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The modern CICU has evolved to include patients with complex pulmonary mechanics requiring more non-invasive and mechanical ventilation. Series co-chairs Dr. Eunice Dugan and Dr. Karan Desai along with CardioNerds Co-founder Dr. Amit Goyal were joined by FIT lead, Dr. Sam Brusca, who has completed his NIH Critical Care and UCSF Cardiology fellow and currently faculty at USCF. We were fortunate enough to have two expert discussants: Dr. Burton Lee, Head of Medical Education and Global Critical Care within the National Institutes of Health Critical Care Medicine Department and master clinician educator with the ATS Scholar’s Critical Care for Non-Intensivists program, and Dr. Chris Barnett, ACC Critical Care Cardiology council member and Section Chair of Critical Care Cardiology at UCSF.  In this episode, these experts discuss the basics of mechanical ventilation, including the physiology/pathophysiology of negative and positive pressure breathing, a review of ventilator modes, and a framework for outlining the goals of mechanical ventilation. They proceed to apply these principles to patients in the CICU, specifically focusing on patients with RV predominant failure due to pulmonary hypertension and patients with LV predominant failure. Audio editing by CardioNerds Academy Intern, student doctor, Shivani Reddy.

The CardioNerds Cardiac Critical Care 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. Mark Belkin, Dr. Eunice Dugan, Dr. Karan Desai, and Dr. Yoav Karpenshif.

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• Respiratory distress, during spontaneous negative pressure breathing can lead to high transpulmonary pressures and potentially large tidal volumes. This will increase both RV afterload (by increasing pulmonary vascular resistance) and LV afterload (by increasing LV wall stress).

• An analogy for the impact of negative pleural pressure during spontaneous respiration on LV function is that of a person jumping over a hurdle. The height of the hurdle does not increase, but the ground starts to sink, so it is still harder to jump over.

• Intubation in patients with right ventricular failure is a tenuous situation, especially in patients with chronic RV failure and remodeling (increased RV thickness, perfusion predominantly during diastole, RV pressure near or higher than systemic pressure). The key tenant to safe intubation is avoiding hypotension, utilizing induction agents such as ketamine or etomidate, infusing pressors, and potentially even performing awake intubations.

• Non-invasive positive pressure ventilation in HFrEF has hemodynamic effects similar to a cocktail of IV inotropes, dilators, and diuretics. CPAP decreases pulmonary capillary wedge pressure (LV preload), decreases systemic vascular resistance (afterload), and increases cardiac output.

• Airway pressure during mechanical ventilation is based on the “equation of motion”: Pressure = Volume/Compliance + Flow*Resistance + PEEP.

• Our goals of oxygenation on mechanical ventilation include achieving acceptable PaO2/Sat with the lowest FiO2 possible (avoiding oxygen toxicity) and optimal PEEP (which increases oxygenation but can have detrimental impact on cardiac output)

• Our goals of ventilation on mechanical ventilation include achieving acceptable pH and PaCO2 while preventing ventilator induced lung injury and avoiding auto-PEEP. We prevent lung injury by reducing tidal volume (ideally <8cc/kg, plateau pressure < 30 cmH20, driving pressure < 15 cmH20) and auto-peep by reducing respiratory rate (and allowing for full expiration).

• No ventilator mode is “superior” to the others. What is most important is that providers are comfortable with the applied mode and able to appropriately respond to active changes in patient effort and mechanics.

1. What are the hemodynamic effects of Negative Pressure breathing in the RV and LV?

RV

– Negative pleural pressure is transmitted to pericardium and RV

– Negative pleural pressure is also transmitted to the pulmonary vasculature

– Thus, the pressure drop is net neutral across the RV-PA circuit and does not affect afterload

– However, large negative pleural pressure swings still lead to increased transpulmonary pressure, increased lung volumes, and associated increased PVR (RV afterload).

LV

– Negative pleural pressure is transmitted to the pericardium and LV

– Negative pleural pressure is NOT transmitted to the extra-thoracic aorta

– Transmural pressure across the LV increases and the gradient for flow from LV to distal aorta decreases (as LV pressure drops but distal aorta doesn’t)

– Overall, this increases LV afterload

What are the hemodynamic effects of Positive Pressure breathing on the RV and LV?

RV

– Positive pressure is transmitted to the pericardium and the RV

– Positive pressure is transmitted to the pulmonary vasculature

– Thus, the pressure increase is net neutral across the RV-PA circuit and does not affect afterload

– However, positive pressure and increased transpulmonary pressure with instilled flow/volume increases PVR (RV afterload)

– Notably, PVR and lung volume can graphically be illustrated as a U-shaped curve. PVR initially decreases as volume is instilled toward functional residual capacity (FRC), with traction of extra-alveolar vessels. As lung volume increases above FRC, PVR increases, with intra-alveolar vessel compression

LV

– Positive pressure is transmitted to the pericardium and the LV

– Positive pressure is NOT transmitted to the extra-thoracic aorta

– Transmural pressure across the LV decreases and the gradient for flow from LV to distal aorta increase (as LV pressure increases but distal aorta doesn’t)

– Overall, this decreases LV afterload

2. Is NIPPV useful in in patients with heart failure?

– Though studies have been inconsistent, there is likely a benefit (reducing intubation +/- mortality) for implementing NIPPV in acute decompensate heart failure

– Given the hemodynamic benefits outlined above, positive pressure administered via modalities such as CPAP and Bi-PAP improve LV function

– Preload decreases (positive pressure decreases inflow into the RA), Wedge pressure decreases, SVR decreases, and Cardiac output increases

– CPAP is primarily needed for oxygenation; however, Bi-PAP can augment ventilation and of-set increased work of breathing

– Importantly, NIPPV should not unnecessarily delay intubation in patients who are failing, as this delay likely increases mortality across patient populations.

3. What are the Oxygenation Goals of Mechanical Ventilation?

– To achieve acceptable PaO2 and SaO2 (>65 mmHg, >92-94%), whilst avoiding inspired oxygen toxicity (FiO2 > 60%)

– Oxygenation is primarily impacted by FiO2 and PEEP. PEEP can be titrated to aide in reducing FiO2, though can have negative impacts on cardiac output by reducing venous return

4. What are the Ventilation Goals of Mechanical Ventilation?

– To achieve acceptable PCO2 and pH without causing harm (ventilator induced lung injury)

– We avoid ventilator induced lung injury by reducing tidal volume (ideal < 8 cc/kg), reducing mechanical power (respiratory rate), reducing plateau pressure (< 30 cmH20), reducing driving pressure (< 15 cmH20), and reducing repeated alveolar opening/closing (by having adequate lung recruitment)

– Ventilation is primarily impacted by TV and respiratory rate, which equate to minute ventilation

5. How can we calculate Airway Pressure using the Equation of Motion as related to Mechanical Ventilation?

Airway Pressure = V/C + FxR + PEEP

V/C = TV/Compliance and represents the alveolar pressure of the lung generated by a given TV at a given static lung compliance

FxR = Flow x Resistance and is akin to Ohm’s law (V=IR), representing the pressure due to dynamic/resistive forces in the larger airways

PEEP is the pressure stating point at the beginning of the inspiration

6. What considerations need to be taken when intubating a patient with RV Failure/Pulmonary Hypertension?

– Intubation should be avoided if possible (though notably, respiratory distress and spontaneous breathing is not necessarily preferable, especially in the setting of respiratory acidosis or excessively low lung volumes)

– Reliable vascular access and in-line pressors are key to avoiding hypotension during induction

– Rapid sequence intubation (RSI) drugs such as etomidate and ketamine are preferred to propofol

– Awake intubation is safest if feasible

1. Alviar CL, Miller PE, McAreavey D, et al. Positive Pressure Ventilation in the Cardiac Intensive Care Unit. J Am Coll Cardiol. Sep 25 2018;72(13):1532-1553. doi:10.1016/j.jacc.2018.06.074

2. Barnett CF, O’Brien C, De Marco T. Critical care management of the patient with pulmonary hypertension. Eur Heart J Acute Cardiovasc Care. Jan 12 2022;11(1):77-83. doi:10.1093/ehjacc/zuab113

3. Bradley TD, Holloway RM, McLaughlin PR, Ross BL, Walters J, Liu PP. Cardiac output response to continuous positive airway pressure in congestive heart failure. Am Rev Respir Dis. Feb 1992;145(2 Pt 1):377-82. doi:10.1164/ajrccm/145.2_Pt_1.377

4. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. Jun 10 2004;350(24):2452-60. doi:10.1056/NEJMoa032736

5. Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. Oct 18 2016;316(15):1583-1589. doi:10.1001/jama.2016.11993

6. Investigators I-R, the A, New Zealand Intensive Care Society Clinical Trials G, et al. Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med. Mar 12 2020;382(11):989-998. doi:10.1056/NEJMoa1903297

7. Schjorring OL, Klitgaard TL, Perner A, et al. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med. Apr 8 2021;384(14):1301-1311. doi:10.1056/NEJMoa2032510

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.

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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

CardioNerds (Daniel Ambinder) and ACHD series co-chair Dr. Dan Clark discuss advanced heart failure therapies including mechanical circulatory support (MCS) and heart transplantation (HT) in patients with adult congenital heart disease (ACHD) with Dr. Rafael Alonso-Gonzalez, cardiologist and director of Adult Congenital Heart Disease program at the University of Toronto and ACHD fellow Dr. Andy Pistner (University of Washington). They cover epidemiology of heart failure in ACHD, outcomes after HT, unique challenges of HT in this population, impact of allocation policies on access to transplantation, and regionalization of advanced heart failure care. They also discuss a practical approach to advanced heart failure therapy evaluation in ACHD. Audio editing by CardioNerds Academy Intern, student doctor Adriana Mares.

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

This episode is made possible with support from Medmastery. At Medmastery you can learn some of the most important clinical skills like echo, advanced EKG, coronary angiography, PCI basics, pacemaker- and ICD troubleshooting and so much more. CardioNerds listeners can get an exclusive 15% discount on a lifetime subscription. Click HERE for details.

Pearls • Notes • References • Guest Profiles • Production Team

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1. Heart failure is a major comorbidity and the leading cause of death in adults with congenital heart disease.
2. Identification of advanced heart failure in ACHD is challenging. ACHD patients do not always self-identify exercise limitations or exertional dyspnea. Cardiopulmonary exercise testing is a useful tool in evaluating these patients.
3. Patients with ACHD awaiting heart transplantation are less likely than non-ACHD patients to receive a heart transplant, and ACHD patients have an increased risk of death or delisting while awaiting heart transplantation.
4. Evaluation of transplant candidacy and potential need for multi-organ transplantation in complex congenital heart disease (i.e., Fontan palliation) requires a multidisciplinary approach.
5. Regionalization of care improves outcomes for ACHD patients with advanced heart failure. High volume transplant centers have better early survival for ACHD patients after heart transplant, and the highest volume ACHD transplant centers in each UNOS region have better early survival.

1. How many ACHD patients have heart failure?

Patients with ACHD are a large and heterogeneous group. The signs and symptoms of heart failure vary widely depending on the underlying congenital heart disease. Patients with D-transposition of the great arteries repaired with an arterial switch operation have low rates of heart failure (~3%)1 compared to those patients Fontan palliation for single ventricle physiology (40%)2. Heart failure is the leading cause of death in patients with ACHD3,4.

2. How many patients with ACHD end up receiving a heart transplant or mechanical circulatory support?

Heart transplantation for congenital heart disease in adults has been increasing in frequency since the late 1980s. Between 2010 and 2012, this accounted for 4% of all adult heart transplants in the United States5. This represents a small fraction compared to the number of adults who die due to complications of heart failure related to congenital heart disease. In a recent study of the INTERMACs registry, 126 patients with ACHD from a total of 16,000 patients over a 10-year period underwent placement of durable mechanical support devices (ventricular assist device)6.

3. Why are these numbers low relative to the number of ACHD patients with heart failure?

Identification of those patients with ACHD who are at risk for adverse outcomes related to heart failure is challenging. The symptoms of heart failure reported in these patients is often different from what is described in patients with acquired heart failure. Similarly, having grown up with reduced aerobic capacity, many of these patients do not self-identify exercise limitations or exertional dyspnea7.

The organ allocation policies that are used to prioritize patients for transplant also contribute to this situation. Patients with ACHD on the heart transplant wait-list are less likely than their non-ACHD counterparts to receive a transplant. This difference persists regardless of initial urgency listing status8. Secondly, patients with ACHD are more likely to die or be delisted (presumably due to clinical deterioration) while awaiting heart transplantation9. The US heart allocation policies have recently been updated, which may improve access to heart transplantation in this population.

Other barriers to heart transplantation in patients with ACHD include allosensitization (development of antibodies against potential donor antigens), donor-recipient size matching, psychosocial barriers, and anatomic or other surgical challenges. Lastly, there are few providers with training in both advanced heart failure and adult congenital heart disease to integrate the evaluations necessary to identify suitable candidates for transplantation.

4. How do patients with ACHD do after heart transplantation?

Patients with ACHD have a worse early mortality after heart transplant (up to 1 year) compared to those patients without ACHD10. However, early survival after heart transplantation in ACHD has been improving over the past 20 years11. Additionally, those patients with ACHD who survive past the first year after heart transplantation have improved survival compared to patients without congenital heart disease.

More recently, we have found that that patients with ACHD undergoing heart transplant at high-volume centers (>38 transplants per year) have improved early survival compared to low-volume centers (<14 transplants per year)12. Overall survival is also improved when heart transplantation is performed at the highest volume ACHD transplant center in the UNOS region when compared to all the other transplant centers13. This idea of regionalization of care holds promise for transplant outcomes in this population.

Khairy P, Clair M, Fernandes SM, et al. Cardiovascular outcomes after the arterial switch operation for D-transposition of the great arteries. Circulation. Jan 22 2013;127(3):331-9. doi:10.1161/CIRCULATIONAHA.112.135046

Piran S, Veldtman G, Siu S, Webb GD, Liu PP. Heart failure and ventricular dysfunction in patients with single or systemic right ventricles. Circulation. Mar 12 2002;105(10):1189-94. doi:10.1161/hc1002.105182

Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Mortality in adult congenital heart disease. Eur Heart J. May 2010;31(10):1220-9. doi:10.1093/eurheartj/ehq032

Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of death in adults with congenital heart disease. The American Journal of Cardiology. 2000;86(10):1111-1116. doi:10.1016/s0002-9149(00)01169-3

Maxwell BG, Wong JK, Sheikh AY, Lee PH, Lobato RL. Heart transplantation with or without prior mechanical circulatory support in adults with congenital heart disease. Eur J Cardiothorac Surg. May 2014;45(5):842-6. doi:10.1093/ejcts/ezt498

Cedars A, Vanderpluym C, Koehl D, Cantor R, Kutty S, Kirklin JK. An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of hospitalization, functional status, and mortality after mechanical circulatory support in adults with congenital heart disease. J Heart Lung Transplant. May 2018;37(5):619-630. doi:10.1016/j.healun.2017.11.010

Gratz A, Hess J, Hager A. Self-estimated physical functioning poorly predicts actual exercise capacity in adolescents and adults with congenital heart disease. Eur Heart J. Feb 2009;30(4):497-504. doi:10.1093/eurheartj/ehn531

Everitt MD, Donaldson AE, Stehlik J, et al. Would access to device therapies improve transplant outcomes for adults with congenital heart disease? Analysis of the United Network for Organ Sharing (UNOS). J Heart Lung Transplant. Apr 2011;30(4):395-401. doi:10.1016/j.healun.2010.09.008

Alshawabkeh LI, Hu N, Carter KD, et al. Wait-List Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation in the U.S. J Am Coll Cardiol. Aug 30 2016;68(9):908-17. doi:10.1016/j.jacc.2016.05.082

Menachem JN, Schlendorf KH, Mazurek JA, et al. Advanced Heart Failure in Adults With Congenital Heart Disease. JACC Heart Fail. Feb 2020;8(2):87-99. doi:10.1016/j.jchf.2019.08.012

Riggs KW, Zafar F, Radzi Y, Yu PJ, Bryant R, 3rd, Morales DLS. Adult Congenital Heart Disease: Current Early Expectations After Cardiac Transplantation. Ann Thorac Surg. Feb 2020;109(2):480-486. doi:10.1016/j.athoracsur.2019.06.067

Menachem JN, Lindenfeld J, Schlendorf K, et al. Center volume and post-transplant survival among adults with congenital heart disease. J Heart Lung Transplant. Nov 2018;37(11):1351-1360. doi:10.1016/j.healun.2018.07.007

Nguyen VP, Dolgner SJ, Dardas TF, Verrier ED, McMullan DM, Krieger EV. Improved Outcomes of Heart Transplantation in Adults With Congenital Heart Disease Receiving Regionalized Care. J Am Coll Cardiol. Dec 10 2019;74(23):2908-2918. doi:10.1016/j.jacc.2019.09.062

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 Goyal), Dr. Colin Blumenthal (CardioNerds Academy House Faculty Leader and FIT at the University of Pennsylvania), and Dr. Anjali Wagle (CardioNerds Ambassador and FIT at Johns Hopkins University), discuss the baseline assessment of stroke and bleeding risk in patients with atrial fibrillation (AF) with Dr. Elaine Hylek. Dr. Hylek is a professor of medicine at the Boston University School of Medicine and is the Director of the Thrombosis and Anticoagulation Service at Boston Medical Center. Stroke is a potentially devastating and preventable complication of AF. Understanding the balance between stroke and bleeding risk is crucial in determining who should be on anticoagulation. Join us to discuss this topic! In the next episode of the series, we will discuss situational risk assessment in the context of peri-cardioversion, peri-procedural status, triggered atrial fibrillation, and more. Audio editing by CardioNerds Academy Intern, Pace Wetstein.

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. Hylek discloses grant and research support from Medtronic and Janssen, and honoraria and/or consulting fees from Boehringer Ingelheim, and Bayer.

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

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Notes drafted by Dr. Anjali Wagle

1. Why do strokes happen in atrial fibrillation? Why is reducing stroke risk so important?

Atrial fibrillation is associated with a significantly increased risk of stroke. The mortality of strokes related to AF have been estimated to be around 25% at 30 days in early studies which included either persistent or permanent AF, though of note, these studied were biased towards larger strokes since the diagnosis was based on physical exam and not high resolution imaging.

AF promotes thrombogenesis through Virchow’s triad which includes:

In atrial fibrillation, patients usually have a dilated left atrium and decreased blood flow through the atrial appendage which contribute to thrombogenesis.

Multiple risk scores have been derived (i.e., CHA2DS2VASc) for estimation of stroke risk in patient with AF to identify whom to treat with anticoagulation to reduce the stroke risk.

2. How were CHADS2 and CHA2DS2VASc (CV) created and validated?

The CHADS2 score was derived in 2001 by Gage et al from data including hospitalized patients with nonrheumatic AF who were not prescribed warfarin at hospitalized discharge. The CHADS2 score assigns one point to congestive heart failure, hypertension, age ≥ 75 years, and diabetes mellitus and two points to a previous history of stroke or transient ischemic attack (TIA) for a total of 6 points. Stroke rate per 100 patient-years rose by a factor of 1.5 for each 1-point increase in the CHADS2 score.

However, it was found that there were several limitations associated with the CHADS2 score including that more than half of the patients were classified as moderate risk, making it unclear if antiplatelet or anticoagulation should be used in this population. Additionally, there were other “minor” risk factors (female sex, CAD, age 65-74) that were not included in the score.

In 2010, Lip et al proposed the CHA2DS2VASc score that included these three additional factors: female gender, vascular events, and age 65-74. These additions to the original CHADS2 score allowed the CHA2DS2VASc score to reclassify patients in the moderate risk group into either the high or low risk groups (CV <1 or >2), making the decision of when to start anticoagulation easier.

Some weaknesses of the CV score include that the individual factors are binary. For example, one point for diabetes does not discriminate risk based on if the patient’s A1c is 14 vs. 7. Similarly, the score is static and assumes the risk from each risk factor doesn’t change over time even though the endothelial dysfunction caused by a specific disease state isn’t fixed. Additionally, the C-statistic for the CV score is only 0.6 with newer scores that are more accurate including such as GARFIELD-AF (but these newer scores are less user friendly). That being said, the score still does a very good job of differentiating between high and low risk patients, which is the most important clinical question when deciding if someone needs anticoagulation.

3. Which populations were not studied in the validation of the CV score?

Many of these studies have woefully low enrollment of racially diverse populations. Additionally, patients with amyloidosis, moderate-severe MS, and HOCM have a baseline higher risk of stroke were excluded from these studies. Patients with bioprosthetic valves were also excluded from the original derivation though there is now limited data showing use of the CV is reasonable.

4. How does AF burden affect stroke risk? Is there a temporal association between AF and stroke?

Early trials did not find a temporal association between AF and stroke, though these trials often used physical exam definitions for stroke and current technology like implantable loop recorders (ILRs) didn’t exist to monitor 24/7. More modern studies like the TREND and KP-RHYTHM trials showed that stroke risk is related to AF burden. Longer episodes of AF seem to clearly be associated with stroke, but shorter episodes of AF aren’t as temporally related to stroke. In the LOOP trial use of ILRs to detect episodes of AF longer than 6 minutes led to a 3-fold increase in AF detection and initiation of AF, but did not reduce the number of strokes. This could indicate that there is some amount of AF that doesn’t require AC or that short runs of AF are associated with atrial myopathy that could be causing the strokes. It remains unclear what is the “chicken and egg” in this scenario.

5. How can we assess bleeding risk for patients with atrial fibrillation? How can we use these scores in our clinical practice?

Developed and published in 2010 by Pisters et al., the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly [age >65], medication predisposing to bleeding, excessive alcohol use) score aimed to create an easy to calculate and clinically meaningful score to estimate bleeding risk. It was validated using 3,978 patients from the Euro Heart Survey on AF and had good predictive accuracy (C-statistic 0.72). Of note, the score uses the less severe ISTH definition for a major hemorrhage, which doesn’t require as severe bleeding as the TIMI major bleeding definition.

Many of the factors that go into the score are dynamic (for example HTN is SBP > 160 and not a history of HTN). The intention was to alert the provider of potentially modifiable factors that could be addressed to lower bleeding risk (such as better BP control). This would reduce the patients HAS-BLED score and therefore their bleeding risk. There is no absolute cutoff where anticoagulation in AF would be considered prohibitive.

6. What is the approach for patients with borderline stroke risk with a CV of 1 in men or 2 in women?

Patients with a CV of 1 have between a 0.6% and a 0.9% risk of stroke/TIA/systemic embolism in a given year. That means even with a CV of 1 they have close to a 1/100 risk of an event in a given year. Given the high mortality and morbidity with embolic strokes and the lower incidence of major bleeding with modern DOACs, should have shared decision-making conversation with patients about starting AC at this risk level. One can consider other risk factors not in CV like LA function, appendage morphology, AF burden etc to help as tie breakers.

With the advent and rapid evolution of contemporary percutaneous coronary intervention (PCI), the early invasive management of acute myocardial infarction (AMI) has become a mainstay in therapy with significant impact on patient outcomes. However, despite modern advances in technology and system-based practices, AMI presenting with cardiogenic shock (CS) continues to portend a high risk of morbidity and mortality. Few randomized controlled clinical trials are available to guide decision-making in this uniquely challenging patient population. Understanding the pathophysiologic mechanism by which injury occurs and propagates the shock cycle can be instrumental in selecting an appropriate strategy for revascularization and left ventricular unloading. In this episode we are joined by Dr. Venu Menon, The Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine,  section head of clinical cardiology, fellowship program director, and director of the Cardiac intensive care unit at the Cleveland Clinic. Dr. Menon shares his wealth of knowledge and experience to help us review the contemporary data available for AMI CS management in a case-based discussion. We are also joined by Dr. Priya Kothapalli, star chief fellow and future interventionalist from University of Texas at Austin, series co-chair Dr. Yoav Karpenshif, and CardioNerds Co-founders Amit Goyal and Daniel Ambinder. Audio editing by CardioNerds Academy Intern, Dr. Christian Faaborg-Andersen.

The CardioNerds Cardiac Critical Care 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. Mark Belkin, Dr. Eunice Dugan, Dr. Karan Desai, and Dr. Yoav Karpenshif.

This episode is made possible with support from Medmastery. At Medmastery you can learn some of the most important clinical skills like echo, advanced EKG, coronary angiography, PCI basics, pacemaker- and ICD troubleshooting and so much more. CardioNerds listeners can get an exclusive 15% discount on a lifetime subscription. Click HERE for details.

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1. The H&P does matter! Age, location of infarction, heart rate, systolic blood pressure, and heart failure symptoms all carry weight in determining prognosis and risk of mortality.
2. Define functional status, comorbid conditions, and life expectancy to help guide clinical decision-making. Do a quick bedside echocardiogram if possible to elucidate the predominant mechanism driving CS and rule out mechanical complications.
3. Act with urgency! Get to the catheterization lab to characterize coronary anatomy and revascularize the culprit vessel as soon as possible.
4. Minimize/avoid the use of vasopressors; if needed, wean as quickly as possible to avoid worsening myocardial ischemia. Consider mechanical circulatory support early!
5. Despite dramatic advances in AMI management, data is limited in AMI CS management. Ask the important questions, get involved in the scientific inquiry as a trainee!

1. Why is it important to recognize AMI complicated by CS?

• AMI CS occurs in 7-10% of patients presenting with AMI and has a higher prevalence among elderly patients.
• The SHOCK trial (1999) showed significant survival benefit at 6 months with early revascularization with balloon angioplasty compared to medical therapy alone in AMI CS.
• Registry data suggests that early revascularization is beneficial in AMI CS even in elderly patients. Decision-making should be guided using a holistic view of the patient’s overall biology.
• Despite advances in revascularization techniques and availability of mechanical support, AMI CS portends a 40-45% risk of 30-day mortality in the modern era.
• Significant variation in management strategy exists between centers and data to guide decision-making is limited.
• The Society for Cardiovascular Angiography and Intervention (SCAI) classification system of shock stage may be helpful in characterizing patient risk and guiding clinical decision-making.

2.     Which patients with AMI CS should undergo invasive monitoring and revascularization? What should be the timing of any intervention?

• In viable patients presenting with AMI CS, the primary goal should be to get to the catheterization laboratory to characterize the anatomy and revascularize the culprit vessel as soon as possible.
• Patient history, physical exam, laboratory exam, and echocardiography, if available, are critical pieces of information that should be obtained without delaying catheterization laboratory transfer.
• Patients presenting in SCAI shock stages C-E may require stabilization pre-procedure while minimizing delays to revascularization.
• Anticipating potential sequelae (such as acute pulmonary edema with respiratory failure requiring intubation) is crucial to minimizing delays.
• Maintain adequate perfusion pre-procedure (goal mean arterial blood pressure of >65mmHg). Minimize use and avoid escalation of vasopressor or inotropic therapy, as these agents worsen myocardial ischemia.
• The prevalence of multivessel disease, left main or proximal left anterior descending artery disease in AMI CS is high. Revascularization with restoration of TIMI 3 flow as soon as possible should be the primary goal, regardless of strategy.

3.     When should mechanical circulatory support (MCS) be used in AMI CS?

• Immediate MCS may be beneficial in patients with persistent hemodynamic or electrical instability or patients at high risk for developing instability. MCS should be placed early and maintained until the shock cycle is reversed.
• If the primary mechanism for CS is left ventricular failure, an intra-aortic balloon pump (IABP) or transvalvular axial flow pump (Impella) may be considered. Additional strategies include venoarterial extracorporeal membrane oxygenation with left ventricular venting strategy or TandemHeart percutaneous assist device.
• There is limited data regarding the role of MCS in AMI; this is an area of active clinical investigation. Mechanistically, MCS provides the obvious benefits of supporting systemic perfusion while reducing cardiac workload; risks include bleeding, thrombosis, hemolysis, limb ischemia, and other vascular complications.
• MCS should be weaned slowly using multiple clinical and hemodynamic parameters, including Swan Ganz catheter data.
• If unable to wean MCS due to insufficient myocardial recovery despite support over a prolonged period in the setting of adequate revascularization, additional options such as durable MCS, heart transplantation, or palliative care should be considered.

4.     What is the current evidence base for culprit-only vs. complete revascularization in AMI CS?

• The CULPRIT-SHOCK trial showed an increased 30-day and 1-year risk of a composite of all-cause mortality and need for renal replacement therapy in patients that underwent culprit and immediate non-culprit vessel revascularization in AMI CS.
• While there is no definitive data to support complete revascularization in AMI CS, this strategy may be considered in patients with multiple possible culprit lesions or subtotal non-culprit lesions with reduced TIMI grade flow corresponding with wall motion abnormality and normal wall thickness suggestive of viable myocardium.

1. Tehrani BN, Truesdell AG, Psotka MA, et al. A Standardized and Comprehensive Approach to the Management of Cardiogenic Shock. JACC Hear Fail. 2020;8(11):879-891. doi:10.1016/j.jchf.2020.09.005
2. Kapur NK, Davila CD. Timing, timing, timing: the emerging concept of the ‘door to support’ time for cardiogenic shock. Eur Heart J. 2017;38(47):3532-3534. doi:10.1093/eurheartj/ehx406
3. Hochman JS, Sleeper LA, Webb JG, et al. Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock. N Engl J Med. 1999;341(9):625-634. doi:10.1056/NEJM199908263410901
4. Ibanez B, Halvorsen S, Roffi M, et al. Integrating the results of the CULPRIT-SHOCK trial in the 2017 ESC ST-elevation myocardial infarction guidelines: viewpoint of the task force. Eur Heart J. 2018;39(48):4239-4242. doi:10.1093/eurheartj/ehy294
5. Shah AH, Puri R, Kalra A. Management of cardiogenic shock complicating acute myocardial infarction: A review. Clin Cardiol. 2019;42(4):484-493. doi:10.1002/clc.23168
6. Basir MB, Kapur NK, Patel K, et al. Improved Outcomes Associated with the use of Shock Protocols: Updates from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv. 2019;93(7):ccd.28307. doi:10.1002/ccd.28307
7. Doll JA, Ohman EM, Patel MR, et al. A team-based approach to patients in cardiogenic shock. Catheter Cardiovasc Interv. 2016;88(3):424-433. doi:10.1002/ccd.26297
8. Thiele H, Ohman EM, de Waha-Thiele S, Zeymer U, Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019. Eur Heart J. 2019;40(32):2671-2683. doi:10.1093/eurheartj/ehz363
9. Thiele H, Akin I, Sandri M, et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017;377(25):2419-2432. http://www.nejm.org/doi/10.1056/NEJMoa1710261. Accessed April 10, 2021.
10. Van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement from the American Heart Association. Circulation. 2017;136(16):e232-e268. doi:10.1161/CIR.0000000000000525
11. Henry, Timothy D., et al. “Invasive Management of Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Scientific Statement from the American Heart Association.” Circulation, vol. 143, no. 15, 2021, doi: 10.1161/cir.0000000000000959.

Dr. Venu Menon earned his medical degree from Jawaharlal Institute of Postgraduate Medical Education and Research in Pondicherry, India. He completed his internship and residency in internal medicine at St. Luke’s-Roosevelt Hospital in New York, NY, where he served as a Chief Resident. He continued at St. Luke’s-Roosevelt for his Cardovascular fellowship. Dr. Menon is currently the Mehdi Razavi Endowed Chair and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine. He serves as the section head of clinical cardiology, fellowship program director, and director of the Cardiac intensive care unit at the Cleveland Clinic. He is the Chair of the AHA’s Acute Cardiac Care and General Cardiology Committee of the Council on Clinical Cardiology.

Dr. Priya Kothapalli completed her medical school at Temple University. She did her residency at Houston Methodist. She is currently the chief fellow and CardioNerds ambassador at University of Texas at Austin, and will soon become the institution’s first ever interventional cardiology fellow

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.

The following question refers to Section 6.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by Houston Methodist medicine resident Dr. Najah Khan, and then by expert faculty Dr. Jaideep Patel.

Dr. Patel recently graduated from Virginia Commonwealth University cardiology fellowship and is now a preventive cardiologist at the Johns Hopkins Hospital.

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.

A 60-year-old Black woman with a history of hypertension and heart failure with reduced ejection fraction (EF 40%) presents to clinic for follow-up. She is currently doing well with NYHA class II symptoms. She is taking carvedilol 25 mg BID, sacubitril/valsartan 97/103 mg BID, and spironolactone 25 mg daily, all of which have been well tolerated. In clinic, her BP is 125/80 mmHg, and her HR is 55 bpm. Routine labs are within normal limits including Cr of 1.0, K of 4.0, and HbA1c of 6.0. What is the most appropriate next step in her management?

A. No change in management
B. Reduce beta blocker
C. Add an SGLT2 inhibitor (dapagliflozin or empagliflozin)
D. Add vericiguat
E. Add hydralazine/isosorbide dinitrate

The correct answer is C – Add an SGLT2 inhibitor (dapagliflozin or empagliflozin)

For patients with symptomatic HFrEF, neurohormonal antagonists (ACEi, ARB, ARNI; BB; MRA) improve survival and reduce the risk of HF hospitalization. This patient is already on these agents. The addition of an SGLT2 inhibitor on top of neurohormonal blockade reduces the risk of CV death and worsening HF in patients with symptomatic HFrEF and is the next best step for this patient (Class I, LOE A).

Vericiguat may be considered in patients with symptomatic HFrEF with HF worsening despite already being on maximally tolerated neurohormonal blockade (Class IIb, LOE B), but first-line therapies should be started first.

Hydralazine/Isosorbide dinitrate should be considered in self-identified Black patients or people who have EF ≤ 35% or <45% with dilated LV with class III-IV symptoms despite maximally tolerated neurohormonal blockade (Class IIa, LOE B), but is not the next best step here.

She is tolerating the beta blocker without adverse effects so there is no reason to decrease the dosage.

Main Takeaway

In patients with symptomatic HFrEF (EF ≤ 40%), SGLT2 inhibitors are considered first line therapy in addition to ACE-I/ARB/ARNI, BB, and MRAs to reduce the risk of HF hospitalization and death. Importantly this is irrespective of presence of diabetes.

Guideline Location

Section 6.2, page 3295-3296

Figure 13 page 3278; recommendation table page 3279.

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The following question refers to Section 4.9 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by UCSD fellow Dr. Patrick Azcarate, and then by expert faculty Dr. Melissa Tracy.

Dr. Tracy is a preventive cardiologist, former Director of the Echocardiography Lab, Director of Cardiac Rehabilitation, and solid organ transplant cardiologist at Rush University.

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.

A 74-year-old man with a history of hypertension, chronic kidney disease, and gastroesophageal reflux presents with chest pain and is found to have an NSTEMI due to an obstructive lesion in the proximal LAD. One drug-eluting stent is placed, and he is started on dual antiplatelet therapy with aspirin and clopidogrel. He is concerned about the risk of bleeding from his gastrointestinal tract. What would you recommend to reduce his risk of bleeding?

A. Lansoprazole, a proton pump inhibitor
B. Famotidine, a histamine-2 blocker
C. Calcium carbonate, an antacid
D. None, proton pump inhibitors are contraindicated.

The correct answer is A.

The ESC recommends that patients at high risk for GI bleeding who are receiving antiplatelet therapy take proton pump inhibitors (Class I, LOE A). High risk for bleeding includes patients who are age ≥65, history of peptic ulcer disease, Helicobacter pylori infection, dyspepsia or GERD symptoms, chronic renal failure, diabetes mellitus, and concomitant use of other antiplatelet agents, anticoagulants, nonsteroidal anti-inflammatory drugs, or steroids.

Coadministration of proton pump inhibitors that specifically inhibit CYP2C19 (omeprazole or esomeprazole) may reduce the pharmacodynamic response to clopidogrel. Although this interaction has not been shown to affect the risk of ischemic events, coadministration of omeprazole or esomeprazole with clopidogrel is not recommended.

Main Takeaway

In patients with high gastrointestinal bleeding risk who are receiving antiplatelet therapy, proton pump inhibitors are recommended. Omeprazole and esomeprazole may reduce the efficacy of clopidogrel and should not be used concomitantly with clopidogrel.

Guideline Location

Section 4.9.3, Page 3291

Figure 13 page 3278; recommendation table page 3279.

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The following question refers to Section 4.6 and Figure 13 of the 2021 ESC CV Prevention Guidelines. The question is asked by student doctor Shivani Reddy, answered first by NP Carol Patrick, 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.

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.

True or False: For patients with established ASCVD, secondary prevention entails adding a PCSK9 inhibitor if goal LDL is not met on maximum tolerated doses of a statin and ezetimibe.

The correct answer is True.

The ultimate on-treatment LDL-C goal of <55 mg/dL (<1.4 mmol/L) and a reduction of at least ≥50% from baseline should be considered for primary prevention of persons <70 years of age at very high risk (Class IIa) and in those with established ASCVD (Class I).

It is recommended that a high-intensity statin is prescribed up to the highest tolerated dose to reach these LDL-C goals (Class I).

The combination of statin with ezetimibe brings a benefit that is in line with meta-analyses showing that LDL-C reduction has benefits independent of the approach used.  The beneficial effect of ezetimibe is also supported by genetic studies. Together, these data support the position that ezetimibe should be considered as second-line therapy, either on top of statins when the therapeutic goal is not achieved (Class I), or when a statin cannot be prescribed (Class IIa).

PCSK9 inhibitors (monoclonal antibodies to PCSK9) decrease LDL-C by up to 60%, either as monotherapy or in addition to the maximum tolerated dose of statin and/or other lipid-lowering therapies, such as ezetimibe. Their efficacy appears to be largely independent of background therapy. Among patients in whom statins cannot be prescribed, PCSK9 inhibition reduced LDL-C levels when administered in combination with ezetimibe. Both alirocumab and evolocumab effectively lower LDL-C levels in patients who are at high or very high CVD risk, including those with DM, with a large reduction in future ASCVD events.

Therefore, for those who do not meet LDL-C goals with maximally tolerated doses of both a statin and ezetimibe, combination therapy including a PCSK9 inhibitor may be considered for primary prevention of patients at very high risk but without familial hypercholesterolemia (Class IIa) and is recommended for secondary prevention for those with established ASCVD (Class I). In addition, for very-high-risk FH patients (that is, with ASCVD or with another major risk factor) who do not achieve their goals on a maximum tolerated dose of a statin and ezetimibe, combination therapy including a PCSK9 inhibitor is recommended (Class I).

Main Takeaway

Statins, ezetimibe, and PCSK9 inhibitors should be used in a stepwise approach to achieve target lipid lowering goals in accordance with their risk profile.

Guideline Location

Page 3279, Sections 4.6.3.1.4, 4.6.3.1.5

Figure 13 page 3278; recommendation table page 3279.

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The following question refers to Section 4.3 of the 2021 ESC CV Prevention Guidelines. The question is asked by CardioNerds Academy Intern Dr. Maryam Barkhordarian, answered first by pharmacy resident Dr. Anushka Tandon and then by expert faculty Dr. Kim Williams.

Dr. Williams is Chief of the Division of Cardiology and is Professor of Medicine and Cardiology at Rush University Medical Center. He has served as President of ASNC, Chairman of the Board of the Association of Black Cardiologists (ABC, 2008-2010), and President of the American College of Cardiology (ACC, 2015-2016).

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.

Your patient mentions that she drinks “several” cups of coffee during the day. She also describes having a soda daily with lunch and occasionally a glass of wine with dinner. Which of the following recommendations is appropriate?

 A. Coffee consumption is not harmful and may even be beneficial, regardless of the number of drinks per day.
B. Drinking two glasses of wine/day is safe from a cardiovascular prevention standpoint.
C. Soft drinks (and other sugar-sweetened beverages) must be discouraged.
D. None of the above

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The correct answer is C.  Soft drinks (and other sugar-sweetened beverages) must be discouraged.

Sugar-sweetened beverages have been associated with a higher risk of CAD and all-cause mortality. The ESC guidelines give a class I recommendation for restriction of free sugar consumption (in particular sugar-sweetened beverages) to a maximum of 10% of energy intake. This is a class IIa recommendation in the ACC/AHA guidelines.

Choice A is incorrect because: the consumption of nine or more drinks a day of non-filtered coffee (such as boiled, Greek, and Turkish coffee and some espresso coffees) may be associated with an up to 25% increased risk of ASCVD mortality. Moderate coffee consumption (3-4 cups per day) is probably not harmful, and perhaps even moderately beneficial.

Choice B is incorrect: It is a class I recommendation to restrict alcohol consumption to a maximum of 100 g per week. The standard drink in the US contains 14 g of alcohol, so 100 mg of alcohol translate to:

o   84 ounces of beer (5% alcohol)

o   Or 56 – 63 ounces of malt liquor (75% alcohol) or

o   Or 35 ounces of wine (12% alcohol) or ONE 5 fl oz glass of wine/day.

o   Or 31.5 ounces of distilled spirits (40% alcohol).

The ACC/AHA guidelines recommended limiting alcohol consumption only for the management of hypertension to: ≤2 drinks daily for men and: ≤1 drink daily for women.

Main Takeaway

The main takeaway: ASCVD risk reduction can be achieved by restricting sugar-sweetened beverages to a maximum of 10% of energy intake.

Guideline Location

Section 4.3.2, Page 3271

CardioNerds Decipher the Guidelines – 2021 ESC Prevention Series
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