kolaitis NA, Saggar R, De Marco T. Methamphetamine-associated pulmonary arterial hypertension. Curr Opin Pulm Med. 2022;28(5):352-60. 4. Leyde S, Abbs E, Suen LW, Martin M, Mitchell A, Davis J, et al. A Mixed-methods Evaluation of an Addiction/Cardiology Pilot Clinic With Contingency Management for Patients With Stimulant-associated Cardiomyopathy. J Addict Med. 2023;17(3):312-8. doi: 10.1097/ADM.0000000000001110. 5. Manja V, Nrusimha A, Gao Y, Sheikh A, McGovern M, Heidenreich PA, et al. Methamphetamine-associated heart failure: a systematic review of observational studies. Heart. 2023;109(3):168-77. doi: 10.1136/heartjnl-2022-321610. 6. Reddy PKV, Ng TMH, Oh EE, Moady G, Elkayam U. Clinical Characteristics and Management of Methamphetamine-Associated Cardiomyopathy: State-of-the-Art Review. J Am Heart Assoc. 2020;9(11):e016704. doi: 10.1161/JAHA.120.016704. https://www.ahajournals.org/doi/epub/10.1161/JAHA.120.016704 

CardioNerds (Drs. Amit Goyal and Dan Ambinder) join Dr. Emily Lee (LAC+USC Internal medicine resident) and Dr. Charlie Lin (LAC+USC Cardiology fellow) as the discuss an important case of stimulant-related (methamphetamine) cardiovascular toxicity that manifested in right ventricular dysfunction due to severe pulmonary hypertension. Dr. Jonathan Davis (Director, Heart Failure Program at Zuckerberg San Francisco General Hospital and Trauma Center) provides the ECPR for this episide. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig. With the ongoing methamphetamine epidemic, the incidence of stimulant-related cardiovascular toxicity continues to grow. We discuss the following case: A 36-year-old man was hospitalized for evaluation of dyspnea and volume overload in the setting of previously untreated, provoked deep venous thrombosis. Transthoracic echocardiogram revealed severe right ventricular dysfunction as well as signs of pressure and volume overload. Computed tomography demonstrated a prominent main pulmonary artery and ruled out pulmonary embolism. Right heart catheterization confirmed the presence of pre-capillary pulmonary arterial hypertension without demonstrable vasoreactivity. He was prescribed sildenafil to begin management of methamphetamine-associated cardiomyopathy and right ventricular dysfunction manifesting as severe pre-capillary pulmonary hypertension. “To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” – Sir William Osler. CardioNerds thank the patients and their loved ones whose stories teach us the Art of Medicine and support our Mission to Democratize Cardiovascular Medicine. CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ). Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media – stimulant-related (methamphetamine) cardiovascular toxicity Pearls – stimulant-related (methamphetamine) cardiovascular toxicity 1. Methamphetamine, and stimulants in general, can have a multitude of effects on the cardiovascular and pulmonary systems. Effects of methamphetamine are thought to be due to catecholamine toxicity with direct effects on cardiac and vascular tissues. Acutely, methamphetamine can cause vascular constriction and vasospasm, while chronic exposure is associated with endothelial damage. Over time, methamphetamine can cause pulmonary hypertension, atherosclerosis, cardiac arrhythmias, and dilated cardiomyopathy. 2. Methamphetamines are the second most commonly misused substances worldwide after opiates. Patients with methamphetamine-associated pulmonary arterial hypertension (PAH) have more severe pulmonary vascular disease, more dilated and dysfunctional right ventricles, and worse prognoses when compared to patients with idiopathic PAH. Additionally, patients with methamphetamine-associated cardiomyopathy and PAH have significantly worse outcomes and prognoses when compared to those with structurally normal hearts without evidence of PAH. Management includes multidisciplinary support, complete cessation of methamphetamine use, and guideline-directed treatment of PAH. 3. The diagnosis of pulmonary hypertension (PH) begins with the history and physical, followed by confirmatory testing using echocardiography and invasive hemodynamics (right heart catheterization). Initial serological evaluation may include routine biochemical, hematologic, endocrine, hepatic, and infectious testing. Though PH is traditionally diagnosed and confirmed in a two-step, echocardiogram-followed-by-catheterization model, other diagnostics often include electrocardiography, blood gas analysis, spirometry, ventilation/perfusion assessment, CT scans, MRIs, and/or genetic testing to evaluate for the myriad of etiologies that may contribute to the development of PH. 4. PH is characterized by remodeling of the pulmonary vasculature and a progressive increase of pulmonary vascular load, often resulting in right ventricular hypertrophy, remodeling, and dysfunction. PH is defined hemodynamically by a mean pulmonary arterial pressure ≥ 20 mmHg at rest when measured by right heart catheterization (RHC). Pre-capillary pulmonary hypertension due to pulmonary vascular disease is further defined by an elevation in pulmonary vascular resistance (PVR) of at least 3 wood units (WU). 5. Medications used to treat pulmonary arterial hypertension fall into four general mechanistic classes: calcium channel blockers, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin receptor agonists. Show Notes – stimulant-related (methamphetamine) cardiovascular toxicity How is pulmonary hypertension diagnosed with right heart catheterization (RHC)? Pulmonary hypertension is defined by mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg at rest. Pulmonary hypertension has three hemodynamic phenotypes – pre-capillary PH, post-capillary PH, and combined pre-/post-capillary PH. Isolated pre-capillary PH is defined by pulmonary vascular resistance (PVR) ≥ 3 woods units and pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg. Isolated post-capillary PH is defined by PVR < 3 woods units and PAWP > 15 mmHg. PVR is calculated by dividing the mean trans-pulmonary gradient (= PAWP – mPAP) by the cardiac output. Characteristics Clinical groups Isolated pre-capillary PH mPAP >20 mmHgPAWP ≤ 15 mmHgPVR ≥ 3 WU WHO 1,3,4, and 5 Isolated post-capillary PH mPAP >20 mmHgPAWP > 15 mmHgPVR < 3 WU WHO 2 and 5 Combined pre- & post-capillary PH mPAP >20 mmHgPAWP > 15 mmHgPVR ≥ 3 WU WHO 2 and 5 Classification of PAH by WHO Groups: WHO Group 1Pulmonary Arterial Hypertension WHO Group 2Pulmonary hypertension due to left sided heart disease WHO Group 3Pulmonary hypertension due to lung disease or hypoxia WHO Group 4Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions WHO Group 5Pulmonary hypertension with multifactorial mechanisms Idiopathic Left ventricular systolic and/or diastolic dysfunction Chronic obstructive pulmonary disease Chronic thromboembolic pulmonary hypertension Hematological Disease (Sickle cell disease) Hereditary Left-sided valvular heart disease Interstitial lung disease Obstruction of the pulmonary circulation by tumor or inflammation Systemic disorders (Sarcoidosis, Langerhans cell granulomatosis) Drug and toxin induced Other mixed restrictive or obstructive lung disease Metabolic disorders (Gaucher’s disease) Associated with connective tissue disease Sleep-disordered breathing Associated with HIV infection Alveolar hypoventilation disorders Associated with portal hypertension Chronic exposure to high altitude Congenital heart disease Schistosomiasis What is vasoreactivity testing? Pulmonary vasoreactivity testing is used to identify patients who may respond favorably to calcium channel blocker (CCB) treatment. Typically, this includes patients with idiopathic pulmonary arterial hypertension, heritable pulmonary arterial hypertension, or substance-related pulmonary arterial hypertension. It is usually performed at the time of RHC. Inhaled nitric oxide (NO) at 10–20 parts per million (ppm) is the standard of care for vasoreactivity testing with alternatives including intravenous adenosine and epoprostenol. A significant response to vasodilator therapy is defined by a reduction of the mean PAP by at least 10 mmHg and concurrent decrement of the absolute value to less than 40 mmHg, without a decrease in cardiac output. Vasoreactive PH should be treated with CCB therapies such as nifedipine, diltiazem, and amlodipine. Vasoreactivity is relatively rare, occurring in 10% or fewer individuals with PH who undergo testing. PH without vasoreactivity of significant response to CCB therapy should be managed with alternative class of medications (see below). What is the medical treatment for PAH? Medication treatment of pulmonary arterial hypertension comes in 4 general categories with the general mechanism is listed: Calcium channel blockers (nifedipine, diltiazem and amlodipine used in high doses) – used in patients with positive vasoreactivity testing. Endothelin receptor antagonists (ambrisentan, bosentan, macitentan) – inhibit binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells, which is enriched in pulmonary vasculature, resulting in vasodilation and subsequent decrease in pulmonary arterial pressure. Phosphodiesterase 5 inhibitors and guanylate cyclase stimulators (sildenafil, tadalafil, riociguat) – ihibition of the cyclic guanosine monophosphate (cGMP) degrading enzyme phosphodiesterase type 5 results in vasodilation through the NO/cGMP pathway in the pulmonary vasculature, which contains substantial amounts of this enzyme. Prostacyclin analogues and prostacyclin receptor agonists (epoprostenol, iloprost, treprostinil, beraprost) – prostacyclin is produced predominantly by endothelial cells and induces potent vasodilation of all vascular beds and patients with PAH have been shown to have a reduction of prostacyclin synthase expression in the pulmonary arteries. References – Ben-Yehuda O, Siecke N. Crystal Methamphetamine: A Drug and Cardiovascular Epidemic. JACC Heart Fail. Mar 2018;6(3):219-221. doi:10.1016/j.jchf.2018.01.004 Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. Feb 2012;141(2):354-362. doi:10.1378/chest.11-0676 Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. Aug 2019;156(2):323-337. doi:10.1016/j.chest.2019.02.004 Chin KM, Channick RN, Rubin LJ. Is methamphetamine use associated with idiopathic pulmonary arterial hypertension? Chest. Dec 2006;130(6):1657-63. doi:10.1378/chest.130.6.1657 Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. Jan 1 2016;37(1):67-119. doi:10.1093/eurheartj/ehv317 Hassoun PM. Pulmonary Arterial Hypertension. N Engl J Med. Dec 16 2021;385(25):2361-2376. doi:10.1056/NEJMra2000348 Hoeper MM, Humbert M, Souza R, et al. A global view of pulmonary hypertension. Lancet Respir Med. Apr 2016;4(4):306-22. doi:10.1016/s2213-2600(15)00543-3 Kevil CG, Goeders NE, Woolard MD, et al. Methamphetamine Use and Cardiovascular Disease. Arterioscler Thromb Vasc Biol. Sep 2019;39(9):1739-1746. doi:10.1161/atvbaha.119.312461 Reddy PKV, Ng TMH, Oh EE, Moady G, Elkayam U. Clinical Characteristics and Management of Methamphetamine-Associated Cardiomyopathy: State-of-the-Art Review. J Am Heart Assoc. Jun 2 2020;9(11):e016704. doi:10.1161/jaha.120.016704 Zhao SX, Kwong C, Swaminathan A, Gohil A, Crawford MH. Clinical Characteristics and Outcome of Methamphetamine-Associated Pulmonary Arterial Hypertension and Dilated Cardiomyopathy. JACC Heart Fail. Mar 2018;6(3):209-218. doi:10.1016/j.jchf.2017.10.006

The following question refers to Section 5.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by MGH medicine resident Dr. Christian Faaborg-Andersen, answered first by Dr. Jessie Holtzman, and then by expert faculty Dr. Laurence Sperling. Dr. Laurence Sperling is the Katz Professor in Preventive Cardiology at the Emory University School of Medicine and Founder of Preventive Cardiology at the Emory Clinic. Dr. Sperling was a member of the writing group for the 2018 Cholesterol Guidelines, serves as Co-Chair for the ACC’s Cardiometabolic and Diabetes working group, and is Co-Chair of the WHF Roadmap for Cardiovascular Prevention in Diabetes. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #29 What percentage of the European population currently meets the recommended physical activity guidelines (150 minutes moderate-intensity activity weekly or 75 minutes vigorous-intensity activity weekly)? A <10% B 10-25% C 25-50% D 50-75% E >75% Answer #29 Explanation The correct answer is A: <10% of the European population currently meets the recommended physical activity guidelines. The American Heart Association, European Society of Cardiology, and World Health Organization all share the recommendation that adults should engage in 150 minutes per week of moderate-intensity physical activity or 75 minutes per week of vigorous-intensity activity. They recognize that additional health benefits may be garnered from incremental increases to 300 minutes per week of moderate intensity activity or 150 minutes per week of vigorous intensity activity, with a recommendation to include both aerobic and muscular strength training activities. According to the WHO, physical inactivity is the 4th leading cause of death in the world. The statistics regarding physical inactivity are staggering. Recent studies have shown that <10% of the European population meets the minimum recommended levels of physical activity. Similarly, ¼ adults and ¾ adolescents (aged 11-17) do not currently meet the global recommendations for physical activity. The World Health Organization has created a Global Action Plan on Physical Activity 2018-2030 with the goal to achieve a 15% relative reduction in the global prevalence of physical inactivity by 2030. Society level interventions to increase physical activity have been proposed including school-based activity programs, improved accessibility of exercise facilities across the socioeconomic spectrum, and governmental consideration of physical activity when designing cities (i.e. including pedestrian and cycling lanes). Other policy suggestions with varying levels of evidence include focused media campaigns, economic incentives, targeting labeling of physical activity opportunities, and work-place wellness programs. Main Takeaway Despite growing awareness of the health consequences of sedentary behavior, fewer than 10% of adults currently meet the minimum recommended quantity of physical activity. Public health leaders may continue to consider novel legislative initiatives to augment physical activity on a societal level with architectural design and financial incentives. Guideline Loc. Section 5.2 CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 9.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Cedars Sinai medicine resident, soon to be Vanderbilt Cardiology Fellow, and CardioNerds Academy Faculty Dr. Breanna Hansen, and then by expert faculty Dr. Anu Lala. Dr. Lala is an advanced heart failure and transplant cardiologist, associate professor of medicine and population health science and policy, Director of Heart Failure Research, and Program Director for the Advanced Heart Failure and Transplant fellowship training program at Mount Sinai. Dr. Lala is Deputy Editor for the Journal of Cardiac Failure. Dr. Lala has been a champion and role model for CardioNerds. She has been a PI mentor for the CardioNerds Clinical Trials Network and continues to serve in the program’s leadership. She is also a faculty mentor for this very 2022 heart failure decipher the guidelines series. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #23 Mrs. Hart is a 63-year-old woman with a history of non-ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 20-25%) presenting with 5 days of worsening dyspnea and orthopnea.   At home, she takes carvedilol 12.5mg BID, sacubitril-valsartan 24-46mg BID, empagliflozin 10mg daily, and furosemide 40mg daily.   On admission, her exam revealed a blood pressure of 111/79 mmHg, HR 80 bpm, and SpO2 94%. Her cardiovascular exam was significant for a regular rate and rhythm with an audible S3, JVD to 13 cm H2O, bilateral lower extremity pitting edema with warm extremities and 2+ pulses throughout.  What initial dose of diuretics would you give her? A Continue home Furosemide 40 mg PO B Start Metolazone 5 mg PO C Start Lasix 100 mg IV D Start Spironolactone Answer #23 Explanation The correct answer is C – start Furosemide 100 mg IV. This is the most appropriate choice because patients with HF admitted with evidence of significant fluid overload should be promptly treated with intravenous loop diuretics to improve symptoms and reduce morbidity (Class 1, LOE B-NR). Intravenous loop diuretic therapy provides the most rapid and effective treatment for signs and symptoms of congestion. Titration of diuretics has been described in multiple recent trials of patients hospitalized with HF, often initiated with at least 2 times the daily home diuretic dose (mg to mg) administered intravenously. Titration to achieve effective diuresis may require doubling of initial doses, adding a thiazide diuretic, or adding an MRA that has diuretic effects in addition to its cardiovascular benefits. Choice A is incorrect as continuing oral loop diuretics is not recommended for acute decongestion. Moreover, Ms. Hart has become congested despite her home, oral diuretic regimen. Choice B and D are incorrect as starting a thiazide diuretic or a mineralocorticoid receptor antagonist are not first-line therapy for acute HF. Rather, in patients hospitalized with HF when diuresis is inadequate to relieve symptoms and signs of congestion, it is reasonable to intensify the diuretic regimen using either: a. higher doses of intravenous loop diuretics; or b. addition of a second diuretic (Class 2a, LOE B-NR). After instituting intravenous loop diuretic therapy, escalating attempts to achieve net diuresis include serial doubling of intravenous loop diuretic doses, which can be done by bolus or infusion, and sequential nephron blockade with addition of a thiazide diuretic, as detailed specifically in the protocol for the diuretic arms of the CARRESS and ROSE trials. MRAs have mild diuretics properties and the addition of MRAs can help with diuresis in addition to significant cardiovascular benefits in patients with HF. For patients hospitalized with HF, therapy with diuretics and other guideline-directed medications should be titrated with a goal to resolve clinical evidence of congestion to reduce symptoms and rehospitalizations (Class 1, LOE B-NR). For patients requiring diuretic treatment during hospitalization for HF, the discharge regimen should include a plan for adjustment of diuretics to decrease rehospitalizations (Class 1, LOE B-NR). Main Takeaway Patients admitted with acute HF should be promptly treated with intravenous loop diuretics. If current level of diuresis becomes inadequate to relieve symptoms and signs of congestion, it is reasonable to intensify the diuretic regimen using either: higher doses of intravenous loop diuretics or addition of a second diuretic (e.g., thiazide or MRA). All patients should have their diuretic regimen updated on discharge. Guideline Loc. Section 9.3 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

Dr. Daniel Ambinder (CardioNerds Co-Founder), Dr. Kelly Arps (Series Co-Chair and EP fellow at Duke University), Dr. Stephanie Fuentes Rojas (FIT Lead and EP fellow at Houston Methodist), and Dr. Ingrid Hsiung (Cardiology Fellow at Baylor Scott & White Health) discuss situational assessment of stroke and bleeding risk with expert faculty Dr. Hafiza Khan (Electrophysiologist at Baylor Scott & White Health). In this episode, we discuss stroke and bleeding risk in specific situations such as prior to cardioversion, triggered episodes, and perioperatively. These are scenarios that are commonly encountered and pose specific challenges. Episode notes were drafted by Dr. Stephanie Fuentes. Audio editing by CardioNerds Academy Intern, Dr. Maryam Barkhordarian. This CardioNerds Atrial Fibrillation series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Kelly Arps and Dr. Colin Blumenthal. This series is supported by an educational grant from the Bristol Myers Squibb and Pfizer Alliance. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. We have collaborated with VCU Health to provide CME. Claim free CME here! Disclosures: Dr. Ellis discloses grant or research support from Boston Scientific, Abbott-St Jude, advisor for Atricure and Medtronic. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Atrial Fibrillation PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes – Atrial Fibrillation: Situational Assessment of Stroke and Bleeding Risk In patients with persistent atrial fibrillation with tachycardia induced cardiomyopathy, timely restoration of normal rhythm is important. In patients not on established oral anticoagulation one option is to wait 3 weeks on oral anticoagulation prior to considering cardioversion. Another option is to pursue TEE prior to cardioversion as TEE is currently the gold standard imaging modality to exclude a LAA thrombus. Following cardioversion (chemical or electrical), anticoagulation must not be interrupted for 4 weeks due to atrial stunning. This is especially true for patients who have been in atrial fibrillation for an extended period of time. Individualizing assessment of stroke and bleeding risk is imperative when determining perioperative anticoagulation (AC) management. ACC has a helpful app (ManageAnticoag App) to make this easier. When considering AC in triggered atrial fibrillation (e.g., pneumonia, sepsis), it is important to consider the substrate that made the patient susceptible to developing atrial fibrillation. AC is favored in patients with high CHA2DS2-VAsC score and many traditional risk factors for atrial fibrillation as they are at high risk for future development of atrial fibrillation. Atrial fibrillation is a marker of poor outcomes in patients who have undergone coronary artery bypass graft (CABG) surgery. It is unclear if patients should be started on long-term AC for new onset atrial fibrillation after CABG regardless of risk factors. This is currently being investigated in the PACES trial. Notes – Atrial Fibrillation: Situational Assessment of Stroke and Bleeding Risk How do we choose an imaging modality for excluding LAA thrombus exclusion prior to cardioversion? TEE is the gold standard. It also provides other information that is important for management of atrial fibrillation (e.g. LA size/volume, presence/degree of mitral regurgitation/stenosis, ejection fraction). Gated cardiac CTA may have a growing role for evaluation of LAA thrombus. What is the data behind the recommendation for uninterrupted AC following cardioversion and what is atrial stunning? All patients should be anticoagulated for four weeks after cardioversion, regardless of the mechanism of cardioversion or CHA2DS2-VAsC score. As discussed in prior episodes, those who meet long term criteria for AC should be anticoagulated indefinitely. The term “atrial stunning” refers to the electro-mechanical dissociation of the LAA following cardioversion. The longer one is in atrial fibrillation, the longer it takes for the LAA contraction/LAA flow velocities to recover after restoration of normal rhythm. During the period of atrial stunning, there is increased risk of LAA thrombus formation, hence AC should not be interrupted. The first 72 hours post cardioversion are the highest risk for LAA thrombus formation followed by the subsequent 4 weeks. What is the approach of perioperative AC management in patients with atrial fibrillation? ACC has a helpful app (ManageAnticoag App), to individualize the decision of when/how to stop and resume AC peri-procedurally. One needs to ascertain three factors: 1) surgical bleeding risk, 2) stroke risk, and 3) the patient’s individual bleeding risk (e.g., medications, supplements, renal function, etc.). The BRDIGE trial investigated the need to bridge patients on and off anticoagulation perioperatively. The trial was small and patient characteristics of the study (mostly male, low percentage of patients with high CHADS score) do not allow for generalizability of study findings to all patients. Many patients do not require perioperative bridging, but individual patient factors should be used to make this decision. High risk features that warrant heparin bridging include recent stroke, mechanical valve, or mitral stenosis. Should consider bridging in patients with high CHA2DS2-VAsC score as these patients only made up a small portion of the BRIDGE trial. What is the approach to AC in patients with triggered atrial fibrillation? Similar to a fire, atrial fibrillation requires a substrate (i.e., combustible material) and a trigger (i.e., a match) to initiate. Though you can treat and therefore remove the trigger (e.g., pneumonia), patients with a substrate conducive to atrial fibrillation remain at high risk of atrial fibrillation in the future. If they were to convert to atrial fibrillation without clear symptoms in the future, they would be at risk for stroke and might not be started on AC. As such, long-term AC should be evaluated in a similar manner to those with paroxysmal or persistent atrial fibrillation without a clear trigger. The patient population with true “triggered” atrial fibrillation may be limited to those with thyrotoxicosis as hyperthyroidism can trigger atrial fibrillation even in patients with structurally normal hearts and background risk for future atrial fibrillation.  Atrial fibrillation after cardiac surgery (e.g., CABG, mitral valve repair/replacement) should be managed with a coordinated heart team approach. Anticoagulation should likely be favored if bleeding risk is acceptable and patient has known risk factors, especially in valve surgeries where patients often have had longstanding LA pressure or volume overload. Atrial fibrillation following CABG has been associated with poor outcomes, though it is currently unclear if patients without traditional risk factors require long-term AC. This is currently being studied in the PACES trial. References January, C.T, Wann, L.S, Alpert, J.S., Calkins, H, Cigarroa, J.E., Cleveland, J.C., Conti, J.B., Ellinor P.T et al 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American college of Cardiology/American heart Asocciation Task Force on Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology, 6421, e1-76. Dagres N, Kornej J, Hindricks G, et al. Prevention of Thromboembolism After Cardioversion of Recent-Onset Atrial Fibrillation. J Am Coll Cardiol. 2013 Sep, 62 (13) 1193–1194.https://doi.org/10.1016/j.jacc.2013.06.019

The following question refers to Section 4.7 and Table 18 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Student Dr. Shivani Reddy, answered first by Fellow at Johns Hopkins Dr. Rick Ferraro, and then by expert faculty Dr. Roger Blumenthal. Dr. Roger Blumenthal is professor of medicine at Johns Hopkins where he is Director of the Ciccarone Center for the Prevention of Cardiovascular Disease. He was instrumental in developing the 2018 ACC/AHA CV Prevention Guidelines. Dr. Blumenthal has also been an incredible mentor to CardioNerds from our earliest days. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #28 Mr. A. C. is a 78-year-old gentleman with a long-standing history of HTN receiving antihypertensive medications & dietary management for blood pressure control. What is the target diastolic blood pressure recommendation for all treated patients such as Mr. A.C.? A < 80 mmHg B < 90 mmHg C < 70 mmHg D < 95 mmHg E < 100 mmHg Answer #28 Explanation The correct answer is A: DBP < 80 mmHg Blood pressure treatment targets: when drug treatment is used, the aim is to control BP to target within 3 months. Blood pressure treatment targets in the 2021 ESC Prevention guidelines are more aggressive than previously recommended, as evidence now suggests the previously recommended targets were too conservative, especially for older patients. The magnitude of BP lowering is the most important driver of benefit. ·       It is recommended that the first objective of treatment is to lower BP to <140/90 mmHg in all patients, and that subsequent BP targets are tailored to age and specific comorbidities (Class 1). ·       In treated patients aged 18-69 years, it is recommended that SBP should ultimately be lowered to a target range of 120 – 130 mmHg in most patients (Class 1). ·       In treated patients aged ≥70 years, it is recommended that SBP should generally be targeted to <140 and down to 130 mmHg if tolerated (Class 1). ·       In all treated patients, DBP is recommended to be lowered to <80 mmHg (Class I). This change in the BP target range for older people compared with the 2016 ESC prevention guidelines is supported by evidence that these treatment targets are safely achieved in many older patients and are associated with significant reductions in the risk of major stroke, HF, and CV death. It also takes into account that the even lower SBP in the intensively treated group in SPRINT (Systolic Blood Pressure Intervention Trial) (mean 124 mmHg) probably reflects a conventional office SBP range of 130-139 mmHg. It is recognized, however, that the evidence supporting more strict targets is less strong for very old people (>80 years) and those who are frail. Also, in these older and especially frail patients, it may be difficult to achieve the recommended target BP range due to poor tolerability or adverse effects, and high-quality measurement and monitoring for tolerability and adverse effects is especially important in these groups. Main Takeaway The first step in HTN management in all groups is a reduction to SBP < 140 mmHg and DBP < 80 mmHg, with further targets depending on age and comorbidities as specified by Table 18 of the 2021 ESC Prevention Guidelines. Guideline Loc. 1.     4.7.5.3 page 3285 2.     Table 18 page 3287 CardioNerds Decipher the Guidelines – 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The following question refers to Section 8.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Western Michigan University medical student & CardioNerds Intern Shivani Reddy, answered first by University of Southern California cardiology fellow and CardioNerds FIT Trialist Dr. Michael Francke, and then by expert faculty Dr. Prateeti Khazanie. Dr. Khazanie is an associate professor and advanced heart failure and transplant Cardiologist at the University of Colorado. Dr. Khazanie is an author on the 2022 ACC/AHA/HFSA HF Guidelines, the 2021 HFSA Universal Definition of Heart Failure, and multiple scientific statements. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Clinical Trials Talks Question #22 You are taking care of a 34-year-old man with chronic systolic heart failure from NICM with LVEF 20% s/p CRT-D. The patient was admitted 1 week prior with acute decompensated heart failure. Despite intravenous diuretics the patient developed acute kidney injury, and ultimately placed on intravenous inotropes on which he now seems dependent. He has been following up with an advanced heart failure specialist as an outpatient and has been undergoing evaluation for heart transplantation, which was subsequently completed in the hospital.   His exam is notable for an elevated JVP, a III/VI holosystolic murmur, and warm extremities with bilateral 1+ edema. His most recent TTE shows LVEF 20%, moderate MR, moderate-severe TR and estimated RVSP 34 mmHg. His most recent laboratory data shows Na 131 mmol/L, Cr 1.2 mg/dL, and lactate 1.6 mmol/L. Pulmonary artery catheter shows RA 7 mmHg, PA 36/15 mmHg, PCWP 12 mmHg, CI 2.4 L/min/m2 and SVR 1150 dynes*sec/cm5.   The patient was presented at transplant selection committee and approved for listing for orthotopic heart transplant. What is the most appropriate next step in the management of this patient? A Refer patient for transcatheter edge-to-edge repair for MR B Continue IV inotropes as a bridge-to-transplant C Refer patient for tricuspid valve replacement D Initiate 1.5L fluid restriction Answer #22 Explanation The correct answer is B – continue IV inotropes as a bridge-to-transplant. Positive inotropic agents may improve hemodynamic status, but have not been shown to improve survival in patients with HF. These agents may help HF patients who are refractory to other therapies and are suffering consequences from end-organ-hypoperfusion. Our patient is admitted with worsening advanced heart failure requiring intravenous inotropic support. He has been appropriately evaluated and approved for heart transplant. He has demonstrated the requirement of continuous inotropic support to maintain perfusion. In patients such as this with advanced (stage D) HF refractory to GDMT and device therapy who are eligible for and awaiting MCS or cardiac transplantation, continuous intravenous inotropic support is reasonable as “bridge therapy” (Class 2a, LOE B-NR). Continuous IV inotropes also have a Class 2b indication (LOE B-NR) in select patients with stage D HF despite optimal GDMT and device therapy who are ineligible for either MCS or cardiac transplantation, as palliative therapy for symptom control and improvement in functional status. Conversely, long-term use of either continuous or intermittent intravenous inotropic agents, for reasons other than palliative care or as a bridge to advanced therapies, is potentially harmful (Class 3: Harm, LOE B-R). As of yet there is lack of clear evidence suggesting the benefit of one inotrope over another. To minimize adverse effects, the lowest possible dose of inotropes should be used, although the potential for development of tachyphylaxis should be acknowledged and the choice/dose of agent may need to be changed over time for longer periods of use. In addition, the ongoing need for inotropic support and the possibility of discontinuation should be regularly assessed. Although guidelines give a Class 2a recommendation for transcatheter edge-to-edge MV repair in patients with reduced EF and severe MR with persistent symptoms despite GDMT, this patient’s MR was graded as moderate on his most recent TTE and as such, he would not be an appropriate candidate for TEER. Although guidelines give a Class 1 recommendation for multidisciplinary management of patients with HF and VHD, as well as referral for consideration of intervention in patients with refractory TR, there are currently no guideline recommendations supporting surgical TVR in advanced HF patients with TR. Although fluid restriction has been associated with modest improvements in hyponatremia in patients with advanced HF, the clinical benefits of this therapy remain uncertain and as such was given a Class 2b recommendation in the clinical guidelines.   Main Takeaway Continuous intravenous inotropic support can be considered in patients with advanced heart failure refractory to GDMT who are awaiting durable MCS or heart transplant as “bridge therapy” (Class 2a) or for palliative therapy in patients with advanced HF who are ineligible for MCS/transplant (Class 2b), but is potentially harmful for long-term use for reasons beyond palliation or bridge to advanced therapies (class 3 recommendation). Guideline Loc. Section 8.3 Table 20 Decipher the Guidelines: 2022 Heart Failure Guidelines PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

The CardioNerds and Pulm PEEPs have joined forces to co-produce this important episode, delving into the management of decompensated right ventricular failure in pulmonary arterial hypertension. Joining us for this informative discussion are Pulm PEEPs co-founders, Dr. David Furfaro and Dr. Kristina Montemayor, along with Dr. Leonid Mirson (Internal Medicine Resident at Johns Hopkins Osler Medical Residency and Associate Editor of Pulm PEEPs), Dr. Bavya Varma (Internal Medicine Resident at Johns Hopkins, rising Cardiology Fellow at NYU, and CardioNerds Academy graduate), Dr. Mardi Gomberg-Maitland (Medical Director of the Pulmonary Hypertension Program at George Washington Hospital), and Dr. Rachel Damico (Pulmonologist and Associate Professor of Medicine at Johns Hopkins Hospital). Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. CardioNerds Heart Success Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show notes – Decompensated Right Ventricular Failure in Pulmonary Arterial Hypertension A 21-year-old woman with a past medical history notable for congenital heart disease (primum ASD and sinus venosus with multiple surgeries) complicated by severe PAH on home oxygen, sildenafil, ambrisentan, and subcutaneous treprostinil is presenting with palpitations, chest pain, and syncope. She presented as a transfer from an outside ED where she arrived in an unknown tachyarrhythmia and had undergone DCCV due to tachycardia into the 200s and hypotension. On arrival at our hospital, she denied SOB but did endorse nausea, leg swelling, and poor medication adherence. Her initial vitals were notable for a BP of 80/50, HR 110, RR 25, and saturating 91% on 5L O2.  On exam, she was uncomfortable appearing but mentating well. She had cool extremities with 1-2+ LE edema. Her JVP was 15cm H2O. She has an RV Heave and 2/6 systolic murmur. Her lungs were clear bilaterally. Her labs were notable for Cr 2.0, an anion gap metabolic acidosis (HCO3 = 11), elevated lactate (4.1), elevated troponin to 14,  and a pro-BNP of ~5000.  Her CBC was unremarkable. Her EKG demonstrated 2:1 atrial flutter at a rate of 130. Diagnosing RV failure in patients with PH: RV dysfunction and RV failure are two separate entities. RV dysfunction can be measured on echocardiography, but RV failure can be thought of as a clinical syndrome where there is evidence of RV dysfunction and elevated right sided filling pressures. RV failure is a spectrum and can present with a range of manifestations from evidence of R sided volume overload and markers of organ dysfunction, all the way to frank cardiogenic shock. Most patients with RV failure are not in overt shock. One of the first signs of impending shock in patients with RV failure is the development of new or worsening hypoxemia. Patients with decompensated RV failure approaching shock often do not present with symptoms classic for LV low flow state. Instead, hypoxia 2/2 VQ mismatching may be the first sign and they can be otherwise well appearing. Particularly because patients with PH tend to be younger, they can often appear compensated until they rapidly decompensate. Causes of decompensation for patients with RV dysfunction and PH: Iatrogenesis (inadvertent cessation of pulmonary vasodilators by providers, surgery if providers are not familiar with risks of anesthesia), non-adherence to pulmonary vasodilators (either due to affordability issues or other reasons), infections, arrhythmias (particularly atrial arrhythmias), and progression of underlying disease. Patients with atrial arrhythmias (atrial flutter or atrial fibrillation) and pulmonary hypertension do not tolerate the loss of the atrial kick well as it contributes a significant amount to their RV filling and impacts their cardiac output. It is often difficult to determine if the atrial arrhythmia is a cause or effect of decompensated RV failure, but its presence is associated with a worse prognosis. Efforts should be made to re-establish normal sinus rhythm in patients with decompensated RV failure and atrial arrhythmias.  A patient’s home PH medications should never be stopped for any reason upon admission unless on the basis of recommendations by a pulmonary hypertension provider as this is often a cause of decompensation inpatient Interpreting findings on echocardiogram:  Echo is a useful screening tool. When interpreting evidence of RV dysfunction, it is important to look at the global picture and not just one measurement. RVSP, though commonly reported, may be of limited value when evaluating for decompensation. It’s a function of blood pressure, heart rate, and cardiac output. RVSP may even decline as shock worsens. TAPSE is useful as a marker of RV dysfunction if it is reduced, but it is difficult to follow over time and only gives information about cardiac function around the annulus; it may be normal even when apical RV function is depressed. RV fractional area of change may be more useful for global RV function. It is important to pay attention to the RV size overall, the degree of TR, and the presence of effusion all of which are associated with RV dysfunction. ­Tips regarding the interpretation of invasive hemodynamics: Cardiac output by thermodilution is the standard way to calculate PVR. Despite the degree of TR that is typically present, it is thought to be a better representation of cardiac output than the estimated Fick calculation.   Our experts agree that routine monitoring of invasive hemodynamics for acute decompensated RV failure is likely not helpful and has significant risks. A good external volume exam or CVP off a central venous catheter + central venous saturation will likely be all you need to navigate a patient with shock secondary to RV failure. A right heart catheterization (should be only done under fluoroscopy for patients with large RVs) may be helpful if the etiology of shock is unclear.  Management of decompensated RV failure in patients with pulmonary hypertension Managing preload is of utmost importance, perhaps the most important tenant of management of decompensated RV failure.  The overwhelming majority of patients with PH and decompensation are volume overloaded, it is exceptionally rare that someone would be dry. Furthermore, the myth that the RV is “preload responsive” is only true in the setting of acute RV injury (eg. RV infarction) and not so in patients with acute on chronic RV dysfunction. It is important to optimize preload in someone in decompensated RV failure and it is safe to do this more rapidly than traditionally taught. Exact goals varied between our experts, but anywhere from 2-4L net negative per day is reasonable especially if the patient is hemodynamically tolerating the fluid removal. If the patient is not responding to diuretics, hemodialysis with ultrafiltration may be necessary to optimize the patient. Afterload is the next tenant of management. Optimizing the following parameters will reduce the patient’s pulmonary vascular resistance and reduce afterload to the right ventricle. — Avoiding hypoxic pulmonary vasoconstriction, liberalize the patient’s O2 goal  — Avoid permissive hypercapnia and academia in this patient population — Do not withhold a patient’s pulmonary vasodilator until discussion with the PH team. If stopped inadvertently, restart this medication immediately. For patients with malfunctioning pumps, there is a phone number on the back that you can call for rapid troubleshooting. Sildanefil can be given IV if a patient is NPO.  — Inhaled nitric oxide can improve oxygenation and reduce afterload   — Intubation and mechanical ventilation greatly increase PVR and are poorly tolerated. Exacting care must be taken to titrate PEEP and tidal volume, and avoid intubation when possible. — Starting a new systemic pulmonary vasodilator in decompensated RV failure may be considered under close guidance from the pulmonary hypertension team Management of atrial arrhythmias: As above, patients with severe pulmonary hypertension do not tolerate loss of sinus rhythm well. If they are decompensated, every effort should be made to re-establish normal sinus rhythm.  Management of RV perfusion: Unlike the LV, the RV is perfused during BOTH systole and diastole. Maintaining effective coronary perfusion to the RV is essential in RV failure. For this reason, the systemic systolic pressure (as well as the mean arterial pressure) should be kept high enough to ensure that the RV is able to perfuse. There is no great body of evidence as to which pressor works best. Norepinephrine, vasopressin, and even phenylephrine are all reasonable choices to maintain appropriate perfusing blood pressure.  Inotropy: Patients in shock and RV failure do not always require inotropes, but if they do it’s often a sign of a grim prognosis. Either dobutamine or milrinone is reasonable, but the negative effects of these drugs (arrhythmias, tachycardia, and systemic hypotension) may limit their uses.  Mechanical circulatory support: Limited options are available. Balloon pumps and Impella devices have limited roles except in expert centers, and ECMO remains the standard of care. ECMO (either V-V or V-A) may have utility as a bridge to recovery if a reversible cause is identified, or a bridge to transplant if the patient is on the transplant list.  Goals of care: The prognosis of a patient admitted to the ICU with acute on chronic decompensated RV failure is guarded, with very high mortality rates even if not in shock It is important for the patient’s longitudinal pulmonary hypertension provider to discuss the prognosis and goals of care ahead of time but this is not always possible. If they are admitted, early discussions regarding code status and prognosis are essential. It may be helpful to bring in the patient’s longitudinal pulmonary hypertension doctor into these discussions if possible.  References – Decompensated Right Ventricular Failure in Pulmonary Arterial Hypertension Ventetuolo CE, Klinger JR. Management of acute right ventricular failure in the intensive care unit. Ann Am Thorac Soc. 2014 Jun;11(5):811-22. doi: 10.1513/AnnalsATS.201312-446FR. PMID: 24828526; PMCID: PMC4225807. Arrigo M, Huber LC, Winnik S, Mikulicic F, Guidetti F, Frank M, Flammer AJ, Ruschitzka F. Right Ventricular Failure: Pathophysiology, Diagnosis and Treatment. Card Fail Rev. 2019 Nov 4;5(3):140-146. doi: 10.15420/cfr.2019.15.2. PMID: 31768270; PMCID: PMC6848943. Kholdani CA, Fares WH. Management of Right Heart Failure in the Intensive Care Unit. Clin Chest Med. 2015 Sep;36(3):511-20. doi: 10.1016/j.ccm.2015.05.015. Epub 2015 Jun 27. PMID: 26304287. Houston BA, Brittain EL, Tedford RJ. Right Ventricular Failure. N Engl J Med. 2023 Mar 23;388(12):1111-1125. doi: 10.1056/NEJMra2207410. PMID: 36947468.