ABSTRACT
BACKGROUND: In Romania, 23 patients have been diagnosed with hereditary transthyretin amyloidosis (ATTRh), 18 of whom have the Glu54Gln mutation. This retrospective cohort included all patients with Glu54Gln-mutated ATTRh who were diagnosed in Romania from 2005 to 2018. RESULTS: Of 18 patients, 10 were symptomatic, five were asymptomatic carriers and three died during the study. All originated from North-East Romania. Median age at symptom onset was 45 years; median age at death was 51 years. All patients had cardiac involvement, including changes in biomarkers (mean N-terminal-pro B-type natriuretic peptide: 2815.6 pg/ml), electrocardiography (15% atrial fibrillation, 38% atrioventricular block, 31% right bundle block), and echocardiography (mean interventricular septum: 16 mm, mean left ventricular ejection fraction: 49%). Scintigraphy showed myocardial radiotracer uptake in all patients. In addition, 92% of patients had polyneuropathy at diagnosis and 53% had carpal tunnel syndrome; 69% exhibited orthostatic hypotension and 31% suffered from diarrhea. No renal or liver involvement was observed. CONCLUSIONS: This is the largest Glu54Gln-mutated ATTRh cohort diagnosed to date, and to our knowledge the first describing this variant worldwide. Clinical features of this variant are early onset, neurological and cardiac involvement, aggressive disease progression and short survival. Early diagnosis and therapeutic intervention have potential to improve prognosis in ATTRh.
Subject(s)
Amyloid Neuropathies, Familial , Amyloidosis, Familial , Cardiomyopathies , Amyloid Neuropathies, Familial/genetics , Humans , Prealbumin , Retrospective Studies , RomaniaSubject(s)
Amyloid Neuropathies, Familial/physiopathology , Heart Failure/physiopathology , Prealbumin/genetics , Adolescent , Adult , Amyloid Neuropathies, Familial/genetics , Female , Heart Failure/complications , Heart Failure/genetics , Heart Septum/pathology , Humans , Male , Middle Aged , Mutation , Young AdultABSTRACT
RATIONALE: Acute ST-segment elevation myocardial infarction (STEMI) is a rare complication of acute ischemic stroke (AIS) during thrombolytic therapy. We report a case of STEMI occurring 40âminutes after thrombolytic therapy for AIS and discuss the possible mechanisms and therapeutic approaches. PATIENT CONCERNS: A 87-year-old woman with a history of arterial hypertension was admitted for acute onset of right-sided limb weakness 2âhours before arrival at the emergency department. Forty minutes after intravenous recombinant tissue plasminogen activator (i.v. rtPA) administration for AIS, STEMI occurred (signaled by a third-degree atrioventricular block). DIAGNOSES: The diagnoses were AIS and STEMI. Coronary angiography confirmed right coronary artery occlusion. INTERVENTIONS: Four hours after the onset of STEMI, stenting was performed, normalizing the coronary blood flow. OUTCOMES: The patient died 2 days thereafter because of persistent cardiogenic shock. LESSONS: Our case is remarkable owing to the unusually early (<1âhour) occurrence of STEMI after i.v. rtPA administration. A third-degree atrioventricular block after thrombolysis for AIS could signal a STEMI onset. New and ongoing trials are assessing whether adjunct administration of direct thrombin inhibitors of rtPA in the first 24âhours after thrombolysis for AIS can prevent early recurrent ischemic events.
Subject(s)
ST Elevation Myocardial Infarction/etiology , Stroke/complications , Stroke/drug therapy , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Aged, 80 and over , Female , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/therapeutic use , Humans , Shock, Cardiogenic/etiology , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Tomography, X-Ray Computed/methodsABSTRACT
OBJECTIVES: The aim of this study was to evaluate the association between interleukin (IL)-6 and IL-10 gene polymorphism and the short-term risk of postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgery and also to evaluate the endothelial function. METHODS AND RESULTS: We determined preoperatively IL-6 gene polymorphism (-174 G/C and nt565 G/A), IL-10 polymorphism (-1082G/A, -819C/T, -592C/A), and brachial artery vasodilatation using ultrasound in 48 patients undergoing vascular surgery. Eight patients (16.7%) developed over a period of 30 days cardiovascular events (cardiovascular death, resuscitated cardiac arrest, acute myocardial infarction, unstable angina, stroke). Cardiovascular events were more frequent in the subgroups of patients with genotypes associated with high serum levels of IL-6: -174CC (57.14% vs 12.5% for -174GC genotype and 8% for -174GG, P = .007) and nt565AA (50% vs 17.6% for nt565GA genotype and 8% for nt565GG genotype, P = .021) and in subgroups with haplotypes associated with low serum levels of IL-10: ATA (57.14% vs 14.8% for haplotype ACC and 7.4% for GCC, GCA, GTA, GTC haplotypes, P = .004). Flow-mediated dilatation was significantly lower in patients with IL-6 -174CC genotype (7.05% +/- 1.49% vs 8.41% +/- 1.9% for IL-6 -174GC and 9.42% +/- 2.46% for IL-6 -174GG, P = .009) and IL-6 nt565AA genotype (7.14 +/- 1.61% vs 8.49% +/- 1.91% for IL-6 nt565GA and 9.42% +/- 2.46% for IL-6 nt565GG, P = .018) and in patients with IL-10ATA haplotype (6.45% +/- 0.57% vs 9.13% +/- 2.52% for IL-10ACC and 9.24% +/- 2.09% for IL-10 GCC/GCA/GTA/GTC, P = .004) respectively. CONCLUSIONS: IL-6 -174CC and nt565AA genotypes and IL-10ATA haplotypes are correlated with a high short-term risk of acute postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgical revascularization and with endothelial dysfunction in these patients.
