Transthyretin cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: experience of a single center.

BACKGROUND: Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset. We report our single center experience on ATTR-CA detection among TAVR candidates to provide insights on the prevalence and clinical features of dual pathology as compared to lone AS. METHODS: Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: "ATTR-CA+": patients with confirmed ATTR-CA at DPD bone scintigraphy; "ATTR-CA-": patients with negative DPD bone scintigraphy or a negative RAISE score; "ATTR-CA indeterminate": patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA- patients were compared. RESULTS: Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in six. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA-, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1% (95% CI 2.6-14.7%). As compared to ATTR-CA - patients, ATTR-CA + patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, we describe for the first time bifascicular block as an ECG feature highly specific of patients with dual pathology (50.0% vs. 2.7%, P<0.001). Of note, pericardial effusion was rarely found in patients with lone AS (16.7% vs. 1.2%, P=0.027). No difference in procedural outcomes was observed between groups. CONCLUSIONS: Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features might lead to selective DPD bone scintigraphy with a satisfactory positive predictive value.

In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis.

BACKGROUND: One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients. CLINICAL CASE: We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively. CONCLUSION: In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

Noncardiac chest pain of esophageal origin in patients with and without coronary artery disease.

BACKGROUND/AIMS: Non-cardiac chest pain is a frequent finding in patients admitted to emergency departments, and it has been shown that many of these patients may have an esophageal cause for their pain. However, little data are available on patients primarily referred to the cardiology unit, and especially those with coronary artery disease. The purpose of this study was to assess the role of esophageal dysfunction in chest pain patients with and without coronary artery disease. METHODOLOGY: Eighty-one patients referred from a cardiology unit for chest pain and no myocardial infarction entered the study. Sixty-one patients had no evidence of coronary artery disease, whereas 20 had coronary artery disease with chest pain at rest. After the cardiological evaluation, the patients underwent esophageal function testing by means of upper endoscopy, manometry, and 24-hour pH-monitoring. RESULTS: Overall, 10% of patients (2.5% in the coronary artery disease group) had evidence of endoscopic esophagitis, 46% of esophageal motor disorders (12% in the coronary artery disease group), and 10% abnormal pH-monitoring (1% in the coronary artery disease group). CONCLUSIONS: We report that the esophagus might be responsible for non-cardiac chest pain in patients with and without coronary artery disease. In our experience, esophageal motor disorders, and not an increased acid reflux, are the abnormalities most commonly found in these patients.

Exhaled nitric oxide during exercise and dobutamine stress echocardiography in patients with mitral stenosis.

BACKGROUND: Pulmonary hypertension (PH) is an important limiting factor of exercise tolerance in patients with mitral stenosis (MS). We wished to investigate the relationship between respiratory nitric oxide (NO), a potent vasodilator, and exercise tolerance in patients with moderate MS. In the same patients, we wondered whether acute change in pulmonary hemodynamics could affect respiratory NO. METHODS: Ten patients with moderate MS (valve area 1.4+/-0.2 cm(2)) were studied at rest, during incremental cycle ergometry exercise, and during dobutamine stress echocardiography (DSE). The concentration of NO in exhaled air (FE(NO)) and NO output (V'(NO)) were measured at baseline, at the end of exercise, and at the end of DSE. Eight healthy subjects served as normal controls for NO output during exercise. RESULTS: During exercise, FE(NO) decreased both in patients and in controls, while V'(NO) increased in both. At the end of exercise, both VO(2) max and V'(NO) were significantly higher in controls than in patients. The increase in V'(NO) during exercise was significantly correlated with VO(2) max, both in patients and in controls. During DSE, cardiac output (CO), pulmonary artery pressure (PAP), and mitral valve gradient increased. No changes in mean FE(NO), V'(NO), or ventilation were observed during DSE. There was a significant inverse correlation between FE(NO) and mitral valve gradient at the end of DSE. CONCLUSIONS: In patients with moderate MS, exercise performance is correlated with respiratory NO output. In the same patients, during DSE, the increase in CO, which is not accompanied by an increase in ventilation, is not associated with an increase in respiratory V'(NO).