Changes in aortic root function after valve replacement in patients with aortic stenosis.

BACKGROUND: Aortic elastic properties are compromised in various states that induce functional and histological changes in the aortic wall. Aortic stenosis is frequent and often requires replacement of the stenotic valve. The purpose of this study was to examine the effect of aortic valve replacement on the aortic root function. METHODS: 31 patients, mean+/-SD age 67.2+/-9.1 years with severe aortic stenosis, who underwent aortic valve replacement with a bileaflet mechanical prosthesis, were studied. Aortic root function indices such as aortic cross-sectional compliance (CSC), aortic root distensibility (ARD), and aortic stiffness index (ASI) were calculated with the use of M-mode echocardiography in three sessions: one preoperatively (pre-op), one on day 7 postoperatively (early post-op), and one 6 months postoperatively (late post-op). RESULTS: Aortic root function deteriorated early post-op (p<0.001 for all) and returned towards pre-op levels late post-op (p=NS for all). CSC changed from 2.84+/-1.98 to 1.37+/-0.92, and 2.30+/-1.11 cm2/mmHg, ARD from 2.21+/-5.60 to 1.01+/-0.67, and 1.79+/-0.96 cm2/dyne, and ASI from 9.72+/-5.60 to 24.65+/-19.10, and 11.51+/-7.85, respectively. Correlations were found between early changes in some aortic root indices and the degree of aortic stenosis, denoting that aortic function deteriorated less in more severe cases of aortic stenosis. None of the late changes were related to aortic valve or left ventricular indices. CONCLUSIONS: Aortic valve replacement with a mechanical valve results in a significant but transient impairment of aortic distensibility.

Embolic stroke after "cured" prosthetic aortic valve endocarditis.

The authors report on the case of a patient with infective endocarditis of a prosthetic valve in the aortic position, after receiving percutaneous transluminal coronary angioplasty. Transesophageal echocardiography provided valuable information about the existence and size of vegetations at the time of initial diagnosis and during followup. Despite successful treatment resulting in good control of the infection and a significant reduction of vegetation size, the patient still suffered a major cerebral embolic event early after hospital discharge.

Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings.

IMPORTANCE: Newer sequencing technologies in combination with traditional gene mapping techniques, such as linkage analysis, can help identify the genetic basis of disease for patients with rare disorders of uncertain etiology. This approach may expand the phenotypic spectrum of disease associated with those genetic mutations. OBJECTIVE: To elucidate the molecular cause of a neuromuscular disease among a family in which 4 members, a mother and her 3 sons, were affected. DESIGN, SETTING, AND PARTICIPANTS: Two of 4 affected members manifested nemaline myopathy, a common subtype of congenital myopathy, while the other 2 had a nonspecific myopathy. Single-nucleotide polymorphism-based linkage analysis was performed on DNA samples from the 4 affected family members, and whole-genome sequencing was performed in the proband. Real-time quantitative reverse transcription-polymerase chain reaction, immunofluorescence, and Western blot analysis were performed on muscle biopsy specimens. MAIN OUTCOMES AND MEASURES: Whole-genome sequencing and linkage analysis identified a variant in a gene that explains the phenotype. RESULTS: We identified a novel neurofilament light polypeptide (NEFL) nonsense mutation in all affected members. NEFL mutations have been previously linked to Charcot-Marie-Tooth disease in humans. This led us to reevaluate the diagnosis, and we recognized that several of the findings, especially those related to the muscle biopsy specimens and electromyography, were consistent with a neurogenic disease. CONCLUSIONS AND RELEVANCE: NEFL mutations are known to cause Charcot-Marie-Tooth disease in humans and motor neuron disease in mice. We report the identification of an NEFL mutation in a family clinically manifesting congenital myopathy. We also describe potential overlap between myopathic and neurogenic findings in this family. These findings expand the phenotypic spectrum of diseases associated with NEFL mutations. This study is an example of the power of genomic approaches to identify potentially pathogenic mutations in unsuspected genes responsible for heterogeneous neuromuscular diseases.

A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia.

The constellation of clinico-pathological and laboratory findings including massive hepatomegaly, steatosis, and marked hypertriglyceridemia in infancy is extremely rare. We describe a child who is presented with the above findings, and despite extensive diagnostic testing no cause could be identified. Whole exome sequencing was performed on the patient and parents' DNA. Mutations in GPD1 encoding glycerol-3-phosphate dehydrogenase that catalyzes the reversible redox reaction of dihydroxyacetone phosphate and NADH to glycerol-3-phosphate (G3P) and NAD(+) were identified. The proband inherited a GPD1 deletion from the father determined using copy number analysis and a missense change p.(R229Q) from the mother. GPD1 protein was absent in the patient's liver biopsy on western blot. Low normal activity of carnitine palmitoyl transferases, CPT1 and CPT2, was present in the patient's skin fibroblasts, without mutations in genes encoding for these proteins. This is the first report of compound heterozygous mutations in GPD1 associated with a lack of GPD1 protein and reduction in CPT1 and CPT2 activity.

Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition.

KCNJ8 (NM_004982) encodes the pore forming subunit of one of the ATP-sensitive inwardly rectifying potassium (KATP) channels. KCNJ8 sequence variations are traditionally associated with J-wave syndromes, involving ventricular fibrillation and sudden cardiac death. Recently, the KATP gene ABCC9 (SUR2, NM_020297) has been associated with the multi-organ disorder Cantú syndrome or hypertrichotic osteochondrodysplasia (MIM 239850) (hypertrichosis, macrosomia, osteochondrodysplasia, and cardiomegaly). Here, we report on a patient with a de novo nonsynonymous KCNJ8 SNV (p.V65M) and Cantú syndrome, who tested negative for mutations in ABCC9. The genotype and multi-organ abnormalities of this patient are reviewed. A careful screening of the KATP genes should be performed in all individuals diagnosed with Cantú syndrome and no mutation in ABCC9.

Successful thrombolysis of a partially obstructed bileaflet prosthetic heart valve in the mitral position.

We describe the case of a woman who presented with dyspnea of abrupt onset and who had recently undergone replacement of the mitral valve with a bileaflet mechanical prosthesis. Transthoracic echocardiographic examination with spectral Doppler recording of transvalvular blood flow revealed a velocity spectrum consistent with obstruction. Transesophageal echocardiography demonstrated partial obstruction of the prosthetic valve due to immobilization of 1 hemidisc in the closed position. This immobilization was apparently caused by a small mass whose appearance was consistent with that of a thrombus. The patient was successfully treated by intravenous administration of a thrombolytic agent. This case demonstrates the value of transesophageal echocardiography in the selection of candidates for thrombolytic treatment in cases of thrombosis of a left-sided valve prosthesis.