Nitroprusside challenge: goals and interpretation

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

Show notes – Challenging Cases – Nuances in Pulmonary Hypertension Management with Dr. Ryan Tedford

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.

References – Challenging Cases – Nuances in Pulmonary Hypertension Management with Dr. Ryan Tedford

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.

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