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An autopsy case of pulmonary arterial hypertension in an elderly patient with multimorbidity: a case report

An autopsy case of pulmonary arterial hypertension in an elderly patient with multimorbidity: a... CASE REPORT European Heart Journal - Case Reports (2022) 6(1), 1–6 https://doi.org/10.1093/ehjcr/ytab527 Heart failure An autopsy case of pulmonary arterial hypertension in an elderly patient with multimorbidity: a case report 1 1 2 1 Masashi Yokose , Takashi Tomoe , Takehiko Yamaguchi , and Takanori Yasu * 1 2 Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 632 Takatoku, Nikko, Tochigi 321-2593, Japan; and Department of Pathology, Dokkyo Medical University Nikko Medical Center, 632 Takatoku, Nikko, Tochigi 321-2593, Japan Received 4 June 2021; first decision 26 July 2021; accepted 22 December 2021; online publish-ahead-of-print 28 December 2021 Background There is an increasing number of elderly patients with pulmonary arterial hypertension (PAH), and their characteristics differ from those of young or middle-aged patients with this condition. ................................................................................................ ................................................................................................ ........................... Case summary A 73-year-old woman with a history of myocardial infarction and cardiovascular risk factors was admitted to the hospital with 2-week exertional dyspnoea. Her initial diagnosis was heart failure with preserved ejection fraction, but the symp- toms persisted despite receiving treatment with diuretics. Additional tests showed a significant decrease in diffusing cap- acity of carbon monoxide and findings suggestive of severe pulmonary hypertension (PH). Contrast-enhanced computed tomography of the chest, and pulmonary angiography, showed no narrowing or obstruction of the pulmonary arteries. Right heart catheterization revealed haemodynamic data implying pre-capillary PH. Her condition gradually deteriorated to World Health Organization functional class IV, and sequential combination therapy with tadalafil, macitentan, and selex- ipag was initiated with a PAH diagnosis; however, she died 1 month later. Pathological findings in autopsy were consistent with PAH, and some parts of the lungs revealed the presence of obstructive and interstitial lung disease. ................................................................................................ ................................................................................................ ........................... Discussion The majority of elderly patients with PAH might have multimorbidity. However, there is no specific treatment strategy. It is associated with diagnostic delay and worse prognosis; therefore, early suspicion and comprehensive tests, including right heart catheterization, are essential for better management. Keywords Case report Elderly patients Multimorbidity Pulmonary arterial hypertension • • • ................................................................................................ ................................................................................................ ........................... ESC Curriculum 9.6 Pulmonary hypertension 7.1 Haemodynamic instability Introduction Learning points The number of elderly patients with pulmonary arterial Pulmonary arterial hypertension (PAH) usually occurs in young adult 1,2 hypertension is increasing. They have multimorbidity and women. Diagnosis requires comprehensive investigation to identify worse prognosis compared with younger patients. . classification, severity, and aetiology. The current treatment strategy • . Pulmonaryarterial hypertensioninelderly patients might is based on disease severity; in severe cases, guidelines recommend deteriorate rapidly and its diagnosis is challenging; therefore, a specific drug therapy. Recently, the number of PAH in elderly high index of suspicion and early comprehensive tests are . patients has been increasing. Herein, we report an autopsy case of essential for better management. PAH in an elderly patient with multimorbidity. * Corresponding author. Tel: þ81(288)76-1515, Fax: þ81(288)76-1030, Email: tyasu@dokkyomed.ac.jp Handling Editor: Marta Cvijic Peer-reviewers: Sherif Mohammad Abd ElSamad; Mohammad El Tahlawi and Kyriakos Dimitriadis Compliance Editor: Brett Sydney Bernstein Supplementary Material Editor: Mariame Chakir V The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unre- stricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 2 M. Yokose et al. She lost 4 kg of weight within 4 days; however, her symptoms sus- Timeline tained. Arterial blood gas analysis while breathing ambient air . revealed a PaCO of 37 mmHg, PaO of 61.4 mmHg, SaO of 91.7%, 2 2 2 and alveolar-arterial oxygen gradient of 42.7 mmHg. The pulmonary Day 1 Patient was admitted with a history of 2-week exer- function test (PFT) showed a reduced forced vital capacity (FVC) of tional dyspnoea [World Health Organization func- 1.82 L (73.6% of predicted), reduced forced expiratory volume in 1 s tional classification (WHO-FC) II]. Tricuspid (FEV1) of 1.39 L (72.7% of predicted), mildly reduced FEV1/FVC of regurgitation pressure gradient (TRPG) was 54 76.3%, and markedly reduced diffusing capacity of carbon monoxide mmHg on trans-thoracic echocardiogram (TTE). (DLCO) of 5.76 mL/min/mmHg (30.4% of predicted). The 6 min Day 19 Follow-up TTE showed worsened TRPG (81 mmHg). walking test revealed reduced distance (88 m) and temporarily Day 36 Right heart catheterization revealed a mean pulmonary declined SpO (80%). arterial pressure of 58 mmHg, pulmonary vascular On the 19th day of admission, follow-up TTE showed a markedly resistance of 20 Wood units, and normal pulmonary hypokinetic and enlarged RV (40 mm), with decreased systolic func- arterial wedge pressure. . tion (tricuspid annular plane systolic excursion, 13.4 mm) and wors- Day 56 The patient experienced presyncope and significant . ened TRPG (81 mmHg; Figure 2C and D); estimated RAP remained hypotension during rehabilitation (WHO-FC IV). . 8 mmHg. Peak tricuspid regurgitation velocity was 4.5 m/s, consistent Day 60–90 The patient was treated with sequential triple combin- . with a high probability of pulmonary hypertension (PH). Contrast- ation therapy; however, the condition deteriorated. . enhanced chest CT detected no pulmonary embolism (Figure 3A and Day 94 The patient died. B). Right heart catheterization (RHC) revealed elevated mean pul- monary arterial pressure (58 mmHg) and pulmonary vascular resist- ance (20 Wood units), normal mean pulmonary arterial wedge . pressure (13 mmHg), and cardiac output/cardiac index (3.2 L/min and Case presentation . 2 . 1.9 L/min/m ), respectively. Vasoreactivity testing and fluid challenge . were not performed. There was no significant increase in oxygen sat- A 73-year-old obese woman (body mass index, 29.2 kg/m ) pre- uration between arterial and venous blood samples. Pulmonary angi- sented with 2-week exertional dyspnoea. Medical history included in- ferior myocardial infarction treated with percutaneous coronary ography demonstrated no narrowing or obstruction (Figure 3C and D). Coronary angiography was almost unremarkable except for 75% intervention in the proximal right coronary artery 17 years ago, dysli- stenosis in the distal left circumflex artery. She was diagnosed with pidaemia, hypertension, type 2 diabetes mellitus (DM), and stage 3 1,2 pre-capillary PH, and PAH was highly suspected. Additional tests chronic kidney disease (CKD); there was no relevant family history. for serum anti-human immunodeficiency virus antibody and autoanti- She had a 72-pack-year smoking history until age 56. Medications . included aspirin, carvedilol, rosuvastatin, losartan, nifedipine, isosor- . bodies associated with connective tissue diseases were all negative. . She was unable to undergo a ventilation/perfusion lung scan to ex- bide mononitrate, glimepiride, metformin, empagliflozin, and . clude chronic thrombo-embolic PH (CTEPH) due to presyncope, alogliptin. . progressive dyspnoea at rest, and significant hypotension. She was On physical examination, the patient appeared healthy: her heart diagnosed as World Health Organization functional class (WHO-FC) rate was 77 b.p.m.; blood pressure, 124/66 mmHg; respiratory rate, 18 breath per minute; and percutaneous oxygen saturation (SpO ), IV and treated with sequential combination therapy—including tada- 2 . 95% on 2 L of oxygen. Cardiopulmonary examinations were normal, lafil (20 mg/day, phosphodiesterase type 5 inhibitor) and macitentan (10 mg/day, endothelin receptor antagonist) after 2 weeks—which and laboratory data revealed elevated brain natriuretic peptide was ineffective (Figure 4 and Supplementary material online, Table (818 pg/mL). Electrocardiography showed sinus rhythm and inverted T waves in leads II, III, aVF, and V (Figure 1A). Chest radiography S1). The third medication—selexipag (oral prostacyclin receptor 1, 2 . revealed cardiomegaly, while chest computed tomography (CT) . agonist)—was added, its dose gradually increased; however, the without contrast showed bilateral pleural effusion and subpleural . patient’s respiratory status rapidly deteriorated on the 90th day of . admission. She refused intubation and died 4 days later. ground-glass opacity (GGO; Figure 1B and C). . An autopsy after 30 h (Figure 5A–D) revealed medial thickening Trans-thoracic echocardiography (TTE) revealed a normal sized, . and prominent luminal stenosis due to cellular intimal proliferation of hypertrophic (wall thickness, 12 mm) left ventricle (LV) with normal ejection fraction (65%), cardiac output (4.15 L/min), and cardiac index pulmonary arterioles, especially the smaller ones. Furthermore, there (2.28 L/min/m ); and signs of diastolic dysfunction (mitral E/A, 0.70; were emphysematous parenchymal changes, thickened alveolar mitral E velocity deceleration time, 285 ms; average E/ e, 18.9). The septa, and focal fibrosis, consistent with organizing pneumonia. Many lymphocytes and macrophages infiltrated alveoli. The enlarged heart right ventricle (RV) was hypertrophic and dilated, with a flattened interventricular septum and increased tricuspid regurgitation pres- exhibited focal fibrosis and myocardial fascicular arrangement of the sure gradient (TRPG, 54 mmHg; Figure 2A and B). The estimated right LV posterior wall, consistent with old myocardial infarction. The RV atrial pressure (RAP) was 8 mmHg, and the inter-arterial septum . wall was hypertrophic and mildly dilated. Focal amyloid deposits at remained intact. The patient was diagnosed with heart failure with . hyalinized islets of Langerhans in the pancreas, renal arteriosclerosis, preserved ejection fraction, and furosemide (10 mg/day) was and arteriolosclerosis, and scattered globally sclerotic glomeruli indi- administered. cated DM. An autopsy case of pulmonary arterial hypertension 3 Figure 1 Electrocardiography showed sinus rhythm and inverted T waves in leads II, III, aVF, and V (A). Chest computed tomography without 1, 2 contrast revealed bilateral pleural effusion and right-dominant subpleural ground-glass opacity from the apex (B)to base (C). Hjalmarsson et al. previously reported about 20% of elderly Discussion . patients >65 years old with idiopathic PAH have at least four comor- Currently, there are only a few case reports which confirmed rapidly bidities, including hypertension, DM, ischaemic stroke, ischaemic progressive PAH in elderly patients histologically. Guidelines do not heart disease, atrial fibrillation, obesity, and CKD. Hoper et al. describe PAH in elderly individuals with multimorbidity; therefore, claimed they camouflage non-specific symptoms of PAH—such as fa- diagnosis and management were based on the procedure for young tigue—which leads to diagnostic delay. Our patient had most of these 1,3,4 or middle-aged patients. If PH is likely, diagnostic evaluations such comorbidities, which may have contributed to delayed suspicion and as PFT should be performed to exclude Group 2 or 3 PH. Guidelines . performance of specific tests for PAH. then recommend a ventilation/perfusion scan to evaluate CTEPH; if . While specific drug therapy for PAH comprises three different sig- CTEPH is unlikely, RHC—and additional studies including magnetic . nalling pathways, elderly patients often undergo less aggressive treat- . 8 resonance imaging and specific serology testing—are considered to . ment. Some studies have demonstrated a worse prognosis in elderly . 8,9 classify PAH. In our case, pulmonary findings on imaging and histology . patients than in young or middle-aged patients. According to the may suggest Group 3 PH; however, her PFT showed a mild restrictive . UK/Ireland registry, 1-, 2-, 3-, and 5-year survival rates in patients pattern with disproportionately reduced DLCO, which could not ex- . >50 years old were 90%, 75.5%, 57.1%, and 43.7%, respectively. plain severe PH. Additionally, GGO is present in more than one-third . We did not use the continuous intravenous prostacyclin analogues 6 . of PAH patients; thus, we concluded the patient had Group 1 PH which is the 1st line therapy of WHO-FC IV PAH, as the patient with concomitant lung disease, rather than PH due to lung disease refused; consequently, symptoms rapidly progressed within (Group 3 PH). 3 months. Clinicians must recognize the condition of elderly patients 4 M. Yokose et al. Figure 2 Trans-thoracic echocardiography (TTE) revealed right ventricular dilatation with flattening of the interventricular septum (A)and increased tricuspid regurgitation pressure gradient (54 mmHg) (B). Follow-up TTE on Day 19 revealed worsened tricuspid regurgitation pressure gradient (81 mmHg) (C) despite the patient losing body weight due to diuretic therapy (D). Figure 3 Contrast-enhanced computed tomography of the chest with three-dimensional reconstruction detected no pulmonary embolism (A; frontal view, B; right anterior oblique view). Pulmonary angiography showed no narrowing or obstruction of the pulmonary artery (C; right middle and lower lobe segment in frontal view, D; left lingual and lower lobe segment in frontal view). An autopsy case of pulmonary arterial hypertension 5 Figure 4 Association between sequential combination therapy, tricuspid regurgitation pressure gradient, and body weight. BW, body weight; TRPG, tricuspid regurgitation pressure gradient. Figure 5 Autopsy findings (A and B). Smaller pulmonary arterioles exhibit cellular intimal proliferation resulting in prominent luminal stenosis (A: Haematoxylin and eosin staining, 400). (B) Masson Trichrome staining, 400.(C) Emphysematous pulmonary parenchyma and intra-alveolar aggre- gates of macrophages (haematoxylin and eosin staining, 100 ). (D) Mildly thickened alveolar septa and focal fibrosis with chronic inflammatory cell infiltration (Masson Trichrome staining, 200). 6 M. Yokose et al. might deteriorate quickly; therefore, early suspicion and comprehen- . Slide sets: A fully edited slide set detailing this case and suitable for sive diagnostic tests are critical for better management. . local presentation is available online as Supplementary data. Consent: The authors confirm that written consent for submission and publication of this case report including images and associated Conclusions text has beenobtained from the patient’s familyinline withCOPE Pulmonary arterial hypertension is seen in young or middle-aged . guidance. adults, as well as elderly people. Its diagnosis and management are Conflict of interest: None declared. challenging; therefore, a high index of suspicion and early comprehen- . Funding: None declared. sive tests are essential for better patient outcomes. References 1. Sitbon O, Howard L. Management of pulmonary arterial hypertension in patients Lead author biography . aged over 65 years. Eur Heart J Suppl 2019;21:K29–K36. 2. Pugh ME, Sivarajan L, Wang L, Robbins IM, Newman JH, Hemnes AR. Causes of Dr Masashi Yokose is a PGY5 doctor pulmonary hypertension in the elderly. Chest 2014;146:159–166. enrolling in the internal medicine fel- 3. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A et al.; ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of lowships at Dokkyo Medical pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment University Hospital in Japan. He . . of Pulmonary Hypertension of the European Society of Cardiology (ESC) and worked at Dokkyo Medical the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart University Nikko Medical Center to and Lung Transplantation (ISHLT). Eur Heart J 2016;37:67–119. receive training in cardiology and . 4. Frost A, Badesch D, Gibbs JSR, Gopalan D, Khanna D, Manes A et al. Diagnosis nephrology in 2020. His main inter- of pulmonary hypertension. Eur Respir J 2019;53:1801904. 5. Aryal SR, Sharifov OF, Lloyd SG. Emerging role of cardiovascular magnetic res- ests are general internal medicine . onance imaging in the management of pulmonary hypertension. Eur Respir Rev and critical care. . 2020;29:190138. 6. Rajaram S, Swift AJ, Condliffe R, Johns C, Elliot CA, Hill C et al. CT features of . pulmonary arterial hypertension and its major subtypes: a systematic CT evalu- ation of 292 patients from the ASPIRE Registry. Thorax 2015;70:382–387. 7. Hoeper MM, Simon R Gibbs J. The changing landscape of pulmonary arterial Supplementary material hypertension and implications for patient care. Eur Respir Rev 2014;23:450–457. 8. Hjalmarsson C, Ra ˚degran G, Kylhammar D, Rundqvist B, Multing J, Nisell MD Supplementary material is available at European Heart Journal - Case et al. Impact of age and comorbidity on risk stratification in idiopathic pulmonary Reports online. . arterial hypertension. Eur Respir J 2018;51:1702310. 9. Hoeper MM, Huscher D, Ghofrani HA, Delcroix M, Distler O, Schweiger C et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol 2013;168:871–880. . 10. Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JS et al. Changing Acknowledgements demographics, epidemiology, and survival of incident pulmonary arterial hyper- We would like to thank Editage (www.editage.com) for English lan- . tension: results from the pulmonary hypertension registry of the United guage editing. Kingdom and Ireland. Am J Respir Crit Care Med 2012;186:790–796. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal - Case Reports Oxford University Press

An autopsy case of pulmonary arterial hypertension in an elderly patient with multimorbidity: a case report

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Abstract

CASE REPORT European Heart Journal - Case Reports (2022) 6(1), 1–6 https://doi.org/10.1093/ehjcr/ytab527 Heart failure An autopsy case of pulmonary arterial hypertension in an elderly patient with multimorbidity: a case report 1 1 2 1 Masashi Yokose , Takashi Tomoe , Takehiko Yamaguchi , and Takanori Yasu * 1 2 Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University Nikko Medical Center, 632 Takatoku, Nikko, Tochigi 321-2593, Japan; and Department of Pathology, Dokkyo Medical University Nikko Medical Center, 632 Takatoku, Nikko, Tochigi 321-2593, Japan Received 4 June 2021; first decision 26 July 2021; accepted 22 December 2021; online publish-ahead-of-print 28 December 2021 Background There is an increasing number of elderly patients with pulmonary arterial hypertension (PAH), and their characteristics differ from those of young or middle-aged patients with this condition. ................................................................................................ ................................................................................................ ........................... Case summary A 73-year-old woman with a history of myocardial infarction and cardiovascular risk factors was admitted to the hospital with 2-week exertional dyspnoea. Her initial diagnosis was heart failure with preserved ejection fraction, but the symp- toms persisted despite receiving treatment with diuretics. Additional tests showed a significant decrease in diffusing cap- acity of carbon monoxide and findings suggestive of severe pulmonary hypertension (PH). Contrast-enhanced computed tomography of the chest, and pulmonary angiography, showed no narrowing or obstruction of the pulmonary arteries. Right heart catheterization revealed haemodynamic data implying pre-capillary PH. Her condition gradually deteriorated to World Health Organization functional class IV, and sequential combination therapy with tadalafil, macitentan, and selex- ipag was initiated with a PAH diagnosis; however, she died 1 month later. Pathological findings in autopsy were consistent with PAH, and some parts of the lungs revealed the presence of obstructive and interstitial lung disease. ................................................................................................ ................................................................................................ ........................... Discussion The majority of elderly patients with PAH might have multimorbidity. However, there is no specific treatment strategy. It is associated with diagnostic delay and worse prognosis; therefore, early suspicion and comprehensive tests, including right heart catheterization, are essential for better management. Keywords Case report Elderly patients Multimorbidity Pulmonary arterial hypertension • • • ................................................................................................ ................................................................................................ ........................... ESC Curriculum 9.6 Pulmonary hypertension 7.1 Haemodynamic instability Introduction Learning points The number of elderly patients with pulmonary arterial Pulmonary arterial hypertension (PAH) usually occurs in young adult 1,2 hypertension is increasing. They have multimorbidity and women. Diagnosis requires comprehensive investigation to identify worse prognosis compared with younger patients. . classification, severity, and aetiology. The current treatment strategy • . Pulmonaryarterial hypertensioninelderly patients might is based on disease severity; in severe cases, guidelines recommend deteriorate rapidly and its diagnosis is challenging; therefore, a specific drug therapy. Recently, the number of PAH in elderly high index of suspicion and early comprehensive tests are . patients has been increasing. Herein, we report an autopsy case of essential for better management. PAH in an elderly patient with multimorbidity. * Corresponding author. Tel: þ81(288)76-1515, Fax: þ81(288)76-1030, Email: tyasu@dokkyomed.ac.jp Handling Editor: Marta Cvijic Peer-reviewers: Sherif Mohammad Abd ElSamad; Mohammad El Tahlawi and Kyriakos Dimitriadis Compliance Editor: Brett Sydney Bernstein Supplementary Material Editor: Mariame Chakir V The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unre- stricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 2 M. Yokose et al. She lost 4 kg of weight within 4 days; however, her symptoms sus- Timeline tained. Arterial blood gas analysis while breathing ambient air . revealed a PaCO of 37 mmHg, PaO of 61.4 mmHg, SaO of 91.7%, 2 2 2 and alveolar-arterial oxygen gradient of 42.7 mmHg. The pulmonary Day 1 Patient was admitted with a history of 2-week exer- function test (PFT) showed a reduced forced vital capacity (FVC) of tional dyspnoea [World Health Organization func- 1.82 L (73.6% of predicted), reduced forced expiratory volume in 1 s tional classification (WHO-FC) II]. Tricuspid (FEV1) of 1.39 L (72.7% of predicted), mildly reduced FEV1/FVC of regurgitation pressure gradient (TRPG) was 54 76.3%, and markedly reduced diffusing capacity of carbon monoxide mmHg on trans-thoracic echocardiogram (TTE). (DLCO) of 5.76 mL/min/mmHg (30.4% of predicted). The 6 min Day 19 Follow-up TTE showed worsened TRPG (81 mmHg). walking test revealed reduced distance (88 m) and temporarily Day 36 Right heart catheterization revealed a mean pulmonary declined SpO (80%). arterial pressure of 58 mmHg, pulmonary vascular On the 19th day of admission, follow-up TTE showed a markedly resistance of 20 Wood units, and normal pulmonary hypokinetic and enlarged RV (40 mm), with decreased systolic func- arterial wedge pressure. . tion (tricuspid annular plane systolic excursion, 13.4 mm) and wors- Day 56 The patient experienced presyncope and significant . ened TRPG (81 mmHg; Figure 2C and D); estimated RAP remained hypotension during rehabilitation (WHO-FC IV). . 8 mmHg. Peak tricuspid regurgitation velocity was 4.5 m/s, consistent Day 60–90 The patient was treated with sequential triple combin- . with a high probability of pulmonary hypertension (PH). Contrast- ation therapy; however, the condition deteriorated. . enhanced chest CT detected no pulmonary embolism (Figure 3A and Day 94 The patient died. B). Right heart catheterization (RHC) revealed elevated mean pul- monary arterial pressure (58 mmHg) and pulmonary vascular resist- ance (20 Wood units), normal mean pulmonary arterial wedge . pressure (13 mmHg), and cardiac output/cardiac index (3.2 L/min and Case presentation . 2 . 1.9 L/min/m ), respectively. Vasoreactivity testing and fluid challenge . were not performed. There was no significant increase in oxygen sat- A 73-year-old obese woman (body mass index, 29.2 kg/m ) pre- uration between arterial and venous blood samples. Pulmonary angi- sented with 2-week exertional dyspnoea. Medical history included in- ferior myocardial infarction treated with percutaneous coronary ography demonstrated no narrowing or obstruction (Figure 3C and D). Coronary angiography was almost unremarkable except for 75% intervention in the proximal right coronary artery 17 years ago, dysli- stenosis in the distal left circumflex artery. She was diagnosed with pidaemia, hypertension, type 2 diabetes mellitus (DM), and stage 3 1,2 pre-capillary PH, and PAH was highly suspected. Additional tests chronic kidney disease (CKD); there was no relevant family history. for serum anti-human immunodeficiency virus antibody and autoanti- She had a 72-pack-year smoking history until age 56. Medications . included aspirin, carvedilol, rosuvastatin, losartan, nifedipine, isosor- . bodies associated with connective tissue diseases were all negative. . She was unable to undergo a ventilation/perfusion lung scan to ex- bide mononitrate, glimepiride, metformin, empagliflozin, and . clude chronic thrombo-embolic PH (CTEPH) due to presyncope, alogliptin. . progressive dyspnoea at rest, and significant hypotension. She was On physical examination, the patient appeared healthy: her heart diagnosed as World Health Organization functional class (WHO-FC) rate was 77 b.p.m.; blood pressure, 124/66 mmHg; respiratory rate, 18 breath per minute; and percutaneous oxygen saturation (SpO ), IV and treated with sequential combination therapy—including tada- 2 . 95% on 2 L of oxygen. Cardiopulmonary examinations were normal, lafil (20 mg/day, phosphodiesterase type 5 inhibitor) and macitentan (10 mg/day, endothelin receptor antagonist) after 2 weeks—which and laboratory data revealed elevated brain natriuretic peptide was ineffective (Figure 4 and Supplementary material online, Table (818 pg/mL). Electrocardiography showed sinus rhythm and inverted T waves in leads II, III, aVF, and V (Figure 1A). Chest radiography S1). The third medication—selexipag (oral prostacyclin receptor 1, 2 . revealed cardiomegaly, while chest computed tomography (CT) . agonist)—was added, its dose gradually increased; however, the without contrast showed bilateral pleural effusion and subpleural . patient’s respiratory status rapidly deteriorated on the 90th day of . admission. She refused intubation and died 4 days later. ground-glass opacity (GGO; Figure 1B and C). . An autopsy after 30 h (Figure 5A–D) revealed medial thickening Trans-thoracic echocardiography (TTE) revealed a normal sized, . and prominent luminal stenosis due to cellular intimal proliferation of hypertrophic (wall thickness, 12 mm) left ventricle (LV) with normal ejection fraction (65%), cardiac output (4.15 L/min), and cardiac index pulmonary arterioles, especially the smaller ones. Furthermore, there (2.28 L/min/m ); and signs of diastolic dysfunction (mitral E/A, 0.70; were emphysematous parenchymal changes, thickened alveolar mitral E velocity deceleration time, 285 ms; average E/ e, 18.9). The septa, and focal fibrosis, consistent with organizing pneumonia. Many lymphocytes and macrophages infiltrated alveoli. The enlarged heart right ventricle (RV) was hypertrophic and dilated, with a flattened interventricular septum and increased tricuspid regurgitation pres- exhibited focal fibrosis and myocardial fascicular arrangement of the sure gradient (TRPG, 54 mmHg; Figure 2A and B). The estimated right LV posterior wall, consistent with old myocardial infarction. The RV atrial pressure (RAP) was 8 mmHg, and the inter-arterial septum . wall was hypertrophic and mildly dilated. Focal amyloid deposits at remained intact. The patient was diagnosed with heart failure with . hyalinized islets of Langerhans in the pancreas, renal arteriosclerosis, preserved ejection fraction, and furosemide (10 mg/day) was and arteriolosclerosis, and scattered globally sclerotic glomeruli indi- administered. cated DM. An autopsy case of pulmonary arterial hypertension 3 Figure 1 Electrocardiography showed sinus rhythm and inverted T waves in leads II, III, aVF, and V (A). Chest computed tomography without 1, 2 contrast revealed bilateral pleural effusion and right-dominant subpleural ground-glass opacity from the apex (B)to base (C). Hjalmarsson et al. previously reported about 20% of elderly Discussion . patients >65 years old with idiopathic PAH have at least four comor- Currently, there are only a few case reports which confirmed rapidly bidities, including hypertension, DM, ischaemic stroke, ischaemic progressive PAH in elderly patients histologically. Guidelines do not heart disease, atrial fibrillation, obesity, and CKD. Hoper et al. describe PAH in elderly individuals with multimorbidity; therefore, claimed they camouflage non-specific symptoms of PAH—such as fa- diagnosis and management were based on the procedure for young tigue—which leads to diagnostic delay. Our patient had most of these 1,3,4 or middle-aged patients. If PH is likely, diagnostic evaluations such comorbidities, which may have contributed to delayed suspicion and as PFT should be performed to exclude Group 2 or 3 PH. Guidelines . performance of specific tests for PAH. then recommend a ventilation/perfusion scan to evaluate CTEPH; if . While specific drug therapy for PAH comprises three different sig- CTEPH is unlikely, RHC—and additional studies including magnetic . nalling pathways, elderly patients often undergo less aggressive treat- . 8 resonance imaging and specific serology testing—are considered to . ment. Some studies have demonstrated a worse prognosis in elderly . 8,9 classify PAH. In our case, pulmonary findings on imaging and histology . patients than in young or middle-aged patients. According to the may suggest Group 3 PH; however, her PFT showed a mild restrictive . UK/Ireland registry, 1-, 2-, 3-, and 5-year survival rates in patients pattern with disproportionately reduced DLCO, which could not ex- . >50 years old were 90%, 75.5%, 57.1%, and 43.7%, respectively. plain severe PH. Additionally, GGO is present in more than one-third . We did not use the continuous intravenous prostacyclin analogues 6 . of PAH patients; thus, we concluded the patient had Group 1 PH which is the 1st line therapy of WHO-FC IV PAH, as the patient with concomitant lung disease, rather than PH due to lung disease refused; consequently, symptoms rapidly progressed within (Group 3 PH). 3 months. Clinicians must recognize the condition of elderly patients 4 M. Yokose et al. Figure 2 Trans-thoracic echocardiography (TTE) revealed right ventricular dilatation with flattening of the interventricular septum (A)and increased tricuspid regurgitation pressure gradient (54 mmHg) (B). Follow-up TTE on Day 19 revealed worsened tricuspid regurgitation pressure gradient (81 mmHg) (C) despite the patient losing body weight due to diuretic therapy (D). Figure 3 Contrast-enhanced computed tomography of the chest with three-dimensional reconstruction detected no pulmonary embolism (A; frontal view, B; right anterior oblique view). Pulmonary angiography showed no narrowing or obstruction of the pulmonary artery (C; right middle and lower lobe segment in frontal view, D; left lingual and lower lobe segment in frontal view). An autopsy case of pulmonary arterial hypertension 5 Figure 4 Association between sequential combination therapy, tricuspid regurgitation pressure gradient, and body weight. BW, body weight; TRPG, tricuspid regurgitation pressure gradient. Figure 5 Autopsy findings (A and B). Smaller pulmonary arterioles exhibit cellular intimal proliferation resulting in prominent luminal stenosis (A: Haematoxylin and eosin staining, 400). (B) Masson Trichrome staining, 400.(C) Emphysematous pulmonary parenchyma and intra-alveolar aggre- gates of macrophages (haematoxylin and eosin staining, 100 ). (D) Mildly thickened alveolar septa and focal fibrosis with chronic inflammatory cell infiltration (Masson Trichrome staining, 200). 6 M. Yokose et al. might deteriorate quickly; therefore, early suspicion and comprehen- . Slide sets: A fully edited slide set detailing this case and suitable for sive diagnostic tests are critical for better management. . local presentation is available online as Supplementary data. Consent: The authors confirm that written consent for submission and publication of this case report including images and associated Conclusions text has beenobtained from the patient’s familyinline withCOPE Pulmonary arterial hypertension is seen in young or middle-aged . guidance. adults, as well as elderly people. Its diagnosis and management are Conflict of interest: None declared. challenging; therefore, a high index of suspicion and early comprehen- . Funding: None declared. sive tests are essential for better patient outcomes. References 1. Sitbon O, Howard L. Management of pulmonary arterial hypertension in patients Lead author biography . aged over 65 years. Eur Heart J Suppl 2019;21:K29–K36. 2. Pugh ME, Sivarajan L, Wang L, Robbins IM, Newman JH, Hemnes AR. Causes of Dr Masashi Yokose is a PGY5 doctor pulmonary hypertension in the elderly. Chest 2014;146:159–166. enrolling in the internal medicine fel- 3. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A et al.; ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of lowships at Dokkyo Medical pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment University Hospital in Japan. He . . of Pulmonary Hypertension of the European Society of Cardiology (ESC) and worked at Dokkyo Medical the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart University Nikko Medical Center to and Lung Transplantation (ISHLT). Eur Heart J 2016;37:67–119. receive training in cardiology and . 4. Frost A, Badesch D, Gibbs JSR, Gopalan D, Khanna D, Manes A et al. Diagnosis nephrology in 2020. His main inter- of pulmonary hypertension. Eur Respir J 2019;53:1801904. 5. Aryal SR, Sharifov OF, Lloyd SG. Emerging role of cardiovascular magnetic res- ests are general internal medicine . onance imaging in the management of pulmonary hypertension. Eur Respir Rev and critical care. . 2020;29:190138. 6. Rajaram S, Swift AJ, Condliffe R, Johns C, Elliot CA, Hill C et al. CT features of . pulmonary arterial hypertension and its major subtypes: a systematic CT evalu- ation of 292 patients from the ASPIRE Registry. Thorax 2015;70:382–387. 7. Hoeper MM, Simon R Gibbs J. The changing landscape of pulmonary arterial Supplementary material hypertension and implications for patient care. Eur Respir Rev 2014;23:450–457. 8. Hjalmarsson C, Ra ˚degran G, Kylhammar D, Rundqvist B, Multing J, Nisell MD Supplementary material is available at European Heart Journal - Case et al. Impact of age and comorbidity on risk stratification in idiopathic pulmonary Reports online. . arterial hypertension. Eur Respir J 2018;51:1702310. 9. Hoeper MM, Huscher D, Ghofrani HA, Delcroix M, Distler O, Schweiger C et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol 2013;168:871–880. . 10. Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JS et al. Changing Acknowledgements demographics, epidemiology, and survival of incident pulmonary arterial hyper- We would like to thank Editage (www.editage.com) for English lan- . tension: results from the pulmonary hypertension registry of the United guage editing. Kingdom and Ireland. Am J Respir Crit Care Med 2012;186:790–796.

Journal

European Heart Journal - Case Reports – Oxford University Press

Published: Dec 28, 2021

Keywords: Case report; Elderly patients; Multimorbidity; Pulmonary arterial hypertension

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