CardioNerds cofounders Dr. Amit Goyal and Dr. Daniel Ambinder join Dr. Isabel Balachandran, Dr. Diego Celli from the Texas Heart Institute. They discuss the nuances of risk stratification management of intermediate risk pulmonary embolism. The ECPR for this episode was provided by Dr. Alam Mahboob (Associate Professor of Medicine at Baylor College of Medicine and the Department of Medicine and Associate Program Director for the Cardiovascular Disease Fellowship Program at Baylor). Audio editing by CardioNerds Academy Intern, Dr. Chelsea Amo Tweneboah.

“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.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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How do you define “submassive” pulmonary embolism?

How do you risk-stratify intermediate-risk pulmonary emboli?

What is the general approach to therapeutic interventions and treatment for submassive PE?

When do you consider systemic thrombolysis or catheter directed therapies for patients with intermediate-risk PE?

What are common complications after submassive pulmonary emboli?

What is a PERT team and what is their role in the management of pulmonary emboli?

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.

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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.

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.

Classification of PAH by WHO Groups:

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).

Medication treatment of pulmonary arterial hypertension comes in 4 general categories with the general mechanism is listed:

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.

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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. 

CardioNerds join Dr. Samid Muhammad Farooqui, Dr. Hiba Hammad, and Dr. Syed Talal Hussain, from the University of Oklahoma Pulmonary and Critical Care Medicine Fellowship Program, in Oklahoma City. The fellows will take us in a fascinating discussion of a case of rapidly progressing dyspnea and pulmonary hypertension in a patient with metastatic breast cancer. They will then reveal an interesting etiology of pulmonary hypertension, where the secret was on the wedge! University of Oklahoma faculty and expert in pulmonary hypertension and right ventricular physiology, Dr. Roberto J. Bernardo provides the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Dr. Christian Faaborg-Andersen.

A septuagenarian female, with a past medical history of metastatic breast adenocarcinoma, presented to the hospital with worsening dyspnea over a period of 3 weeks. She was found to be in rapidly progressive hypoxic respiratory failure with unremarkable chest x-ray, CTA chest, and V/Q scan. Transthoracic echocardiogram revealed elevated RVSP and a subsequent right heart catheterization showed pre-capillary pulmonary hypertension with a low cardiac index. She was treated for rapidly progressive RV dysfunction with inotropic support and inhaled pulmonary vasodilators until she decided to pursue comfort measures. Wedge cytology came back positive for malignant cells, confirming a diagnosis of Pulmonary Tumoral Thrombotic Microangiopathy (PTTM).

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).

“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.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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1. How do you approach dyspnea?

2. What are the different Pulmonary Hypertension groups?

Pulmonary Hypertension (PH) is divided into 5 main groups in the WHO classification, as follows:

3. How do you approach a patient with Pulmonary Hypertension?

4. What are the considerations for Pulmonary Hypertension etiologies in patient with malignancy? How is Pulmonary Tumoral Thrombotic Microangiopathy diagnosed?

5. What is the prognosis of PTTM and how is it treated?

Join CardioNerds to learn about patent ducts arteriosus and Eisenmenger syndrome! Dr. Dan Ambinder (CardioNerds co-founder), ACHD series co-chair Dr. Dan Clark,  Dr. Tony Pastor (ACHD fellow, Harvard Medical School), and Dr. Kate Wilcox, Medicine/Pediatrics Resident, Medical College of Wisconsin join Dr. Candice Silversides (Editor-in-chief #JACCAdvances) for this terrific discussion. Notes were drafted by Dr. Kate Wilcox. .Audio editing by CardioNerds Academy Intern, Dr. Maryam Barkhordarian.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark.

The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more

Disclosures: None

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Adult Congenital Heart Association
Founded in 1998, the Adult Congenital Heart Association is an organization begun by and dedicated to supporting individuals and families living with congenital heart disease and advancing the care and treatment available to our community. Our mission is to empower the congenital heart disease community by advancing access to resources and specialized care that improve patient-centered outcomes. Visit their website (https://www.achaheart.org/) for information on their patient advocacy efforts, educational material, and membership for patients and providers

CHiP Network

The CHiP network is a non-profit organization aiming to connect congenital heart professionals around the world. Visit their website (thechipnetwork.org) and become a member to access free high-quality educational material, upcoming news and events, and the fantastic monthly Journal Watch, keeping you up to date with congenital scientific releases. Visit their website (https://thechipnetwork.org/) for more information.

Heart University
Heart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of educational material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practicing provider. The site provides free content to a global audience in two broad domains: 1. A comprehensive curriculum of training modules and associated testing for trainees. 2. A curated library of conference and grand rounds recordings for continuing medical education. Learn more at www.heartuniversity.org/

CardioNerds (Amit and Dan) join join Dr. Andrew Dicks (Vascular medicine physician at Prisma Health, former fellow at Mass General Vascular) and Dr. Prateek Sharma (Vascular interventional & medicine fellow at MGH) for an ice-cold drinks at the Esplanade in Boston, MA to discuss a case about a patient who developed a pulmonary embolism and masterfully discuss the diagnosis and management of of pulmonary emboli. Dr. Ido Weinberg (Director, Vascular Medicine Fellowship at MGH) provides the ECPR for this episode.

Case Abstract: A 59-year-old Spanish-speaking man with no significant past medical history presents after falling 15-20 feet from a ladder and landing on his back. He was found to have an L1 fracture and left radial fracture and underwent T12-L2 fusion with neurosurgery on hospital day 1 and ORIF of left radial fracture with orthopedic surgery on hospital day 2. On hospital day 5, he develops acute onset tachycardia with HR in the 130s bpm with new O2 requirement associated with mild shortness of breath at rest without any chest discomfort. His labs were notable for an elevated troponin and proBNP. He underwent CTPA which demonstrated acute bilateral occlusive pulmonary emboli (PE) extending in the right and left main pulmonary arteries. TTE demonstrated right ventricle dilation. The patient was started on a heparin infusion and a PE response team (PERT) meeting was held to discuss treatment options. Given recent surgery, use of thrombolytic therapy was felt to be too risky and thus he was taken for percutaneous thrombectomy in the cath lab. PA pressure prior to intervention was 51/21 mmHg. The patient underwent suction thromboembelectomy with the Flow Triever device with extraction of thrombus and improvement in PA pressure to 19/11 mmHg. He was treated with anticoagulation thereafter and discharged home two days after the procedure.

Jump to: Case media – Case teaching – References

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1. While there are markers to suggest PE, such as ECG findings or evidence of RV dilatation, a PE cannot be confirmed without imaging.
2. Elevation of cardiac biomarkers and evidence of RV dysfunction are used to risk stratify PE, not the degree of thrombus burden or locale of thrombus.
3. Enoxaparin is the preferred anticoagulant to initiate at time of PE diagnosis if comorbidities allow.
4. Optimal treatment of intermediate risk PE remains uncertain as there is little data about long-term outcomes. Aggressive treatment should be used judiciously and chosen on a case-by-case basis.
5. PE response teams (PERT) allow for multidisciplinary expert opinion in the face of scarce evidence to determine what is felt to be the best management strategy.

1. What is a PERT team and why is it helpful?

• We have several tools and approaches for the management of PE. There are also many subspecialities involved in the care of patients with PE, including vascular medicine, intervention cardiology, hematology, pulmonology, cardiac surgery, radiology, emergency department, intensive care, and more. As such, the best treatment plan for a given patient with PE can be challenging, especially if the services involved in treatment of the PE function in silos.
• PERT, or PE Response Team, was built to address this concern. It is a multidisciplinary team that originated at MGH whose goal is to coordinate care for high-risk PE patients and advance PE-related care in the institution.
• PERT allows for multidisciplinary expert opinion in the face of scarce evidence to determine what is felt to be the best management strategy.

2. How do we risk stratify patients with PE?

• Risk stratification is largely dependent on the hemodynamic significance caused by the PE. In addition to vital sign derangement, patients with PE should also be evaluated for evidence of cardiac strain due to PE by checking for evidence of RV dilatation on CT or TTE and for elevation of cardiac biomarkers. The combination of this information is used to risk stratify patients. Additionally, risk stratification tools, such as the PESI and sPESI scores, are used to guide risk stratification.
• Based on the ESC 2019 guidelines, PEs are stratified into high risk, intermediate-high risk, intermediate-low risk, or low risk.
  • High risk: evidence of hemodynamic instability as defined by hypotension or shock.
  • Intermediate-high risk: evidence of both RV dysfunction on imaging AND elevated cardiac biomarkers in the absence of HD instability
  • Intermediate-low risk: evidence of either RV dysfunction on imaging OR elevated cardiac biomarkers in the absence of HD instability
  • Low risk: no evidence of cardiac dysfunction on imaging or labs and no evidence of HD instability.
• Risk stratification is important as it helps guide medical management of patients. Important factors that have not been associated with PE severity include degree of thrombus burden and location of clot.

3. What do we know about optimal management of patients with intermediate risk PE?

• Unfortunately, data is fairly limited with regards to the optimal management strategy for patients with intermediate risk PE, namely whether anticoagulation alone is sufficient versus if a patient would benefit from more advanced therapies. All patients should be started on anticoagulation, preferably SQ enoxaparin if comorbidities allow, as soon as possible (if there are no contraindications to anticoagulation). However, choosing which patients would benefit from more advanced therapies remains limited.
• Thrombolysis has been associated with lower all-cause mortality in patients with intermediate-risk PE when compared to anticoagulation alone. However, not surprisingly, thrombolysis was also associated with more major bleeding, including intracranial hemorrhage. In the ULTIMA trial, catheter directed thrombolysis was shown to improve RV dysfunction more quickly compared to anticoagulation at 24 hours. However, at 90 days, there was no difference in degree of RV dysfunction between the two groups.
• Percutaneous thrombectomy devices have been shown to be safe and effective at reducing RV size. However, there are no head-to-head comparisons of these modalities versus anticoagulation or thrombolysis and data is limited regarding the long-term efficacy.
• Choosing the correct patient to proceed with advanced therapies remains challenging and the decision is often made on a case-by-case basis. There are ongoing randomized control trials that will hopefully assist in guiding this decision making.

4. What about management for those with high-risk PE?

• High risk PEs mandate aggressive and rapid treatment.
• Thrombolysis has been shown to have a mortality benefit compared to anticoagulation. 
• Catheter directed thrombolysis can be considered in high-risk PE; however, rapid implementation needs to be available.
• VA-ECMO has also been demonstrated to reduce mortality in these patients.

5. What additional treatment options are available for patients with PE who are not improving on anticoagulation and have a contraindication to thrombolytic therapy?

• There are several contraindications to thrombolytic therapy, including recent surgery, CVA, or bleeding. Percutaneous and surgical thrombectomy should be considered in these patients.
• Surgical thrombectomy is effective but does require significant anticoagulation during the surgery while the patient is on cardiac bypass. For this reason, patients that have a contraindication to thrombolysis might not be able to tolerate the high levels of anticoagulation required for the surgery and thus a surgical thrombectomy might not be a feasible option.
• There are several percutaneous thrombectomy devices on the market currently which have been shown to be safe and effective at reducing the RV size in the acute period. Because these devices do not require thrombolytic agents, the risk of bleeding is lower and there is less ICU utilization. However, there have not been head-to-head comparisons between these devices and other treatment modalities.

1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405
2. Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2017;2:CD001100. doi:10.1002/14651858.CD001100.pub4
3. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411. doi:10.1056/NEJMoa1302097
4. Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421. doi:10.1001/jama.2014.5990
5. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479-486. doi:10.1161/CIRCULATIONAHA.113.005544
6. Subramaniam RM, Mandrekar J, Chang C, et al. Pulmonary embolism outcome: a prospective evaluation of CT pulmonary angiographic clot burden score and ECG score. AJR Am J Roentgenol. 2008;190(6):1599-1604. doi:10.2214/AJR.07.2858
7. Jain CC, Chang Y, Kabrhel C, et al. Impact of Pulmonary Arterial Clot Location on Pulmonary Embolism Treatment and Outcomes (90 Days). Am J Cardiol. 2017;119(5):802-807. doi:10.1016/j.amjcard.2016.11.018
8. Tu T, Toma C, Tapson VF, et al. A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study. JACC Cardiovasc Interv. 2019;12(9):859-869. doi:10.1016/j.jcin.2018.12.022

It’s another session of CardioNerds Rounds! In these rounds, Co-Chair, Dr. Karan Desai (previous FIT at the University of Maryland Medical Center, and now faculty at Johns Hopkins) joins Dr. Ryan Tedford (Professor of Medicine and Chief of Heart Failure and Medical Directory of Cardiac Transplantation at the Medical University of South Carolina in Charleston, SC) to discuss the nuances of managing pulmonary hypertension in the setting of left-sided heart disease. Dr. Tedford is an internationally-recognized clinical researcher, educator, clinician and mentor, with research focuses that include the hemodynamic assessment of the right ventricle and its interaction with the pulmonary circulation and left heart.

This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes. 

Speaker disclosures: None

Cases discussed and Show Notes • References • Production Team

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Case #1 Synopsis:

A woman in her late 30s presented to the hospital with 4 weeks of worsening dyspnea. Her history includes dilated non-ischemic cardiomyopathy diagnosed in the setting of a VT arrest around 10 years prior. Over the past 10 years she has been on guideline-directed medical therapy with symptoms that had been relatively controlled (characterized as NYHA Class II), but without objective improvement in her LV dimensions or ejection fraction (LVEF 15-20% by TTE and CMR and LVIDd at 6.8 cm). Over the past few months she had been noting decreased exercise tolerance, worsening orthopnea, and episodes of symptomatic hypotension at home. When she arrived to the hospital, she presented with BP 95/70 mmHg, increased respiratory effort, congestion and an overall profile consistent with SCAI Stage C-HF shock. In the case, we go through the hemodynamics at various points during her hospitalization and discuss options for management including medical therapy and mechanical support. The patient was eventually bridged to transplant with an Impella 5.5.

Initial Hemodynamics

Right Atrium (RA) Pressure Tracing:

Right Ventricle (RV) Pressure Tracing:

Pulmonary Artery (PA) Pressure Tracing:

Pulmonary Capillary Wedge Pressure (PCWP) Tracing:

Case 1 Rounding Pearls

1. One of the first points that Dr. Tedford made was thinking about our classic frameworks of characterizing acute decompensated heart failure, specifically the “Stevenson” classification developed by Dr. Lynne Stevenson that phenotypes patients along two axes: congestion (wet or dry) and perfusion (warm or cold). Dr. Tedford cautioned that young patients may not fit into these classic boxes well, and that a normal lactate should not re-assure the clinician that perfusion is normal.
2. In reviewing the waveforms, Dr. Tedford took a moment to note that besides just recording the absolute values of the pressures transduced in each chamber or vessel, it is critical to understand the morphology of the tracings themselves. For instance, with the RA pressure tracing above, there is no respiratory variation in the mean pressure. This is essentially a “resting Kussmaul’s sign,” which is typically indicative of significant RV dysfunction. Thus, even though our echocardiogram in this case did not necessarily show a significantly dilated RV with mildly reduced longitudinal function (TAPSE), hemodynamically the patient is demonstrating significant RV compromise.
3. If we compare the RA pressure tracing to the PCWP, we see that there is respiratory variation in the PCWP tracing. We typically think of pronounced respiratory variation in the RA or PCWP tracing in the setting of obesity or lung disease, but loading conditions can also lead to significant respiratory variation.
4. As was noted during the case discussion, irreversible pulmonary hypertension is considered an absolute contraindication to heart transplantation though there is variation on the absolute threshold above which transplantation is contraindicated. Generally, a pulmonary vascular resistance (PVR) of 3 Woods Units is considered a contraindication to isolated cardiac transplantation. Testing for reversibility of an elevated PVR with a vasodilator like nitroprusside is common in this patient population.
5. In a study by Dr. Steven Hsu and colleagues, Pulmonary Artery Pulsatility Index (PAPi) was shown to be the hemodynamic factor that best correlated with intrinsic RV myocyte dysfunction in patients with advanced heart failure (using a cutoff of PAPi of 1.85). Dr. Tedford made note to remember that PAPi is highly influenced by RA pressure (the denominator in the ratio).

Case #2 Synopsis:

A woman in her late 40s presented to clinic for another opinion regarding her PH management. In regards to her history, in the 1990s she underwent a mechanical mitral valve replacement (MVR) for mixed mitral valve disease in the setting of rheumatic fever as well as a single vessel CABG (SVG to the RCA). In the early 2000s, she had developed severe and symptomatic tricuspid regurgitation (TR) and underwent redo sternotomy for TV repair (TVr). She had generally done well until the past year when she started developing dyspnea on light exertion, abdominal fullness, lower extremity edema and over the course of a year she had four hospitalizations for heart failure. Over her hospitalizations, she was also diagnosed with hemolytic anemia. Diagnostic work-up revealed pre and post-capillary PH. Dr. Tedford reviews the subsequent hemodynamic evaluation and provides insight on managing PH post valvular intervention. She was ultimately diagnosed with mitral paravalvular regurgitation treated with transcatheter PVL closure.

Initial Hemodynamics

RA Pressure Tracing

RV Pressure Tracing

PA Pressure Tracing

PCW Pressure Tracing

Left Ventricular (LV) Pressure Tracing

PCW and LV Simultaneous Pressure Tracing

Case 2 Rounding Pearls:

1. The patient had been placed on sildenafil for persistent PH post-valve intervention. Dr. Tedford briefly mentioned the SIOVAC trial which was designed to evaluate treatment with sildenafil (40 mg TID) compared with placebo amongst patients with persistent PH (mean PA pressure ≥ 30 mmHg) 1 year after valvular replacement or repair (majority of whom were patients that had mitral valve intervention). In this study, sildenafil was associated with worse functional status, specifically heart failure or dyspnea compared to placebo (34% vs. 20%, p = 0.04).
2. Dr. Tedford briefly touched upon the prognostic value of the diastolic pulmonary gradient (DPG, calculated as diastolic PA pressure subtracted by PCWP) in patients being considered for cardiac transplantation. We commonly use PVR and transpulmonary gradient (TPG) to characterize the degree of pre-capillary PH and suitability for transplantation. However, these markers are not ideal surrogates for pulmonary vascular remodeling and differentiating between fixed remodeling versus reversible changes. For instance, the TPG can be elevated not only as a result of pulmonary vascular remodeling but elevated LA pressures passively transmitted back to the pulmonary vasculature leading to elevations in the diastolic PA pressure.
3. The DPG was thought to potentially define higher risk left heart failure patients with clinically significant pre-capillary PH. However, in Dr. Tedford’s 2014 analysis, the DPG did not delineate higher risk among patients with elevated TPG and PVR undergoing cardiac transplantation. There could be several explanations including that the cutoff for abnormal DPG is low (≥7) and thus small errors in measurement could have significant influence on what is characterized as abnormal. Furthermore, the diastolic PA pressure measurement is particularly prone to ringing artifact.

1. Aslam MI, Jani V, Lin BL, et al. Pulmonary artery pulsatility index predicts right ventricular myofilament dysfunction in advanced human heart failure. Eur J Heart Fail. 2021 Feb;23(2):339-341. doi: 10.1002/ejhf.2084. Epub 2021 Jan 5. PMID: 33347674; PMCID: PMC8574988.
2. Bermejo J, Yotti R, García-Orta R, et al., on behalf of the Sildenafil for Improving Outcomes after VAlvular Correction (SIOVAC) investigators. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial.
3. Mehra MR, Canter CE, Hannan MM, et al; International Society for Heart Lung Transplantation (ISHLT) Infectious Diseases, Pediatric and Heart Failure and Transplantation Councils. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. J Heart Lung Transplant. 2016 Jan;35(1):1-23. doi: 10.1016/j.healun.2015.10.023. PMID: 26776864.
4. Tedford RJ, Beaty CA, Mathai SC et al. Prognostic value of the pre-transplant diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension. J Heart Lung Transplant. 2014 Mar;33(3):289-97. doi: 10.1016/j.healun.2013.11.008. Epub 2013 Nov 28. Erratum in: J Heart Lung Transplant. 2019 Feb;38(2):233. PMID: 24462554; PMCID: PMC3955214.
5. Thibodeau JT, Drazner MH. “The Role of the Clinical Examination in Patients With Heart Failure.” JACC Heart Failure (2018): 543-551.

CardioNerds (Amit Goyal and Daniel Ambinder), Cardio-OB series co-chair and University of Texas Southwestern Cardiology Fellow, Dr. Sonia Shah, episode lead fellow, Dr. Kaitlyn Ibrahim (Temple University now practicing with Lankenau Heart Group), join Dr. Afshan Hameed (Maternal-Fetal Medicine, Obstetrics & Gynecology, UC Irvine), Dr. Paul Forfia (Co-Director, Pulmonary Hypertension, Right Heart Failure & CTEPH Program, Temple University Hospital), and Dr. Marie-Louise Meng (Obstetric and Cardiothoracic Anesthesiology, Duke University) to discuss pregnancy and multidisciplinary critical care.

Three experts from varied subspecialties including Cardiology, Pulmonary Hypertension, Maternal Fetal Medicine, Cardiac Anesthesia and Obstetrical Anesthesia guide listeners through a case of a patient with a congenital conotruncal ventricular septal defect, Eisenmenger physiology, and pulmonary hypertension who becomes pregnant. The discussion touches on pre-conception risk assessment, pulmonary hypertension medical therapy in pregnancy, maternal monitoring during pregnancy, development of detailed multidisciplinary delivery plans and accessibility of such plans, and peri- and post-partum multidisciplinary management of high-risk patients.

Audio editing and episode introduction by CardioNerds Academy Intern, Christian Faaborg-Andersen.

Pearls • Notes • References • Guest Profiles • Production Team

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1. Cyanotic congenital heart disease presents multiple risks to the fetus, the most significant being intrauterine growth restriction. In a patient with Eisenmenger physiology, maternal oxygenation should be monitored closely throughout pregnancy, as hypoxia is often a marker of increased right to left shunting in these patients.
2. In patients with pulmonary hypertension, the RV-PA coupling relationship is the best indicator of maternal cardiovascular reserve through the pregnancy and post-partum period. The goal of therapy is to get the pulmonary vascular resistance down to a point where the right heart can adapt to that load and function either at a normal or a near-normal level.
3. When a high-risk patient meets with Anesthesia, it is important to consider the A’s: 1. Airway (anticipating any potential difficulties); 2. Access (whether this may present a challenge at the time of delivery); 3. Anxiety (specifically differentiating true hemodynamic changes in high-risk patients versus physiologic changes from anxiety); 4. Anticoagulation (knowledge of what agent the patient is on to determine safety of neuraxial anesthesia); 5. Availability (determining who else needs to be in the room, i.e. CT surgery, cardiothoracic anesthesia, ECMO team); 6. Arena (where is the safest place for this patient to deliver).
4. In patients with a shunt who undergo a Cesarean section, the uterus should not be exteriorized due to risk of venous micro air emboli.
5. As Dr. Forfia says, “panic is more dangerous sometimes than pulmonary hypertension!” Meaning, it is important to meet as a multidisciplinary team to develop a clear, easily accessible delivery plan for the patient. It is also prudent to have “everyone functioning in the environment they function best” like delivering the baby on the labor and delivery floor where all the necessary equipment and team members are available and bringing in other experts if needed rather than a cardiac operating room.

For a deep dive into Pregnancy & Pulmonary Hypertension, enjoy:

• Episode #124 with Dr. Candice Silversides.
• Episode #144 – Case Report: A Mother with Shortness of Breath

1. How does a multidisciplinary team play a role in the care for a high risk cardio-obstetrics patient, particularly one with congenital heart disease and pulmonary hypertension?

• According to the 2018 ESC guidelines, a multidisciplinary team is required to care for the pregnant patient with PH. This should include a PH expert at an experienced center for pregnancy and cardiac disease. Maternal outcomes in patients with PH have improved with targeted therapies as well as a multidisciplinary, team-based approach.
• A multidisciplinary team for a high-risk cardio-obstetrics patient should have representation from several subspecialties, typically including Cardiology (and in patients with PH, a PH expert should be included), Maternal Fetal Medicine, and Anesthesiology. Additional subspecialities can be added depending on the underlying diagnosis of the patient and any potential challenges anticipated at the time of delivery. (i.e. CT Surgery if ECMO may be needed).
• The key is consistent membership within the group for optimal team dynamics, working relationships, and continuity of patient care. Familiarity among group members helps to facilitate improved communication.
• Team members should be experienced in the care of high-risk cardio-obstetrics patients. As Dr. Forfia mentions during the podcast, panic can be the downfall of a well-functioning team in a high stake setting and is often dangerous to the patient.
• Frequent meetings should happen amongst group members to discuss patients and to form individualized, multidisciplinary delivery plans. The delivery plan should detail each aspect of labor and delivery, include the names and contact information of providers involved in the patient’s care, and should be easily accessible (ideally in a prominent location in the patient’s electronic medical record).
• If possible, providers should be allowed to work in their usual environment. For example, a high-risk patient should deliver on the L&D floor/L&D OR with OB/MFM and other members of the multidisciplinary team should come to that area. This ensures all necessary equipment and experienced staff will be present during the delivery.

2. What are the important considerations during the Anesthesia evaluation of a high-risk pregnant patient?

• When a high-risk patient meets with Anesthesia during pregnancy, the A’s should be considered, listed below:
• Airway: It is important to perform an assessment of the patient’s airway prior to delivery to anticipate any potential difficulties and to ensure that the appropriate equipment is available at the time of delivery if a difficult airway is anticipated.
• Access: Potential intravenous access sites should be assessed prior to delivery to determine whether access may present a challenge at the time of delivery.
• Anxiety: An Anesthesiologist for a high-risk patient should be adept at differentiating true hemodynamic alterations versus physiologic changes from anxiety to provide appropriate therapy and counseling.
• Anticoagulation: A subset of high-risk cardiac patients will be on chronic anticoagulation therapy during pregnancy. Knowledge of a patient’s anticoagulant is critical in determining the safety of neuraxial anesthesia. It is also important to highlight that Eisenmenger’s can lead to thrombocytopenia, which (if severe enough) can be a contraindication to neuraxial anesthesia.
• Availability: It is vital to determine who will need to be available for a high-risk patient’s delivery, particularly which specialists, but also which subspecialists (i.e. cardiac anesthesia, cardiologists with expertise in pulmonary hypertension, ECMO team etc.). This allows adequate planning and staffing at the time of delivery.
• Arena: The multidisciplinary team should discuss the best place for the patient to deliver (i.e. the L&D floor, L&D OR, cardiac OR) depending on the expected course of delivery. Often, it is best to have the patient delivery on a dedicated obstetrical floor and bring any necessary consultants there to ensure all necessary equipment for the delivery and experienced obstetrical staff are present.

3. What are some pearls for the multidisciplinary management of high-risk cardio-obstetrics patients and specifically those with pulmonary hypertension and a shunt lesion during delivery?

• As mentioned previously, a detailed delivery plan should be created in advance of delivery with input from the multidisciplinary team caring for the patient. This should be easily accessible by all team members at the time of delivery.
• Most of these patients should deliver by 37 weeks gestation at a center with cardiology and intensive care unit support if needed.
• Patients with pulmonary hypertension should avoid Valsalva/pushing as much as possible. This is accomplished by an assisted second stage of labor.
• Patients with uncorrected cyanotic congenital heart disease should be considered for antibiotic prophylaxis for endocarditis at the time of delivery.
• In patients with an intracardiac shunt, all intravenous lines should have filters to prevent paradoxical air embolism. Additionally, the OB team should avoid “exteriorizing” the uterus during a C-section due to risk of paradoxical air embolism. This is particularly important in right-to-left shunt lesions.
• Fetal heart rate can serve as the “5th vital sign” of the mother during the time of delivery and can add to the overall assessment of the mother and fetus.
• Specialized Anesthesia care may involve the insertion of a central line and/or arterial line for close hemodynamic monitoring during delivery and in the immediate post-partum period.

4. What are the interdisciplinary critical care considerations in the post-partum period for high-risk patients, and specifically those with pulmonary hypertension and shunt lesions?

• According to the 2018 ESC guidelines, the highest risk period is during puerperium and early post-partum where fluid shifts and hemodynamic changes are the greatest. As part of the delivery plan, immediate post-partum care should also be specified. Often high-risk patients may need to be monitored and managed in an ICU setting or on a Cardiology primary service with the OB/MFM, Anesthesiology, and Cardiology/PH teams participating in co-management.
• Meticulous fluid balance and optimization of RV function are important determinants of an optimal outcome in patients with PH who are post-partum.
• Frequent monitoring of volume status and oxygenation by experts in Cardiology and Pulmonary Hypertension is key in the early post-partum period in these patients. If progressive volume overload is seen, diuretics should be administered.
• Fluid mobilization in the early post-partum period is a cause of right ventricular volume overload and right heart failure and may lead to increased shunting.

5. If the unexpected happens, what are pearls for cardiac arrest in a pregnant patient?

• Cardiac arrest in the pregnant patient can have many possible causes. Initial steps including establishing IV access above the diaphragm, administering 100% oxygen, and relieving aortocaval compression with continuous left lateral displacement of the gravid uterus. This helps to improve maternal hemodynamics during compressions.
• The gravid uterus causes upward displacement of the internal organs. According to the AHA guidelines, chest compressions should be delivered with the patient supine, with constant left lateral displacement of the gravid uterus to relieve aortocaval compression. In the past, a 30-degree left lateral decubitus tilt was recommended, however it has been shown that this decreases the effectiveness of chest compressions and is therefore no longer recommended.
• If the patient was receiving IV Magnesium pre-arrest, this should be stopped, and IV/IO Calcium Chloride or Calcium Gluconate given.
• The pregnant patient’s airway undergoes significant changes during pregnancy, with increased friability and mucosal secretion. The upward displacement of internal organs also increases the risk of aspiration. The upward shift of the diaphragm leads to decreased functional residual capacity, increased metabolic demand, and potentially faster desaturation.
• Defibrillation doses and standard ACLS medication doses remain the same in the pregnant patient. During a cardiac arrest, no medications should be withheld for concerns of teratogenicity.
• If the pregnant patient does not respond to intervention and lacks return of spontaneous circulation, Cesarean section must be considered immediately within the first 4-5 minutes of CPR for optimal maternal and fetal outcomes. This should be done at the site of the cardiac arrest if it was an in-hospital cardiac arrest.

1. Li Q, Dimopoulos K, Liu T, et al. Peripartum outcomes in a large population of women with pulmonary arterial hypertension associated with congenital heart disease. Eur J Prev Cardiol. 2019; 26:1067-1076.

2. Presbitero P, Somerville J, Stone S, Aruta E, Spiegelhalter D, Rabajoli F. Pregnancy in cyanotic congenital heart disease. Outcome of mother and fetus. Circulation. 1994; 89:2673 – 2676.

3. Regitz-Zagrosek V, Roos-Hesselink J.W., Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy: the task force for the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC). Eur Hear J. 2018; 39:3165-3241.

4. Jeejeebhoy FM, et al. Cardiac arrest in pregnancy. A scientific statement from the American Heart Association. Circulation. 2015; 132: 1747-1773.

Dr. Kaitlyn Ibrahim has graduated cardiology fellowship from Temple University Hospital. She is currently a non-invasive cardiologist with a focus on women’s health as part of the Lankenau Heart Group.

Dr. Afshan Hameed is a Clinical Professor of both Cardiology and Maternal Fetal Medicine at the University of California, Irvine.  Dr. Hameed has served on multiple guideline committees on heart disease and pregnancy for the American College of Obstetrics and Gynecology and serves on the California Maternal Quality Care Collaborative (CMQCC) Pregnancy Associated Mortality Review Advisory Committee (PAMR) that reviews all cases of maternal mortality to identify gaps in care for quality improvement opportunities. She also serves on the writing committee for the Heart Rhythm Society’s “Arrhythmias in Pregnancy Guidelines” and as an expert to help create an Obstetrics Basic Life Support curriculum to integrate into the American Heart Association Life Support Program.

Dr. Paul Forfia is a Professor of Medicine at Temple University Hospital and Co-Director of the Pulmonary Hypertension, Right Heart Failure, and CTEPH Program at Temple University Hospital. He is a renowned expert in the management of patients with right heart failure and PH and has grown the program at Temple to one of the largest in the country.

Dr. Marie-Louise Meng is an assistant professor of anesthesiology at Duke University who has completed additional fellowships in both obstetrical anesthesia and cardiothoracic anesthesia. She is also a physician-scientist researching the role of echocardiography and biomarkers in identifying women at risk of cardiovascular complications after pregnancies complicated by preeclampsia.

• Natalie Stokes, MD
• Sonia Shah, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Kushani Gajjar and Dr. Mitha Naik from the Allegheny Health Network for a walk along the Three Rivers Trail in Pittsburgh. They discuss a case of young woman in her third trimester of pregnancy with a known history of pulmonary arterial hypertension. The management of pulmonary hypertension in pregnancy and RV failure in the context of pregnancy is described. The E-CPR segment is provided by Dr. Nandita Scott, Co-Director Corrigan Women’s Heart Health Program and Cardiovascular Disease and Pregnancy Service at Massachusetts General Hospital. Special cameo appearance by Dr. Dani Crousillat.

If you’re a current internal medicine resident, interested in the intersection between medical education, cardiovascular disease and digital media, consider applying to the CardioNerds Academy using this link. The deadline for this application is October 15th 2021. Learn more by visiting the CardioNerds Academy page.

Claim free CME just for enjoying this episode! Disclosures: None

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A 33-year-old woman in the third trimester of pregnancy, with a known history of untreated PAH in the setting of TKI therapy, presents with shortness of breath. She is found to have PA pressure greater than systemic pressure with PASP >130. We describe the management of PH and RV failure in the context of a pregnancy. The patient was admitted to the ICU where a multidisciplinary team was mobilized, involving high risk ob-gyn, maternal fetal medicine, critical care, anesthesiology, and advanced heart failure. They began pulmonary vasodilators including treprostinil, tadalafil and inhaled nitric oxide. They also added inotropic and vasopressor support for right ventricular dysfunction with her severe PAH. Fetal heart monitoring was performed. PAH also led to worsening of known chronic thrombocytopenia in the setting of CML. HELLP syndrome was ruled out. The patient had preterm rupture of membranes at 32 weeks of gestation and the team pursued assisted vaginal delivery to prevent vagal response. Following successful delivery, the patient elected to undergo intra-uterine device placement. Post-delivery, vasopressors and inotropes were weaned, and she was discharged on treprostinil, ambrisentan and tadalafil. Thankfully both the mother and baby returned healthy and well at 1 month follow up.

• CMR
• CXR
• TTE
• TTE

1. Pulmonary Hypertension is defined as a mean pulmonary arterial pressure (mPAP) of >20mmHg. There are 5 major types of pulmonary hypertension. Risk modifiers include symptom burden, exercise capacity, presence of pericardial effusion, RV function and hemodynamics.
2. Multidisciplinary care teams are the key to achieving optimal pregnancy outcomes in patients with PH. It is critical to create a team of experts with experience in pulmonary hypertension and plan for constant communication before, during, and after pregnancy.
3. Pregnant women who are already on PAH therapy outpatient should continue them during pregnancy (under the direction of PH experts) except for endothelin receptor blockers which fall in pregnancy category X.
4. PH during pregnancy is associated with up to 38% maternal mortality rate as the right ventricle (RV) is often unable to handle the volume shifts and hemodynamic changes that occur during pregnancy, labor, and delivery.
5. Patients with RV failure leading to low cardiac output and hypotension, like in this case, may benefit from vasopressors with the goal to maintain systemic blood pressure above pulmonary arterial pressures, preserving right coronary blood flow and preventing intracardiac shunting. Swan-guided management may be useful – to titrate inotropes and vasopressors, optimize pulmonary vasodilators and ensure that the patient is being adequately fluid-optimized to maintain a CVP of around 8-10.

1. What are the different types of pulmonary hypertension (PH)?
The WHO separates PH into 5 groups:

2. What is the role of TTE and RHC in the workup of PH?

• Tyrosine kinase inhibitors are known to cause PAH and there should be a low threshold to do screening TTEs in these patients when there is concern for the development of PAH.
• Echocardiogram is essential in the evaluation of PH –for positing the presence of PH, evaluating the left heart and congenital defects for clues to PH etiology, and assessing the structural consequences of PH on the right heart. In addition to estimating the pulmonary artery systolic pressure (PASP) by measuring the tricuspid regurgitant jet, we can characterize RV and RA size, RV function, and RV wall thickness, which may help both support the diagnosis and gauge prognosis for PH. Further, we can evaluate for left-sided heart disease contributing to PH. The presence of a pericardial effusion is a poor prognostic sign in those with pulmonary hypertension. Notably, the PASP is not of prognostic value due both to inaccuracies in measurement and falling values in the context of severe PH with failing RV function; a such PASP should not be used to surveil patients with PH or monitor response to PH therapies.

McLaughlin et al suggest using a checklist in the echocardiographic assessment of PH which includes the following1:

• Right heart catheterization is necessary to confirm the diagnosis of PH. The updated hemodynamic definition of PH hinges on accurate hemodynamic assessment. In a PH crisis, such as our patient, it is also important to delineate the impact of PH on the RV. Invasive hemodynamic testing is the gold standard for differentiating isolated precapillary, isolated postcapillary and combined pre and post capillary PH (see table below).

When we consider the hemodynamic profiles of pulmonary hypertension, we break down PH into isolated pre-capillary, isolated post-capillary, or combined pre-and post-capillary pulmonary hypertension as shows in the table below.

Furthermore, we can determine if a patient is “vasodilator responsive.” In the catheterization lab, a positive vasodilator response is defined as a decrease in mPAP ≥ 10 mmHg to an absolute value of ≤ 40 mmHg (without a decrease in cardiac output) with the use of inhaled nitric oxide or IV epoprostenol. If a patient has positive vasodilator test, calcium channel blockers can be initiated, however not all patients will be long term responders. We tend to do vasoreactivity testing in patients with PAH and not for other forms of PH (e.g., Pulmonary Veno-Occlusive Disease or Groups 2, 3, 4, or 5).

3. What are PAH-specific pharmacologic treatments?

• Remember that PAH is fundamentally a disease of increased pulmonary vascular resistance (PVR) causing elevated pulmonary pressures. The consequence of increased PVR includes increased RV afterload and hypoxemia and the subsequent clinical manifestations of PAH. Normally, the pulmonary vascular bed has a balance between vasodilators and vasoconstrictors that maintain a low-resistance, high-compliance state. This balance is disturbed in PAH and the goal of therapy is to “restore” balance between vasodilation and vasoconstriction.
• The management of PAH relies on 3 primary medication groups1:

Also remember calcium channel blockers in vasodilator responsive patients with PAH!

Other aspects of pharmacologic PAH treatment not discussed here include diuretics, digoxin, and oral anticoagulation, especially for patients with more advanced disease and on continuous parenteral prostacyclin therapy due to microthrombi in pulmonary arterioles.

4. What is the impact of pregnancy in PH?

• Prevalence of pulmonary hypertension has been rising due to the number of patient with congenital heart disease living to childbearing age, as well as the emergence of effective pulmonary vascular therapy.2,3
• According to one widely quoted systemic analysis, although a publication bias cannot be excluded, overall maternal mortality was significantly lower compared with previous era (25 vs. 38%, P = 0.047). Seventy-eight per cent of deaths occurred within the first month after delivery. Primigravidae and parturients who received general anesthesia were at higher risk of death. Maternal mortality in parturients with PAH remains prohibitively high, despite lower death rates than in previous decades. Early counseling regarding pregnancy risks, including contraception, remains paramount. Women with PAH who become pregnant warrant a multidisciplinary approach with consideration of advanced therapies and discussion of pregnancy termination.3-5
• Morbidity and mortality were highest in women with idiopathic PH, and lowest in women with PH due to left sided heart disease. Complications were also higher in patient with severe PH (RVSP >70mmHg).7
• A comprehensive study looking at approximately 1500 pregnant women with PH from the national inpatient sample (spanning from 2003-2012) found that the rate of major adverse cardiovascular events was around 24.8%.6
• Overall mortality for PH patients during pregnancy is quite high, up to 50%. The majority of patients died within the first month after delivery and major causes of death were heart failure, sudden cardiac death and pulmonary embolism4,5,8
• Complications of PH during pregnancy:
  • The normal physiologic changes of pregnancy (increased plasma volume, increased stroke volume, increased cardiac output, decreased systemic vascular resistance), are poorly tolerated in PH due to an inability to decrease pulmonary vascular resistance and accommodate the increased pulmonary flow. This can lead to increased right ventricular overload.
  • Decrease in systemic vascular resistance and associated drop in blood pressure can also lead to decreased RV perfusion leading to RV failure.
  • Pregnancy is both a prothrombotic and a pro-arrhythmic state, and maternal morbidity and mortality may also be related to complications from veous thromboembolism and arrhythmias.
  • Abnormal maternal hemodynamics in PH also contribute to increased fetal and neonatal complications including preterm birth as well as fetal and neonatal death.

5. What are some of the most important delivery considerations to keep in mind for these patients?

• Delivery timing and location: Consider delivering most patients by 37 weeks of gestation, if not earlier, depending on the stability of the patient. While some women may be followed in obstetric hospitals, delivery should take place in a location with backup of a cardiology, critical care, and advanced heart failure teams. 8
• Mode of delivery: If women are stable, assisted vaginal delivery is preferred as it is associated with fewer complications. 8
• Monitoring: In conjunction with OB consider the use of an arterial line for invasive blood pressure monitoring, central access for IV medication administration etc. A PA catheter may be necessary to optimize PAH therapy and RV support.8 Be wary of increased vascular fragility and the increased risk of complications of invasive vascular procedures during pregnancy.
• Anesthesia: Epidural anesthesia with good pain management is preferred (to avoid sympathetic surge from pain), with avoidance of general anesthesia if possible (as GA is associated with greater complications in patients with PH)8
• VA-ECMO: If concerns for patient destabilization arise, VA-ECMO should be initiated. 8

Post-partum: The majority of complications occur after delivery, with the first week posing the highest risk period. Close monitoring must be initiated, preferably in a CCU/ICU for several days post-delivery. Early diuresis is paramount, as fluid mobilization after delivery can lead to fluid overload and right heart failure.  8

1. McLaughlin, V.V., Shah, S.J., Souza, R. and Humbert, M., 2015. Management of pulmonary arterial hypertension. Journal of the American College of Cardiology, 65(18), pp.1976-1997.

2. Meng, M.L., Landau, R., Viktorsdottir, O., Banayan, J., Grant, T., Bateman, B., Smiley, R. and Reitman, E., 2017. Pulmonary hypertension in pregnancy. Obstetrics & Gynecology, 129(3), pp.511-520.

3. Lima, F.V., Yang, J., Xu, J. and Stergiopoulos, K., 2017. National trends and in-hospital outcomes in pregnant women with heart disease in the United States. The American journal of cardiology, 119(10), pp.1694-1700.

4. Bedard, E., Dimopoulos, K. and Gatzoulis, M.A., 2009. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension?. European heart journal, 30(3), pp.256-265.

5. Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: A systematic overview from 1978 through 1996. J Am Coll Cardiol. Published online 1998. doi:10.1016/S0735-1097(98)00162-4

6. Thomas E, Yang J, Xu J, Lima F V., Stergiopoulos K. Pulmonary hypertension and pregnancy outcomes: Insights from the national inpatient sample. J Am Heart Assoc. Published online 2017. doi:10.1161/JAHA.117.006144

7. Sliwa K, van Hagen IM, Budts W, et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology. Eur J Heart Fail. Published online 2016. doi:10.1002/ejhf.594

8. Martin, S.R. and Edwards, A., 2019. Pulmonary hypertension and pregnancy. Obstetrics & Gynecology, 134(5), pp.974-987.

• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD

CardioNerds (Amit Goyal & Karan Desai) join University of Minnesota fellows, Dr. Julie Power, Dr. Sasha Prisco, and Dr. Abdisamad Ibrahim for a riveting discussion in which they were pressured to diagnose a young woman with syncope. The fellows expertly take us through the next steps in the differential diagnosis, and management of pulmonary hypertension in this young patient! University of Minnesota faculty and expert in right ventricular (RV) failure in pulmonary arterial hypertension (PAH) Dr. Kurt Prins provides the E-CPR for this episode.

With this episode, the CardioNerds family warmly welcomes The University of Minnesota to the CardioNerds Healy Honor Roll. The CardioNerds Healy Honor Roll programs support and foster the the CardioNerds spirit and mission of democratizing cardiovascular education. Healy Honor Roll programs nominate fellows from their program who are highly motivated and are passionate about medical education. The University of Minnesota fellowship program director, Dr. Jane Chen has nominated Dr. Julie Power for this position. In addition to being a CardioNerds Ambassador, Julie has already done amazing CardioNerds work as part of the CardioNerds Academy fellowship.

Claim free CME just for enjoying this episode! Disclosures: None

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A Somali woman in her mid-30s with no significant past medical history presented with shortness of breath and exertional syncope. EKG revealed evidence of RV strain. CTA-PE protocol did not show PE. However, there was RV dilation and subsequent echocardiogram demonstrated normal LV, but moderately reduced RV function with evidence of RV pressure and volume overload. RVSP was estimated to be 188 mmHg!

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A. CXR, B. ECG, C. PA measurements: Main PA measures 2.4 cm, right PA measures 2.3 cm, left PA measures 1.9 cm, D. Tricuspid valve Doppler, E. RA tracing, F. RV tracing, G. PA tracing, H. Wedge tracing

1. Pulmonary hypertension (PH) can generally be categorized as pre-, post-, or combined pre- and post-capillary PH. Isolated pre-capillary pulmonary hypertension is characterized by: mean pulmonary artery pressure (mPAP) ≥ 20 mmHg, a pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and a pulmonary vascular resistance (PVR) ≥ 3 Woods units (WU). Pulmonary arterial hypertension (PAH) (WHO Group 1) falls under pre-capillary pulmonary hypertension.
   
2. Schistosomiasis is the most common cause of PAH (WHO Group I) worldwide. Approximately 7% of patient with hepatosplenic schistosomiasis have PAH. Some studies suggest that treatment of with praziquantel reverses vascular remodeling; however, there is point of no return, beyond which, anthelmintic therapies are ineffective to prevent progression.
   
3. Exertional syncope and pericardial effusion are both risk factors for higher mortality in PAH.
   
4. Women with severe PAH have extremely high risk of maternal morbidity and mortality. Endothelin receptor antagonists are contraindicated in pregnancy due to teratogenicity. Therefore, a pregnancy test must be obtained monthly while on this therapy.
   
5. Patients with a lower socioeconomic status, based on median household income, have more advanced PAH at the time of diagnosis.

1. How do you approach syncope?

Syncope is a sudden transient loss of consciousness associated with absence of postural tone followed by complete and usually rapid recovery. There should be not be clinical evidence of “non-syncope” conditions including seizures, hypoglycemia, drug or alcohol intoxication, concussion due to head trauma and so forth.

• One approach to determining the etiology of the syncope is to consider 4 major categories: orthostatic, reflex-mediated, cardiac-obstructive, or cardiac-electrical.
• Reflex-mediated (neurocardiogenic) syncope typically has a prodrome and encompasses vasovagal syncope, situational syncope, and carotid hypersensitivity.
• Orthostatic syncope is syncope occurring when rising from recumbency. It is generally associated with an orthostatic SBP drop by more than 20 mmHg or DBP drop by more than 10 mmHg with a compensatory rise in heart rate. We most commonly think of dehydration or hypovolemia causing orthostasis. Being post prandial can cause orthostasis as well. Neurogenic orthostatic hypotension (OH) involves excessive pooling of blood volume in the splanchnic and/or leg circulation. Upon standing, there is decreased venous return to the heart with a subsequent decrease in cardiac output and cerebral perfusion. The autonomic nervous system can typically increase vascular tone, inotropy and chronotropy; however, in neurogenic OH these mechanisms are inadequate. Conditions where neurogenic OH is relatively common include multiple system atrophy, Parkinson’s disease, Huntington’s disease, peripheral neuropathies (e.g., diabetes, amyloidosis), and spinal cord injury, amongst other etiologies. Finally, common medications associated with orthostatic syncope include diuretics, alpha blockers, and tricyclic antidepressants.
• Cardiac-obstructive syncope may occur from structural obstruction (i.e., aortic stenosis, HCM, mitral stenosis, pulmonary embolism) or other lesions which limit the stroke volume (i.e., pericardial tamponade, pulmonary hypertension.
• Cardiac-electrical syncope include both tachyarrhythmias and bradyarrhythmias, often without a prodrome.

2. What are the different types of pulmonary hypertension (PH)? What are the hemodynamic definitions of pulmonary hypertension?

• The WHO separates PH into 5 groups:
  • Group 1: Pulmonary arterial hypertension (e.g., idiopathic, heritable [BMPR2], anorexigen associated, drug or toxin-associated, HIV, connective tissue disease associated, schistosomiasis, portal hypertension, congenital heart disease, amongst other causes)
  • Group 2: Pulmonary hypertension due to left sided heart disease (e.g., HFrEF, HFpEF, left-side valvular heart disease)
  • Group 3: Pulmonary hypertension due to lung disease or hypoxia: (e.g.,COPD, ILD, OSA, hypoxia without lung disease such as high altitude, developmental lung disorders)
  • Group 4: PH due to pulmonary artery obstructions most commonly Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
  • Group 5: Multifactorial causes such as hematologic disorders (chronic hemolytic anemia, as with myeloproliferative disorders), metabolic disorders (e.g., Gaucher disease, glycogen storage diseases, CKD), and systemic disorders (e.g., pulmonary Langerhans cell histiocytosis, neurofibromatosis, sarcoidosis)

When we consider the hemodynamics of pulmonary hypertension, we break down PH into isolated pre-capillary, isolated post-capillary, or combined pre-and post-capillary pulmonary hypertension.

PAH falls under pre-capillary pulmonary hypertension, which is defined as mean pulmonary artery pressure (mPAP) ≥ 20 mmHg, a pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and a pulmonary vascular resistance (PVR) ≥ 3 Woods units (WU).

3. How do you work up suspected PAH?

• To start investigating for PAH, as always, we start with a thorough history and physical. The most common presenting symptom of pulmonary hypertension in general is exertional dyspnea/reduced exercise tolerance. Symptoms of PH can be nonspecific, especially early in its course, and thus there can be a delay in diagnosis. Remember, some patients have increased risk of developing PH and should be screened. These are patients with known risk factors for developing PAH, including relatives of patients with BMPR2 mutations, HIV, connective tissue disease (especially systemic sclerosis), portal hypertension, etc.
• Other accompanying symptoms may include chest pain, fatigue, and lightheadedness. Manifestations of more advanced disease include syncope, abdominal distension, and significant lower extremity edema attributable to right ventricular (RV) failure.
• Physical exam may reveal a loud P2, murmur of tricuspid regurgitation, an RV S3, jugular venous distension with or without Kussmaul’s sign, liver pulsatility, ascites, and/or peripheral edema.
• Review the CXR and EKG for findings consistent with pulmonary hypertension. Common EKG findings include right atrial enlargement, right axis deviation, RBBB, and an RV strain pattern in the right precordial leads. Findings on chest X-ray may include enlarged main and hilar pulmonary arteries (with loss of the peripheral blood vessels) and RV enlargement.
• Basic lab work should include a CBC with differential, biochemistry, TFTs, and HIV. The patient’s clinical presentation could lead you to screen for serologic evidence of connective tissue disorders or hepatitis. Cardiac biomarkers, including NT-proBNP, may have a role in prognosis and treatment response.
• Echocardiogram is essential in the evaluation of PH. In addition to estimating the pulmonary artery systolic pressure (PASP) by measuring the tricuspid regurgitant jet, we can characterize RV and RA size, RV function, and RV wall thickness, which may help both support the diagnosis and gauge prognosis for PH. Further, we can evaluate for left-sided heart disease contributing to PH. The presence of a pericardial effusion is a poor prognostic sign. 
• PFTs, overnight oximetry with blood gases, and CT chest can help delineate the relative contribution of pulmonary disease to the patient’s PH disease (WHO Group 3). VQ scan can rule out a diagnosis of CTEPH with high sensitivity (WHO Group 4).
• Right heart catheterization is necessary to confirm the diagnosis of PH. Furthermore, we can determine if a patient is “vasodilator responsive.” In the catheterization lab, a positive vasodilator response is defined as a decrease in mPAP ≥ 10 mmHg to an absolute value of ≤ 40 mmHg (without a decrease in cardiac output) with the use of inhaled nitric oxide or IV epoprostenol. If a patient has positive vasodilator test, calcium channel blockers can be initiated, however not all patients will be long term responders. We tend to do vasoreactivity testing in patients with PAH and not for other forms of PH (e.g., Pulmonary Veno-Occlusive Disease or Groups 2, 3, 4, or 5).

4. What are PAH specific pharmacologic treatments?

• Remember that PAH is fundamentally a disease of increased pulmonary vascular resistance (PVR) causing elevated pulmonary pressures. The consequence of increased PVR includes increased RV afterload and hypoxemia and the subsequent clinical manifestations of PAH. Normally, the pulmonary vascular bed has a balance between vasodilators and vasoconstrictors that can maintain a low-resistance, high-compliance state. This balance is disturbed in PAH and the goal of therapy is to “restore” balance between vasodilation and vasoconstriction.
• The management of PAH has 3 medication groups:
  • Nitric oxide pathway:
    • PDE5 inhibitors: Sildenafil and tadalafil. These medications prevent the breakdown of cGMP which mediates the potent vasodilator and inhibitor of platelet aggregation, nitric oxide. The most common side effect for these medications is headache. Remember these medications should not be taken with nitrates!
    • Soluble guanylate cyclase (sGC) stimulators: riociguat. These medications stimulate sGC and thus increase sensitivity to NO. Riociguat is primarily used in CTEPH, but can also be used in PAH (PATENT-1 and -2 Trials) including PAH associated with sickle cell disease
  • Endothelin-1 (ET-1) pathway:
    • Endothelin receptor antagonists (ERAs): macitentan, bosentan, ambrisentan. Endothelin-1 is produced by endothelial cells and acts on two receptors, endothelin receptor A (ET-A) and endothelin receptor B (ET-B). ET-A is expressed on vascular smooth muscle cells and ET-B on both smooth muscle cells and endothelial cells. Stimulation of both receptors tends to lead to vasoconstriction, while stimulation of ET-B leads to vasodilation. ERAs antagonize these receptors to shift the balance towards vasodilation (e.g., bosentan is a dual ET-A/ET-B antagonist and ambrisentan is a more selective ET-A antagonist). Common side effects are lower extremity edema and hepatotoxicity. NOTE: patient should not get pregnant on ERAs because of teratogenicity!
  • Prostacyclin Pathway
    • Prostacyclin analogs: epoprostenol, iloprost, treprostinil. Prostacyclin is a potent endogenous vasodilator and inhibits platelet aggregation. This class of medications have PO, SQ, IV, and inhaled formulations. Common side effects include headache, diarrhea, nausea, and jaw pain.
    • PCA-receptor agonist: selexipag (oral).

Also remember CCB in vasodilator responsive patients with PAH!

Other aspects of pharmacologic PAH treatment not discussed here include diuretics, digoxin, and oral anticoagulation, especially for patients with more advanced disease and on continuous parenteral prostacyclin therapy due to microthrombi in pulmonary arterioles.

5.How do we risk stratify PAH patients and response to treatment?

• The REVEAL 2.0 risk score helps determine 1 year mortality based on WHO group, renal function, functional class, age, heart rate, 6 minute walk test, BNP, presence of pericardial effusion of echocardiogram, PFTs, and RHC values.
• Patients should also undergo routine 6 minute walk test and/or cardiopulmonary exercise test to assess their functional status and response to medications. Biomarkers may be helpful to assess treatment response. Echocardiography and RHC may be used every 6 to 12 months in patients with unstable or deteriorating symptoms to guide therapy and then considered on a case-by-case basis in stable patients.

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• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD