Right-sided cardiogenic shock from acute pulmonary tumor thrombotic microangiopathy: a rare but deadly cardio-oncologic and metabolic emergency.

Abstract

Background: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal but treatable condition characterized by the rapid development of pulmonary hypertension (PH) in patients with possibly unknown adenocarcinoma. PTTM is mostly diagnosed post-mortem and considered a rare disease since its acute onset and misdiagnosis provides significant diagnostic and therapeutic challenges.

Methods: We conducted a retrospective analysis of patients who presented with unclear sudden cardiac death and acute right heart failure that had an incidental very recent or unknown malignant cancer, identified eight patients with PTTM and reported the results. Patients were considered from 2009 to 2024 and analyzed at Ulm University Heart Center, Germany with the aim to describe the fatal consequences of unknown acute PTTM with right heart failure and discuss diagnostic and therapeutic strategies.

Results: The median age was 47 years (41-84 years); gender was equally distributed. The latest median body mass index (BMI) was elevated with 28.4 kg/m² (25-36 kg/m²). All patients presented as an emergency and died in our hospital due to right heart failure caused by adenocarcinoma in various locations. Median high-sensitivity troponin T was elevated (42.5 (3-179, normal < 14) ng/L), median NT-pro-BNP (5375 (3100-14,000), normal < 800 for all age groups, in pg/mL), and d-dimer values (7.74 (1.1-21), normal < 0.5 for patients younger than 50 years and < 1 for all other age groups, in mg/FEU) were strongly elevated. Median HbA1c was slightly elevated 7.4% (normal < 6.5%). Median time from last hospital admission to death was 8 days (1-23 days). At admission, median systolic arterial pressure (sPAP) estimated by echocardiography was 65 (46-115) mmHg. Low NT-proBNP and sPAP values as well as pre-mortem adenocarcinoma diagnosis and (therewith associated) adenocarcinoma-type cancer of unknown primary (CUP) correlated best with longer survival in days (ρ and r-values: - 0.88, - 0.76, 0.58, 0.89 respectively). Initiation of specific therapy (chemotherapy or anticoagulation) was correlated with survival (ρ = 0.786, p = 0.02).

Conclusion: Our data suggest that the combination of elevated hsTnT, NT-proBNP, d-dimer, and HbA1c values in patients with unexplained acute right heart failure may indicate PTTM. Our findings also emphasize the diagnostic challenge posed by PTTM, and imply that targeted therapy, enabled by a timely diagnosis, may improve survival. Therefore, acute and fatal right heart failure in the adult in absence of coronary artery disease, pulmonary embolism, or any other apparent cause, especially in patients with uncontrolled metabolic syndrome, should prompt an urgent diagnostic work-up to rule out unknown cancer with treatable pulmonary tumor embolism, beginning with more extensive imaging (e.g., computed tomography (CT) and magnetic resonance tomography (MRI)), as well as laboratory diagnostics (e.g., tumor markers). In still inconclusive cases, lung biopsy and right heart catheterization should be considered eventually, if possible.