ABSTRACT
Background: TGFB3 variants cause Loeys-Dietz syndrome type 5, a syndromic form of thoracic aortic aneurysm and dissection. The exact disease phenotype is hard to delineate because of few identified cases and highly variable clinical representation. Methodology: We provide the results of a haplotype analysis and a medical record review of clinical features of 27 individuals from 5 different families, originating from the Campine region in Flanders, carrying the NM_003239.5(TGFB3):c.787G>C p.(Asp263His) likely pathogenic variant, dbSNP:rs796051886, ClinVar:203492. The Asp263 residue is essential for integrin binding to the Arg-Gly-Asp (RGD) motif of the TGFß3-cytokine. Results: The haplotype analysis revealed a shared haplotype of minimum 1.92 Mb and maximum 4.14 Mb, suggesting a common founder originating >400 years ago. Variable clinical features included connective tissue manifestations, non-aneurysmal cardiovascular problems such as hypertrophic cardiomyopathy, bicuspid aortic valve, mitral valve disease, and septal defects. Remarkably, only in 4 out of the 27 variant-harboring individuals, significant aortic involvement was observed. In one family, a 31-year-old male presented with type A dissection. In another family, the male proband (65 years) underwent a Bentall procedure because of bicuspid aortic valve insufficiency combined with sinus of Valsalva of 50 mm, while an 80-year-old male relative had an aortic diameter of 43 mm. In a third family, the father of the proband (75 years) presented with ascending aortic aneurysm (44 mm). Conclusion: The low penetrance (15%) of aortic aneurysm/dissection suggests that haploinsufficiency alone by the TGFB3 variant may not result in aneurysm development but that additional factors are required to provoke the aneurysm phenotype.
ABSTRACT
BACKGROUND: Hamman's sign is a rare phenomenon. Louis Hamman described this pathognomonic clicking chest noise in association with pneumomediastinum in 1937. This typical noise can also be present in left-sided pneumothorax. Clinical cases already mention this pericardial knock in 1918 in gunshot wounds of the left chest and in 1928 in cases of spontaneous left-sided pneumothorax. However, the sound itself has only rarely been recorded. CASE SUMMARY: We describe a case of a young man with no significant medical history who was referred to the hospital with chest pain and audible clicks, documented with his smartphone. Imaging studies including chest radiograph and computed tomography scan revealed a left-sided pneumothorax. The patient underwent semi-urgent insertion of a thorax drain. His clinical outcome was excellent. DISCUSSION: In recent years only a few case reports describe Hamman's sign, as it is rare and happens only transiently. This case report includes the audible clicks recorded by the patient with his smartphone. We stress the importance of thoracic clicking sounds as key symptom in the differential diagnosis of left-sided pneumothorax, pneumomediastinum, and valvular pathology such as mitral valve prolapse.
ABSTRACT
AIMS: In the rehabilitation of cardiovascular disease patients a correct determination of the endurance-type exercise intensity is important to generate health benefits and preserve medical safety. It remains to be assessed whether the guideline-based exercise intensity domains are internally consistent and agree with physiological responses to exercise in cardiovascular disease patients. METHODS: A total of 272 cardiovascular disease patients without pacemaker executed a maximal cardiopulmonary exercise test on bike (peak respiratory gas exchange ratio >1.09), to assess peak heart rate (HRpeak), oxygen uptake (VO2peak) and cycling power output (Wpeak). The first and second ventilatory threshold (VT1 and VT2, respectively) was determined and extrapolated to %VO2peak, %HRpeak, %heart rate reserve (%HRR) and %Wpeak for comparison with guideline-based exercise intensity domains. RESULTS: VT1 was noted at 62 ± 10% VO2peak, 75 ± 10% HRpeak, 42 ± 14% HRR and 47 ± 11% Wpeak, corresponding to the high intensity exercise domain (for %VO2peak and %HRpeak) or low intensity exercise domain (for %Wpeak and %HRR). VT2 was noted at 84 ± 9% VO2peak, 88 ± 8% HRpeak, 74 ± 15% HRR and 76 ± 11% Wpeak, corresponding to the high intensity exercise domain (for %HRR and %Wpeak) or very hard exercise domain (for %HRpeak and %VO2peak). At best (when using %Wpeak) in only 63% and 72% of all patients VT1 and VT2, respectively, corresponded to the same guideline-based exercise intensity domain, but this dropped to about 48% and 52% at worst (when using %HRR and %HRpeak, respectively). In particular, the patient's VO2peak related to differently elicited guideline-based exercise intensity domains (P < 0.05). CONCLUSION: The guideline-based exercise intensity domains for cardiovascular disease patients seem inconsistent, thus reiterating the need for adjustment.
