Becton, Dickinson and Company · NYSE:BDX
Becton, Dickinson and — Investor Presentation (November 2023)
76 slides from Becton, Dickinson and's investor presentation, November 2023
Slide 1: Pulmonary Hypertension: A Case of a Congenital Conundrum
PULMONARY HYPERTENSION: A CASE OF A CONGENITAL CONUNDRUM Amy Cecchini, DO, PGY5 EVMS Pulmonary/Critical Care Fellow
Slide 2: Hello, I have a new pulmonary consult
“Hello, I have a new pulmonary consult:” Reason for consult: A 75-year old male with hypoxia of unclear cause Chief complaint: presented to ED for abdominal pain, constipation, mild dyspnea
Slide 3: Past Medical History
Past Medical History: End-stage renal disease on peritoneal dialysis Renal cell carcinoma s/- L complete and R partial nephrectomy History of aspiration pneumonia/ARDS with septic shock and prolonged ICU admission Hypertension
Slide 4: In the ED: Physical Exam
In the ED: Physical Exam Vitals: BP: 119/78 - HR: 105 bpm - Temp: 97.6 F - RR: 16 - O2 sat: 98% on 4L - BMI: 22.5 - Weight 176lbs Exam: General: NAD, well-nourished CV: Regular rhythm, slightly tachycardic Resp: normal effort without wheezing, rales Abdomen: soft, nontender, PD catheter
Slide 5: In the ED: Laboratory Values
In the ED: Laboratory Values CBC: Lactate 2.9-3.5 mmol/L Hb: 9.0 g/dL NT-Pro BNP: >70,000 pg/mL WBC: 14.6 K/uL High-sensitivity troponin: 200 ng/L Plt: 340 K/uL ABG: 7.519/37.2/107/30.3 (on non- rebreather mask) CMP: Cr: 10.7 mg/dL K 3.9 mmol/L Na: 143 mmol/L CO2: 29 mmol/L
Slide 6: In the ED: Further Workup
In the ED: Further Workup CT Abd/Pelvis: Mild bladder wall thickening, moderate ascites PD Fluid: Cell count: WBC 18,090 Cultures grew Klebsiella Admitted for IV antibiotic treatment of sepsis secondary to peritonitis
Slide 7: What about the dyspnea and hypoxia?
What about the dyspnea and hypoxia? Vague, ongoing for ”many years,” worse with exertion Increased over the past 2 days, with mild clear to white sputum production
Slide 8: Echocardiogram
Echocardiogram: LV EF: 55%, indeterminate diastolic dysfunction Asymmetrical LVH with apical and septal dyssynchrony. Right ventricular chamber is enlarged. Severe pulmonary hypertension- PASP 105 mmHg. Bubble study negative for shunt.
Slide 9: Question
Question: What is your diagnostic approach for workup in dialysis patients with elevated pulmonary pressures? What workup would you like to see next?
Slide 10: S| E> SENTARA
S| E> SENTARA School
Slide 11: Slide 11
Slide 12: Slide 12
Slide 13: Slide 13
Slide 14: CTA Chest Interpretation
CTA Chest Interpretation: No evidence of PE No identified right pulmonary artery, presumed congenital. Marked hypoplasia of the right lung with volume loss and rightward shift of the heart and mediastinum Chronic changes on right, bilateral ground glass opacities Mosaic attenuation of L lu
Slide 15: Pulmonary Perfusion Scan, Quantitative with Split Function Calculation
Pulmonary Perfusion Scan, Quantitative with Split Function Calculation Asymmetric pulmonary perfusion with essentially complete absence of perfusion to the severely dysplastic right lung Based on calculated split function, the left lung receives 100% and the right lung receives 0% of total pulmo
Slide 16: Quantitative VQ Scan
Quantitative VQ Scan:
Slide 17: PFTs
PFTs: Interpretation: • Variable extrathoracic obstruction. • No obstruction or restriction. Overinflation and air trapping. • Moderately reduced DLCO.
Slide 18: Six Minute Walk Test
Six Minute Walk Test: Adequate O2 saturations at rest Required 1L supplemental O2 to maintain O2 saturations above 88% Ambulated 56% of predicted walk distance Patient declined home O2
Slide 19: Serologies
Serologies: GENERAL SEROLOGY &© Citrulline Antibody Joz423 <05 ]<os RHEUMATOID FACTOR QUANTIT.... 07/14/23 <20 ]<20 HIV 1/0/2 Antigen/Antibody wiReflex | 07/14/23 Non Reactive | Non Reactive HIV Interpretation ]oz/423 HtVv-1 antig... | HIVv-1 antigen ... HBS AB Qnt Joz023 22.88 * | 22.88 * ANTLNUCLE
Slide 20: Summary thus far
Summary thus far: Patient with pulmonary hypertension of likely multifactorial causes: Absent RPA Diastolic dysfunction ESRD on peritoneal dialysis Chronic hypoxia
Slide 21: Updated classification and management of pulmonary hypertension
Nef HM, Möllmann H, Hamm C, et al Updated classification and management of pulmonary hypertension Heart 2010;96:552-559.
Slide 22: Question
Question: What workup would you like to obtain next? Unfortunately, the patient has not followed up for right heart catheterization as of yet.
Slide 23: Next Steps: How to Treat?
Next Steps: How to Treat? ESRD on PD: optimize volume status for euvolemia Absent RPA with fibrotic R lung and overdistention of L lung: added bronchodilators to improve airflow Chronic hypoxia: supplemental O2 Possible/indeterminate diastolic dysfunction: optimize volume status and maintain
Slide 24: Mechanism of PH in Absent RPA
Mechanism of PH in Absent RPA: Blood flow is directed away from the absent R PA to the L PA. Increased blood flow in the L PA causes shear stress on the endothelium. This causes the release of vasoconstrictors such as endothelin. Chronic vasoconstriction of the pulmonary vasculature can lead
Slide 25: Question
Question: If this is precapillary pulmonary hypertension, what would your preferred treatment choice be?
Slide 26: Question
Question: With his heart failure, what would your concern be regarding treatment with pulmonary vasodilators?
Slide 27: Literature Review
Literature Review: Unilateral absence of pulmonary artery (UAPA) is a rare congenital abnormally caused by the failure of the sixth aortic arch to connect with the pulmonary trunk during the embryologic development. About 350 cases were reported in the world literature between 1868 and 2010.
Slide 28: Literature Review
Literature Review: Data is limited as this is a rare diagnosis One retrospective review of cases of 108 patients with UAPA showed that 44% of patients had PH No formal guidelines on management Suggested yearly screening echoes in these patients for development of PH
Slide 29: Literature Review
Literature Review: Another analysis of 65 patients with UAPA suggested that PH treatment with vasodilator therapy may help significantly Patients treated with pulmonary vasodilators reported improvement in dyspnea and WHO functional class in 50% of patients with congenital PA absence and PH
Slide 30: References
References: Wang P, Yuan L, Shi J, Xu Z. Isolated unilateral absence of pulmonary artery in adulthood: a clinical analysis of 65 cases from a case series and systematic review. Journal of Thoracic Disease. 2017;9(12):4988-4996. David W. Reading & Umesh Oza (2012) Unilateral Absence of a Pulmonar
Slide 31: Pulmonary Hypertension and the Possible Interactions with Cancer Treatment, Infection Treatment, and Anesthesia
Pu lm on a ry Hyperten s ion a n d th e Pos s ible In tera ction s w ith Ca n cer Trea tm en t, In fection Trea tm en t, a n d An es th es ia Kyle Adm ire, DO Mich a el Eggert, MD, FCCP Ma tth ew Bern en s , MD Ea s tern Virgin ia Medica l Sch ool, Depa rtm en t of Pu lm on a ry a n d Critica l Ca r
Slide 32: Our Patient
Our Patient 53 year old female Medications: PMH: ● Azathioprine ● Methotrexate ● Sjogren’s Disease ● Mycophenolate ● Dermatomyositis ● Prednisone ● Obesity (BMI >40) ● Pulmonary Hypertension ★ Inhaled Treprostinil ○ Groups 1 & 3 ★ Oral Sildenafil
Slide 33: CT Scan obtained for monitoring
CT Scan obtained for monitoring ● New 11.14mm LUL Nodule ● No other obvious lesions ● PET only shows uptake in this area
Slide 34: How would you manage this nodule?
How would you manage this nodule?
Slide 35: RHC and Echo results on Tyvaso and Sildenafil
RHC and Echo results obtained shortly before PET, on Tyvaso and Sildenafil
Slide 36: LUL Nodule - Our Management
LUL Nodule - Our Management ● Deemed too high risk for biopsy or resection ● PET showed avidity at this site, but no evidence of metastatic disease ● Treated with empiric stereotactic radiation ○ Acceptable response was obtained
Slide 37: Our Patient - Continued
Our Patient - Continued ● Following completion of radiation therapy, she was noted to have a necrotic hard palate lesion
Slide 38: Slide 38
Slide 39: Outpatient Biopsy Results
Outpatient Biopsy Results ● Actinomyces ● Repeat Biopsy: ○ ESBL Klebsiella ○ VR Enterococcus ○ Candida ○ Aspergillus
Slide 40: Next Steps
Next Steps: ● Planned treatment with daptomycin, meropenem, voriconazole ○ Required modification of her PH regimen ● Patient elected to pursue surgical debridement and partial maxillectomy with PEG tube placement
Slide 41: Would you change this patient's PH Regimen prior to the OR?
Would you change this patient’s PH Regimen prior to the OR?
Slide 42: Medication Interaction: Sildenafil and Voriconazole
Medication Interaction: Sildenafil and Voriconazole ● Sildenafil is metabolized by CYP3A4 ● Voriconazole inhibits CYP3A4 ● Toxicity: ○ Headaches ○ Hypotension ○ Heart failure
Slide 43: Pre-Surgical RHC
RESULTS: 9.5 ng/kg/min IV Remodulin, Tyvaso 8 inhalations 4 times daily RA 4 mmHg. RV 45/5 mmHg with an end-diastolic pressure of 6 mmHg PA 46/23 mmHg with a mean pressure of 31 mmHg PCWP 9 mmHg. TPG 22 mmHg. PA sat 61%. Aortic sat 100% TD CO 5.13 Limin TD Cl 2.80 Limin/m2 TD PVR 4.29 WU. Fick CO 5.
Slide 44: How would you manage this patient's induction and airway?
How would you manage this patient’s induction and airway?
Slide 45: Our Management
Our Management ● Prior to surgery, PAPs remained in the 40s/20s on IV treprostinil ● Low dose epinephrine started in the OR before induction for inotropy ● General anesthesia ○ Induced with etomidate ○ 6.5 intraoral ETT placed ● Extensive debridement by ENT and PEG tube placement by general surgery
Slide 46: Induction Agents in Patients with PH
Induction Agents in Patients with PH ● Etomidate ○ Drug of choice due to its low effect on SVR and PVR ○ Combination with synthetic opioids improves smoothness of induction ● Propofol ○ Avoid due to propensity for hypotension and myocardial depression ● Emerging evidence for Ketamine ○ Has the poten
Slide 47: Anesthesia Factors
> sEnNTARA Tastern Virginia |hiedical Selo) Anesthesia Factors Positive pressure Induction Medications cl cll Mh i-| Figure 3. Mechanisms of hemodynamic decompensation during the induction of anesthesia. IV, interventricular; LV, left ventricle; PVR, pulmonary vascular resistance; RV, right ventricl
Slide 48: Healed surgical site following extubation
Healed surgical site following extubation
Slide 49: Cytology Report
Cytology Report ● CD20+, CD30+ Diffuse Large B-Cell Lymphoma ○ Standard of care is R-CHOP ○ Our patient received R-CEOP
Slide 50: Antineoplastics in PH Patients
Antineoplastics in PH Patients ● Cardiotoxicity ● Drug-Induced PH ○ Anthracyclines ○ Cyclophosphamide ○ Platins ○ Dasatinib ○ Trastuzumab ○ Vincristine ● Pulmonary Parenchymal Disease ○ Bleomycin
Slide 51: Pre and Post R-CEOP
Pre and Post R-CEOP
Slide 52: A Recurrent Finding
A Recurrent Finding ● Left Upper Lobe again showed suspicious area of uptake in essentially the same location as her previous presumed cancer
Slide 53: CT-Guided Biopsy
CT-Guided Biopsy ● Keratinized squamous cell carcinoma ○ 15% Tumor Proportion Score (TPS) ● Deemed prohibitive risk for surgical resection ● Currently being managed with stereotactic radiation
Slide 54: Case Summary
Case Summary ❖ Patient on high-dose immunosuppressants with no ability to decrease dose per Rheumatology ❖ Developed LUL nodule (presumed cancer) - treated with radiation ❖ Developed DLBCL with superimposed polymicrobial infection ❖ LUL Squamous Cell Carcinoma (?Recurrence)
Slide 55: Should we be more concerned about malignancies among PH patients?
Should we be more concerned about malignancies among PH patients?
Slide 56: Case Conclusions
Case Conclusions ❖ Occam’s Razor ➢ Immunosuppression led to loss of checkpoints ■ At least two separate neoplasms ■ One superinfected with rare and resistant bacteria and fungi ➢ Could this have been prevented by modifying her immunosuppressant regimen?
Slide 57: Why is this important?
S| SEN DARA Why i is this important? — Pulmonary hypertension (N=11,109) — No pulmonary hypertension (N=11,109) 25% 232 20% 18.5 log-rank p<0.001 Patients with cancer diagnosis rm a #
Slide 58: Association between pulmonary hypertension and incidence of cancer diagnoses
Association between pulmonary hypertension and the incidence of cancer diagnoses in patients followed in general practices in Germany (Cox regression models) by age and sex Cancer Incidence (cases per 100,000 Incidence (cases per 100,000 Hazard incidence per patient years) among patients patient yea
Slide 59: Cancer hazard ratios by site
Cancertotal Respiratory organs Skin Urinary tract Male genital organs (men) Digestive organs excl. liver Urinary tract Lymphoidand hematopoietic tissue Breast(women) Female genital organs (women) Lip, oral cavity and pharynx | il Pt Hazard Ratio (HR) + 1,30 (1,18-1.43); p<0,001 + 1,60 (1.14-2.25); p
Slide 60: Citations
Citations ● Caddigan S, Granlund B. Anesthesia for Patients With Pulmonary Hypertension or Right Heart Failure. [Updated 2023 Jan 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572071/ ● Gürdoğan M, Demir
Slide 61: Perioperative Management & Complications in PAH
Perioperative Management & Complications in PAH Sam Anderson, MD Michael Eggert, MD, FCCP Matthew Bernens, MD Sentara/EVMS Pulmonary & Critical Care
Slide 62: Case
Case 74 yo female PMH • PAH with Group 1 features out of proportion to II & III (on Tyvaso 9 inh qid, sildenafil 20 mg tid) • Chronic hypoxemic respiratory failure (3-4 L HOT) • Moderate COPD • Emphysema • 50 pack year smoking history • Obesity (BMI=33) • OSA (not on CPAP) • Pulmonary asbestosis • H
Slide 63: Background hemodynamic data
Background hemodynamic data 5/10/23: PH initially discovered on ECHO w/ eRVSP = 92, FAC=15% 7/10/23: Right Heart Catheterization with 800 ml fluid challenge • RAP= 4 Post fluid challenge • mPAP= 42 • mPAP= 54 • PCWP= 10 • PCWP= 16 • CO (Fick) = 5.89 • CO (Fick) = 3.16 • CI (Fick) = 2.89 • CI (Fick)
Slide 64: Initial Presentation to OSH
Initial Presentation to OSH (10/12) • Nausea & Vomiting x2 days along with lower abd pain • BP=102/70, HR=88, O2 sat=96% (home O2) • Labs w/ WBC= 13.6k, BUN/Cr = 56/4.1 (bsl Cr ~2)
Slide 65: Timeline of events
Timeline of events • CT abd/pelvis: Findings consistent with SBO with transition point around area of distal jejunum • NPO w/ NGT for decompression, significant gastric volume losses w/ worsening AKI • 10/14: PPN started for nutrition • 10/16: Condition not improving, transferred to Sentara Heart Ho
Slide 66: ECHO (10/15)
ECHO (10/15) • Ef= 60%, indeterminate diastolic dysfunction • TAPSE= 1.8 cm, TAPSV = 19.5 cm/s, FAC =45% • Normal RV dimension • Flattening of septum in systole consistent with RV pressure overload • Unable to estimate PASP due to inadequate TR doppler waveforms
Slide 67: How would you optimize this patient for surgical intervention?
How would you optimize this patient for surgical intervention? How concerned are you about the surgical risk?
Slide 68: Timeline of events continued
Timeline of events continued 10/16: Transfer to Sentara Heart Hospital with severe pre-renal AKI (BUN=138 / Cr= 8.8). Started on TPN along with IVF to match volume of gastric losses 10/17: Small bowel series with gastrografin - confirms SBO – plan for surgery 10/18: Pt transitioned from tyvaso to IV
Slide 69: Intraoperative Events
Intraoperative Events • Started case on remodulin @11.7 ng/kg/min & vasopressin @ 0.03 U/min • MAP low 100's, mPAP mid 40's at start • Maintenance anesthetic with isoflurane • MAP dropped to low 70's – epinephrine started at 3 mcg/min, levophed started @5 mcg/min shortly thereafter)
Slide 70: Intraoperative events cont
Intraoperative events cont • Pt given esmolol 100 mg bolus due to tachycardia, decreased MAP response • Pt given phenylephrine afterwards • mPAP rises into 50's with drop in MAP into 50’s • Pt given 800 ml of additional IVF during procedure
Slide 71: How would you modify the initial anesthetic approach?
How would you modify the initial anesthetic approach? How would you rescue the patient after they had hemodynamic instability?
Slide 72: Intraoperative events cont.
Intraoperative events cont. • Epinephrine is titrated up with increase in MAP accompanied by decrease in mPAP. • Case completed - pt extubated and transferred back to ICU
Slide 73: Intraoperative Decompensation in PH
Intraoperative Decompensation in PH Most of the literature based on expert reviews & case reports Continuous fixed dose vasopressin infusion used preemptively during a case done with spinal anesthesia (4) Near fatal anesthesia induction during heart-lung transplant (5) - luxury of cardiopulmonar
Slide 74: Intraoperative Hemodynamic Goals
Intraoperative Hemodynamic Goals 1. Avoid systemic HoTN (maintain MAP >65) to ensure coronary perfusion & prevent RV ischemia. Goal MAP 20 mmHg above mPAP 2. Maintain NSR (Beta blockers poorly tolerated, amiodarone = drug of choice) 3. Avoid factors known to increase PVR (ie hypoxia, hypercarbia, ac
Slide 75: Summary
Summary Intraoperative monitoring: -PAC & TEE can be helpful in guiding management Maintain gradient between aorta and RV -NE & vasopressin: 1. Improve RCA perfusion 2. Reduce PVR/SVR ratio 3. Enhance RV performance Increase contractility -Epinephrine, Dobutamine RV afterload reduction with selectiv
Slide 76: References
References 1.Savale, L., Weatherald, J., Jaïs, X., Vuillard, C., Boucly, A., Jevnikar, M., ... & Humbert, M. (2017). Acute decompensated pulmonary hypertension. European Respiratory Review, 26(146). 2.Rajagopal, S., Ruetzler, K., Ghadimi, K., Horn, E. M., Kelava, M., Kudelko, K. T., ... & American H
Becton, Dickinson And Company — Investor Presentation (November 2023) on 6ix