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Echocardiographic Assessment of PTTM patients in the ED
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This entry is adapted from the peer-reviewed paper 10.3390/diagnostics12020259

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease that obstructs pulmonary vessels, leading to pulmonary hypertension (PH) and right-sided heart failure causing rapid progressive dyspnea in patients with cancer. 

pulmonary tumor thrombotic microangiopathy: echocardiography right heart failure pulmonary hypertension malignancy

1. Introduction

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and fatal disease that obstructs pulmonary vessels, leading to pulmonary hypertension (PH) and right-sided heart failure [1] that causes rapid progressive dyspnea in patients with cancer. PTTM is caused by tumor cell microemboli, leading to progressive vascular occlusion with obstructive fibro-intimal remodeling in tiny pulmonary arteries, veins, and lymphatic systems [2]. A confirmed diagnosis of PTTM requires cytological examination of the aspirate from a wedge-shaped pulmonary artery catheter and lung biopsy [2][3][4]. However, when a patient with PTTM presents to the emergency department (ED) with shortness of breath, exacerbation advances quickly and often leads to death, making ante-mortem diagnosis and treatment challenging. As the number of patients with PTTM increases along with increase in the number of patients with cancer, it is essential to recognize the clinical characteristics and echocardiographic findings of PTTM to initiate appropriate therapy in the ED.
Point-of-care ultrasound (POCUS) has been widely used worldwide as a valuable tool for rapid bedside evaluation and treatment of patients with dyspnea [5][6]. Adding POCUS to the usual diagnostic approaches that rely on radiological and laboratory results has been shown to improve diagnostic accuracy and reduce diagnostic time through bedside evaluations of thoracic lesions and heart function [7][8]. However, although PH and right-sided heart failure are well-known features of the clinical course of PTTM, no studies have reported detailed echocardiographic findings concerning patients with PTTM [9].

2. Baseline Characteristics and Clinical Manifestations

The median age of the nine patients with PTTM was 53 years, and eight patients were female. Within a few days, all patients experienced severe and rapidly worsening dyspnea, and most had a high oxygen demand of >5 L/min via a facial mask. Among the seven patients with cancer, four had breast cancer, two had stomach cancer, and one had bladder cancer. Two patients were suspected of having cancer in the ED, but pathological confirmation was not possible due to a rapid deterioration in their clinical symptoms. After a clinical diagnosis of PTTM in the ED, two patients almost immediately underwent chemotherapy within 48 h, and they are currently alive and undergoing treatment. The remaining patients died within 3 days of hospital admission from the ED (Table 1).
Table 1. Demographic characteristics and clinical findings concerning patients with PTTM in the ED.
Table
Case Age (year) Sex PH History Malignancy Diagnosis before ED Dyspnea Exacerbation (days) Oxygen Needs (/min) D-Dimer (μg/mL) NT-Pro BNP (pg/mL) Primary Malignancy ChemoTx. Initiation Time from ED Death Time to Death (days)
1 40 F − + 3 FM 5L 3.41 3664 Breast Ca. − + 2
2 47 F − − 10 FM 15L 4.28 8153 Ovarian Ca. − + 1
3 59 F − + 7 HFNC 25.09 4253 Breast Ca. − + 3
4 41 F − − 3 NC 4L 60.00 4273 MUO − + 3
5 59 F − + 1 NC 3L 6.64 9130 Breast Ca. 24 h − −
6 43 F − + 2 FM 15L 16.52 5311 Gastric Ca. 48 h − −
7 54 F − + 1 NC 5L 6.18 1728 Breast Ca. − + N/A
8 73 F − + 2 FM 8L 28.11 21,925 Gastric Ca. − + 1
9 53 M − + 14 FM 5L 17.98 1520 Bladder Ca. − + 3

3. Laboratory Tests, Plain Chest Radiography, and CT Findings

Cardiac enzyme levels concerning troponin T and D-dimer were both high in all nine patients. There were no specific findings other than right-axis deviation on the electrocardiogram. The median interquartile (IQR) D-dimer and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels were particularly high at 16.52 (6.18–25.09) μg/mL and 4237 (3664–8153) pg/mL, respectively (Table 1). Plain chest radiography findings indicated that 50% of the patients had cardiomegaly and enlargement of the pulmonary trunk. Abnormalities of the lung, such as GGOs or interstitial thickening, were observed in only two patients, with most patients showing no new pulmonary lesions. On chest CT, specific findings of PTTM, such as a vascular tree-in-bud sign and centrilobular GGNs were identified in five and eight patients, respectively. In particular, all patients had an RV: LV ratio > 1, indicating RV dilation. Nonspecific findings included peripheral wedge GGOs, interstitial thickening, and consolidation. Except for one patient with a minor subsegmental PTE, all patients were grossly clear of PTE (Table 2, Figure 2).
Diagnostics 12 00259 g002 550
Figure 2. Chest CT findings concerning patients with PTTM. A 73-year-old woman with advanced gastric cancer (Case 8). (A) Bilateral lung CT scan results showing disseminated centrilobular GGNs (yellow arrows), (B) in which occasional vascular trees-in-bud signs (yellow squares) are noted. (C) Right and left ventricle (RV and LV) diameters are 4.1 cm and 1.8 cm, respectively, and the RV: LV ratio is 2:3, indicating that RV dysfunction, despite pulmonary arterial thromboembolism is not being depicted. Abbreviations: CT, computed tomography; GGNs, ground-glass nodules; LV, left ventricle; PTTM, pulmonary tumor thrombotic microangiopathy; RV, right ventricle.
Table 2. Radiologic features concerning patients with PTTM.
Table
Case Plain Radiography Computed Tomography
Cardiomegaly Pulmonary Trunk Enlargement Abnormal Findings RV Inner Cavity (cm) LV Inner Cavity (cm) RV: LV Ratio PTE Vascular Tree-in-Bud Sign Centri- Lobular GGNs
<3 mm		 Peripheral Wedge GGOs Interstitial Thickening Consolidation
1 − + − 4.1 3.4 1.2 − − Diffuse − − −
2 + + − 4.3 2.8 1.5 − − - − − −
3 − − − 3.5 1.9 1.8 − − Several random + − −
4 + − − 3.2 2.0 1.6 + + Diffuse − + −
5 + − − 3.3 2.7 1.2 − + Diffuse + − −
6 + + GGOs, pleural effusion 4.4 3.0 1.5 − + Several segmental + − +
7 − + − 3.6 3.1 1.2 − − Diffuse + − −
8 − + Interstitial thickening 4.1 1.8 2.3 − + Diffuse + + −
9 − − − 3.7 1.6 2.3 − + Diffuse − − −

4. Echocardiography Findings

Echocardiography was performed by emergency physicians for all nine patients, and the characteristic findings are described in Table 3 and Figure 3. All patients showed moderate-to-severe RV dilatation with D-shaped LV on echocardiography. The base and mid-RV median sizes (IQR) were 4.2 (4.2–4.5) cm and 3.4 (3.1–3.7) cm, respectively. The median TR Vmax (IQR) was 3.8 (3.5–3.8) m/s, and the median RVSP was 63 (58–79) mmHg, indicating severe PH. The median value of TAPSE (n = 7) was 15 (11–17) mm, showing a decrease in RV systolic function, with one patient having a normal value of 21 mm. The values of S’ (n = 4) ranged from 7.7 to 11.9 cm/s. Notably, five patients showed McConnell’s signs of RV dysfunction with a regional pattern of akinesia of the medial free wall, but normal motion at the apex. However, the LV size was normal in all patients, and the LV ejection fraction did not decrease significantly, ranging from 56% to 67%. The e/e′ values for LV diastolic dysfunction in four patients were within the normal range (5.7–8.9).
Diagnostics 12 00259 g003 550
Figure 3. Specific echocardiography features concerning patients with PTTM. A 40-year-old woman with breast cancer (Case 1). (A) Echocardiography results indicate RV dilatation with a D-shaped LV (mid/basal RV size: 29/40 mm). (B) TAPSE and S’ are 11.4 mm and 7.4 cm/s, respectively, indicating a decrease in RV systolic function. (C) The TR Vmax is 3.56 m/s, indicating PH. (D) McConnell’s sign, which is an akinesia of the RV mid-free wall except for the apex (red arrow), is observed. Abbreviations: A4C, apical 4 chamber; PLAX, parasternal long axis; PSAX, parasternal short-axis view; PTTM, pulmonary tumor thrombotic microangiopathy; RV, right ventricle; RVSP, right ventricular systolic pressure; S’, lateral tricuspid annulus peak systolic velocity on tissue Doppler imaging; TAPSE, tricuspid annular plane systolic excursion; TR V max, tricuspid regurgitation maximum velocity.
Table 3. Echocardiographic findings concerning patients with PTTM.
Table
Case LV RV
Size EF * (%) Diastolic Function
(e/e′)		 RV Dilatation † Size (Base/Mid) (mm) D-Shape TAPSE (mm) S′ (cm/s) TR Vmax (m/s) RVSP (mmHg) McConnell’s Sign
1 Normal 62 7.1 Moderate 40/29 + 11.4 7.7 3.56 56 +
2 Normal Normal N/A Severe N/A + 8 N/A 3.6 60 −
3 Normal 67 N/A Severe 42/33 + 21.1 11.9 4.5 87 +
4 Normal 63 N/A Severe 42/39 + 16.4 N/A 3.7 72 +
5 Normal 57 N/A Severe 50/34 + 17 11.3 3.82 64 +
6 Normal 58 5.7 Moderate 44/37 + 15.3 N/A 3.43 62 +
7 Normal 56 8.9 Moderate 45/37 + N/A N/A 3.49 54 −
8 Normal Normal N/A Severe N/A + N/A N/A N/A N/A −
9 Normal 56 5.8 Moderate 42/31 + 13.5 10.6 4.91 93 −

References

  1. Godbole, R.H.; Saggar, R.; Kamangar, N. Pulmonary tumor thrombotic microangiopathy: A systematic review. Pulm. Circ. 2019, 9, 1–13.
  2. Price, L.C.; Wells, A.U.; Wort, S.J. Pulmonary tumour thrombotic microangiopathy. Curr. Opin. Pulm. Med. 2016, 22, 421–428.
  3. Mitsui, Y.; Yagi, M.; Muraki, S.; Matsuura, T.; Bando, Y.; Fujimoto, S.; Kitamura, S.; Okamoto, K.; Muguruma, N.; Sata, M.; et al. Pulmonary Tumor Thrombotic Microangiopathy Due to Gastric Cancer Diagnosed Antemortem by a Cytological Examination of Aspirated Pulmonary Artery Blood. Intern. Med. 2021, 8313–8321.
  4. Takada, N.; Nishida, H.; Kondo, Y.; Oyama, Y.; Kusaba, T.; Kadowaki, H.; Hirakawa, K.; Iwao, S.; Kiyooka, S.; Daa, T. Pulmonary wedge aspiration cytology for the rapid diagnosis of pulmonary tumor thrombotic microangiopathy: A case report. Diagn. Cytopathol. 2021, 49, E277–E280.
  5. Lee, L.; DeCara, J.M. Point-of-Care Ultrasound. Curr. Cardiol. Rep. 2020, 22, 1–10.
  6. Ha, Y.-R.; Toh, H.-C. Clinically integrated multi-organ point-of-care ultrasound for undifferentiated respiratory difficulty, chest pain, or shock: A critical analytic review. J. Intensiv. Care 2016, 4, 1–19.
  7. Marbach, J.A.; Almufleh, A.; Di Santo, P.; Simard, T.; Jung, R.; Diemer, G.; West, F.M.; Millington, S.J.; Mathew, R.; Le May, M.R.; et al. A Shifting Paradigm: The Role of Focused Cardiac Ultrasound in Bedside Patient Assessment. Chest 2020, 158, 2107–2118.
  8. Pirozzi, C.; Numis, F.G.; Pagano, A.; Melillo, P.; Copetti, R.; Schiraldi, F. Immediate versus delayed integrated point-of-care-ultrasonography to manage acute dyspnea in the emergency department. Crit. Ultrasound J. 2014, 6, 5.
  9. Von Herbay, A.; Illes, A.; Waldherr, R.; Otto, H.F. Pulmonary tumor thrombotic microangiopathy with pulmonary hypertension. Cancer 1990, 66, 587–592.
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Hee Yoon
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