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The study describes all patients in Denmark with vascular Ehlers–Danlos syndrome (vEDS). Carriers of pathogenic or likely pathogenic COL3A1 variants were retrospectively identified through registries and specialized clinics. Medical records were reviewed for vascular‐ or organ ruptures and invasive procedures performed. Identified families were divided by variant type (null, splice, and missense) and familial phenotypes (severe or attenuated). Families in which at least one carrier has suffered a major event before the age of 30 were classified as severe, whereas families in which at least three carriers had reached the age of 40 without a major event were classified as attenuated. Eighty‐seven persons (59 still alive) from 25 families were included with a mean observation time of 44 years. Sixty‐seven percent of patients could be subclassified in a familial phenotype. Thirty‐one major events were observed. Eleven complications in 172 invasive procedures were recorded. No fatal complications to elective surgery were observed. The type of COL3A1 variant did not reliably predict phenotype, but a pattern of intrafamilial consistency emerged with some families showing an attenuated form of vEDS. Elective medical procedures appear to be safer than previously thought, although data only allow for conclusions regarding individuals from families with the attenuated form of vEDS. [ABSTRACT FROM AUTHOR]

Background Truncating variants in titin (TTNtv) are the most common cause of dilated cardiomyopathy (DCM). We evaluated the genotype-phenotype correlation in TTNtv-DCM, with a special focus on long-term outcomes, arrhythmias, response to treatment and sex-related presentation. Methods Data on patient characteristics and outcomes were collected retrospectively from electronic health records of patients genotyped at two Danish heart transplantation centres. Results We included 115 patients (66% men). At diagnosis of DCM, mean age was 46±13 years and left ventricular ejection fraction (LVEF) was 28%±13%. During a median follow-up of 7.9 years, 26% reached a composite outcome of left ventricular assist device implantation, heart transplantation or death. In 20% an arrhythmia preceded the DCM diagnosis. In total, 43% had atrial fibrillation (AF) and 23% had ventricular arrhythmias. Long-term left ventricular reverse remodelling (LVRR; LVEF increase ≥10% points or normalisation) was achieved in 58% and occurred more frequently in women (72% vs 51%, p=0.042). In multivariable proportional hazards analyses, occurrence of LVRR was a strong independent negative predictor of the composite outcome (HR: 0.05 (95% CI 0.02 to 0.14); p<0.001). Female sex independently predicted lower rates of ventricular arrhythmias (HR: 0.33 (95% CI 0.11 to 0.99); p=0.05), while the location of the TTNtv was not associated with cardiovascular outcomes. Conclusion DCM caused by TTNtv presented in midlife and was associated with a high burden of AF and ventricular arrhythmias, which often preceded DCM diagnosis. Furthermore, LVRR occurred in a high proportion of patients and was a strong negative predictor of the composite outcome. Female sex was positively associated with occurrence of LVRR and longer event-free survival. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3 tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. Methods and results  In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3 tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94–30.02, P  = 8.05e−11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3 tv (OR 16.17, 95% CI 10.31–24.87, P  < 2.2e−16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3 tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n  = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP−), ALPK3 tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P  < 0.001) and of a short PR interval (10%, P  = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP− and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3 tv died of heart failure or had cardiac transplantation (log-rank P  = 0.012 vs. SP− and P  = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. Conclusions  Heterozygous ALPK3 tv are pathogenic and segregate with a characteristic HCM phenotype. [ABSTRACT FROM AUTHOR]

A case of circulatory collapse due to severe heart failure is reported in a 52-year old male with autoimmune disorders in the form of type-1 diabetes, Graves' disease and total alopecia.Upon admission, the patient had severe heart failure with a cardiac index of 0.9 l/min/m(2), a mixed venous saturation of 29% and left ventricular ejection fraction of 5%. The condition was refractory to treatment with inotropic agents and required mechanical cardiopulmonary support. Endomyocardial biopsies revealed extensive giant cell myocarditis (GCM). Immunosuppressant treatment did not alter the condition and urgent orthotopic heart transplantation was performed.Histopathological examination of the explanted heart confirmed the diagnosis and showed widespread vascular deposition of complement C4d suggesting a pathogenic role for the innate immune system in GCM.At 1-year follow-up the patient was in New York Heart Association (NYHA) class I, had episodes of sustained ventricular tachycardia but showed no evidence of GCM recurrence in endomyocardial biopsies.

Acute adrenal insufficiency is a life threatening disease with dehydration, hypotension, cerebral dysfunction and gastrointestinal symptoms accompanied by low plasma sodium and high plasma potassium. Osmotic demyelination syndrome (ODS) can occur rarely following correction of plasma sodium. We describe a case with extremely low plasma sodium and subsequent development of ODS. Correction which is too slow may lead to cerebral oedema, brain stem herniation and low sodium encephalopathy. Correction which is too fast may cause ODS. The dilemma is accentuated by concomitant Addison crisis.

A 78-year-old male without pre-existing comorbidity who underwent revision of a hip arthroplasty developed abdominal pain and distension, diarrhoeas, pyrexia and leucocytosis after only 5 days' postoperative treatment with cefuroxime and gentamycine. Abdominal computed tomography demonstrated severe colonic dilation, inflammation and oedema consistent with toxic megacolon. Stool samples were positive for Clostridium difficile. Oral vancomycine treatment and colonic decompression were inefficient. Subtotal colectomy was performed after which the condition improved.