Hepatitis E and diaphragmatic dysfunction: Case series and review of the literature.

INTRODUCTION: The causes of diaphragmatic paresis are manifold. An association between neuralgic amyotrophy (NA) and hepatitis E virus (HEV) infection has been reported. We wondered about the prevalence of diaphragmatic disfunction and hepatitis E infection in our clinic. METHODS: From July 1st, 2020 to August 31st, 2023, patients presenting with diaphragmatic dysfunction and simultaneous clinical symptoms of an acute NA, or a history of NA, as well as patients with previously unexplained diaphragmatic dysfunction were examined for HEV infection. RESULTS: By August 31st, 2023, 13 patients with diaphragmatic dysfunction and HEV infection were diagnosed (4 women, 9 men). Mean age was 59 ± 10 years. Liver values were normal in all patients. The median latency to diagnosis was five months (range: 1-48 months); nine patients, 4 of them with typical symptoms of NA, presented with acute onset three patients showed bilateral diaphragmatic dysfunction. All patients had a positive IgG immunoblot. Seven patients, three with NA, had an elevated hepatitis E IgM titer and six of them also a positive IgM immunoblot. In all cases, O2C hepatitis genotype 3 was identified. In eight cases, all those with a high IgG titer >125, the O2 genotype 1 was also detected. CONCLUSION: NA that shows involvement of the phrenic nerve resulting in diaphragmatic dysfunction and dyspnoea, may be associated with HEV infection. The observation of 13 patients with diaphragmatic dysfunctions and HEV infection within a period of three years indicates a high number of undetected HEV-associated diaphragmatic dysfunction in the population, especially in the absence of NA symptoms. Therefore, even in diaphragmatic dysfunction without NA symptoms and causative damaging event, HEV infection should be considered, as it may represent a subform of NA with only phrenic nerve involvement. Therapy of HEV-associated diaphragmatic dysfunction in the acute phase is an open question. In view of the poor prognosis for recovery, antiviral therapy should be discussed. However, no relevant data are currently available.

[Pulmonary Hypertension and Polycythemia vera]. / Pulmonale Hypertonie und Polycythaemia vera.

INTRODUCTION: Chronic myeloproliferative diseases are rare causes of PH class 5 according to Nice classification 2018. The present case reports show different courses, on the one hand with a primary manifestation of a PH and subsequently a PV, on the other hand with the development of a PH in the context of a PV. CASE REPORTS: 1) At first contact, a 75-year-old female patient who complained progressive dyspnea and had evidence of stress-PH in the right heart catheter. During the course she developed a resting PH of up to 70 mmHg systolic despite initial monotherapy and subsequent dual therapy for PH. After 5 years she had the diagnosis of polycythemia vera, treated with hydroxycarbamide and subsequent phlebotomies. In the further course increasing cardiac decompensation and death. 2) 74-year-old female patient at the time of diagnosis of chronic megakaryocytic-granulocytic myelosis. After 7 years, evidence of polycythemia vera (V617F mutation in the JAK2 gene), a monoclonal gammopathy. In the case of splenomegaly, irradiation of the spleen was carried out and, after 1 year, therapy with ruxolitinib was started. After another 2 years, with increasing dyspnea, pulmonary hypertension (CTEPH) with a PA-mean of 43 mmHg and a PVR of 4.5 WE were detected. With anticoagulation and riociguat therapy exercise capacity and PA pressures were only temporarily improved. Within 1 year restrictive ventilation, hypoxemia, heart failure (EF 45 %) with leading right heart decompensation and cardiorenal syndrome developed. Dialysis showed only short-term recompensation, and the patient died. DISCUSSION: The case reports are characterized by a combination of PV and PH, with different temporal sequence, as well as only a low influence of PH-specific therapy, with subsequent progressive cardiac decompensation. Thus, they reflect the different etiologies, clinical manifestations, and the low therapeutic influence of PH in myeloproliferative disorders. The value of PH-specific therapy remains unclear, especially in view of different pathomechanisms in the genesis of PH. CONCLUSION: Patients with myeloproliferative diseases require screening for PH. In the course of PH, myeloproliferative disease can unmask or develop. The therapeutic influence on PH is limited.

Cardiopulmonary Exercise Testing in Combined Pulmonary Fibrosis and Emphysema.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is a distinct entity among fibrosing lung diseases with a high risk for lung cancer and pulmonary hypertension (PH). Notably, concomitant PH was identified as a negative prognostic indicator that could help with early diagnosis to provide important information regarding prognosis. OBJECTIVES: The current study aimed to determine whether cardiopulmonary exercise testing (CPET) can be helpful in differentiating patients having CPFE with and without PH. METHODS: Patients diagnosed with CPFE in 2 German cities (Hemer and Greifswald) over a period of 10 years were included herein. CPET parameters, such as peak oxygen uptake (peak VO2), functional dead space ventilation (VDf/VT), alveolar-arterial oxygen difference (AaDO2), arterial-end-tidal CO2 difference [P(a-ET)CO2] at peak exercise, and the minute ventilation-carbon dioxide production relationship (VE/VCO2 slope), were compared between patients with and without PH. RESULTS: A total of 41 patients with CPET (22 with PH, 19 without PH) were analyzed. Right heart catheterization was performed in 15 of 41 patients without clinically relevant complications. Significant differences in peak VO2 (861 ± 190 vs. 1,397 ± 439 mL), VO2/kg body weight/min (10.8 ± 2.6 vs. 17.4 ± 5.2 mL), peak AaDO2 (72.3 ± 7.3 vs. 46.3 ± 14.2 mm Hg), VE/VCO2 slope (70.1 ± 31.5 vs. 39.6 ± 9.6), and peak P(a-ET)tCO2 (13.9 ± 3.5 vs. 8.1 ± 3.6 mm Hg) were observed between patients with and without PH (p < 0.001). Patients with PH had significantly higher VDf/VT at rest, VT1, and at peak exercise (65.6 ± 16.8% vs. 47.2 ± 11.6%; p < 0.001) than those without PH. A cutoff value of 44 for VE/VCO2 slope had a sensitivity and specificity of 94.7 and 72.7%, while a cutoff value of 11 mm Hg for P(a-ET)CO2 in combination with peak AaDO2 >60 mm Hg had a specificity and sensitivity of 95.5 and 84.2%, respectively. Combining peak AaDO2 >60 mm Hg with peak VO2/body weight/min <16.5 mL/kg/min provided a sensitivity and specificity of 100 and 95.5%, respectively. CONCLUSION: This study provided initial data on CPET among patients having CPFE with and without PH. CPET can help noninvasively detect PH and identify patients at risk. AaDO2 at peak exercise, VE/VCO2 slope, peak P(a-ET)CO2, and peak VO2 were parameters that had high sensitivity and, when combined, high specificity.

Ventilation Parameters under Adaptive Servo Ventilation: A Comparison on Behalf of CSA-Pattern, BNP/NT-pro-BNP, and Ejection Fraction.

BACKGROUND: The SERVE-HF study has raised questions concerning the higher mortality under adaptive servoventilation. The ventilatory mode was discussed as a possible aggravating factor. OBJECTIVES: We wondered if the data recorded by the adaptive servo-ventilation (ASV)-devices in heart failure patients with CSA-CSR ± OSA are different in terms of respiratory parameters and therapeutic pressures compared to patients with CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP. METHODS: Patients were included, if ASV had normalized respiratory disturbance index in the first night of application and after at least 6 weeks. ASV-device data were analyzed in terms of respiratory rate (RR), min ventilation (MV), endexpiratory (EEP), peak inspiratory pressure (Ppeak) and median pressure. RESULTS: Compared to CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP (n = 25), CSA-CSR- (n = 13) CSA-CSR+OSA-patients (n = 32) with elevated BNP/NT-pro-BNP had higher RR (p < 0.01) in the first night of ASV therapy and during follow-up (15.3 ± 1.3 vs. 17.3 ± 2.4/min) with similar MV (6.5 ± 1.3 vs. 6.6 ± 1.3 L), resulting in significantly lower tidal volumes. EEP (5.6 ± 1.1 vs. 5.5 ± 1.1 hPa), Pmedian and Ppeak (9.8 ± 1.5 vs. 9.7 ± 1.2 hPa) were comparable. Ventilatory parameters were not different between LVEF < 40, 40-49, and ≥50%, neither within the whole group nor the group of CSA-CSR ± OSA and heart failure. CONCLUSION: Patients with heart failure and CSA-CSR ± OSA have higher RRs but similar MV under ASV-therapy than patients with CSA and normal BNP. This indicates higher dead space ventilation. EF was not found to have an influence on the ventilatory parameters.

Obstructive sleep apnoea and non-restorative sleep induced by the interface.

BACKGROUND: There are only few data about the influence of interfaces on restorative sleep and required CPAP/APAP levels in patients with obstructive sleep apnoea (OSA). Observations of obstructive apnoeas when using oro-nasal masks with normalisation of respiratory disturbance index (RDI) under nasal masks and of non-restorative sleep under oro-nasal masks in spite of normal RDI led to a registration of patients with such findings. METHODS: This study is a cohort analysis (June 1, 2006 to April 30, 2014) of patients with OSA using an oro-nasal mask and normalisation of the RDI after changing to a nasal mask and of patients complaining about a non-restorative sleep under an oro-nasal mask despite normal RDI. RESULTS: Sixty-five patients (BMI 32.2 ± 8.1 kg/m(2); 64.4 ± 12.8 years) with OSA (n = 54) and non-restorative sleep with normal RDI (n = 11) under oro-nasal masks were included. In the group of patients with pathologic RDI under oro-nasal masks (n = 54), switching the interface to a nasal mask normalised RDI (31.8 ± 16.3 to 6.0 ± 3.6/h [p < 0.001]) and arousal index (p < 0.001); slow-wave and REM sleep increased (p < 0.05). In the patient group with a pathological RDI under CPAP/APAP therapy (n = 45), the pressure decreased from 9.5 ± 2.2 to 7.3 ± 2.0 cm hPa (p < 0.001), and in the group with normal RDI (n = 11) from 10.1 ± 2.4 to 6.8 ± 1.2 hPa (p < 0.01). CONCLUSION: The usage of an oro-nasal mask can result in a paradoxical induction of obstructive hypopnoeas or apnoeas. Clinicians should be aware of this phenomenon. When adapting patients to a PAP therapy, a nasal mask should be preferred even if patients report mouth breathing.

Prevalence and treatment of central sleep apnoea emerging after initiation of continuous positive airway pressure in patients with obstructive sleep apnoea without evidence of heart failure.

BACKGROUND: This study aimed to assess the prevalence of complex sleep apnoea (CompSA), defined as central sleep apnoea (CSA) emerging after the initiation of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA), in patients with normal brain natriuretic peptide (BNP) levels, along with assessing the prevalence of CSA persisting in such patients after the onset of CPAP therapy. We hypothesised that the prevalence of CompSA and persistent CSA after CPAP initiation would be low in patients with OSA and normal BNP levels. MATERIAL AND METHODS: Between April 2004 and July 2007, CPAP was initiated for all patients with OSA for two nights using a standardised protocol. The prevalence of CompSA syndrome (CompSAS) and persisting CSA [central apnoea index (CAI) >5/h and apnoea-hypopnoea index (AHI) >15/h with >50% central events during CPAP therapy] was prospectively assessed in patients with normal BNP levels. Patients with CompSAS or persisting CSA upon CPAP treatment received adaptive servoventilation (ASV). RESULTS: Of 1,776 patients with OSA receiving CPAP, 28 patients (1.57%) had CSA at the time of CPAP therapy and normal BNP levels. Additionally, 10 patients had CompSAS (0.56%) and 18 patients (1.01%) had persisting CSA. In patients with CompSA or persisting CSA, the AHI was significantly lower with CPAP therapy than at the time of diagnosis (34 ± 15/h vs. 47 ± 20/h, p = 0.005). The CAI increased from 10 ± 10/h to 18/h ± 13/h (p = 0.009) upon initiation of CPAP therapy. ASV reduced the AHI to 6 ± 12/h (p < 0.001) during the first night of use. CONCLUSION: The prevalence of CompSA or persisting CSA in patients with OSA and normal BNP levels who are receiving CPAP therapy is low (1.57%). ASV is an effective treatment for these patients.