Severe Aortic Stenosis: More Than an Imaging Diagnosis.

The definition of severe aortic stenosis has undergone significant change casting a wider net to avoid missing patients who could benefit from valve replacement. The presence or absence of symptoms remains the key decision-making element; however, individuals presently undergoing evaluation are older, more likely asymptomatic, and have lower gradients. Due to numerous potential measurement errors, attention to detail when performing diagnostic testing and understanding their limitations are necessary to render appropriate treatment. Exercise testing adds useful information for individuals with severe aortic stenosis felt to be asymptomatic. Dobutamine echocardiography, in low flow-low gradient aortic stenosis, distinguishes between a myopathic and valvular cause of left ventricular dysfunction. Evaluation of patients when normotensive minimizes measurement errors. The amount of aortic valve calcification adds useful information when the degree of aortic stenosis is uncertain. A good history and physical integrated with high-quality imaging data allows for appropriate clinical treatment decisions for patients with aortic stenosis. The goal is simultaneously to provide aortic valve replacement for patients in need while avoiding overdiagnosis and performance of unnecessary procedures.

A novel technique to manage transcatheter aortic valve embolization.

We report a case of a 69-year-old male who was planned for a transcatheter aortic valve replacement (TAVR) with a 26 mm Sapien 3 Valve (Edwards Lifesciences, Irvine, California) for the treatment of symptomatic severe aortic stenosis. During rapid ventricular pacing and implantation of the TAVR valve, there was a loss of pacing capture and subsequent embolization of the valve into the aortic arch. Retrieval of the embolized valve was attempted unsuccessfully using several techniques. Finally, by using a 34 mm Evolut R Valve (Medtronic, Minneapolis, Minnesota), we were able to secure the embolized valve in the transverse segment of the aortic arch without compromising the branch vessels. To our knowledge, this is the first reported case of using a valve-in-valve approach to fixate an embolized valve in the transverse aorta.

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia.

RATIONALE: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. OBJECTIVES: To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites. METHODS: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. MEASUREMENTS AND MAIN RESULTS: At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. CONCLUSIONS: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.

High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy.

BACKGROUND: Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients. METHODS AND RESULTS: We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; nNO level is typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO levels below or near the PCD cutoff values. Patients with CD aged >6 years show increased respiratory symptoms similar to those seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease controls, and 13 healthy controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing DNAI1 founder mutation. Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Among PCD patients, 2 had known PCD causing CCDC39 and CCDC40 mutations. CONCLUSIONS: Our studies show that CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.