The diagnostic performance of quantitative flow ratio and perfusion imaging in patients with prior coronary artery disease.

AIMS: In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD), ischaemia detection by myocardial perfusion imaging (MPI) and an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR) in patients with prior CAD [previous percutaneous coronary intervention (PCI) and/or myocardial infarction (MI)]. METHODS AND RESULTS: This PACIFIC-2 sub-study evaluated 189 CCS patients with prior CAD for inclusion. Patients underwent SPECT, PET, and CMR followed by invasive coronary angiography with fractional flow reserve (FFR) measurements of all major coronary arteries (N = 567), except for vessels with a sub-total or chronic total occlusion. Quantitative flow ratio computation was attempted in 488 (86%) vessels with measured FFR available (FFR ≤0.80 defined haemodynamically significant CAD). Quantitative flow ratio analysis was successful in 334 (68%) vessels among 166 patients and demonstrated a higher accuracy (84%) and sensitivity (72%) compared with SPECT (66%, P < 0.001 and 46%, P = 0.001), PET (65%, P < 0.001 and 58%, P = 0.032), and CMR (72%, P < 0.001 and 33%, P < 0.001). The specificity of QFR (87%) was similar to that of CMR (83%, P = 0.123) but higher than that of SPECT (71%, P < 0.001) and PET (67%, P < 0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, P < 0.001), PET (0.66, P < 0.001), and CMR (0.60, P < 0.001). CONCLUSION: QFR correlated better with FFR in patients with prior CAD than MPI, as reflected in the higher diagnostic performance measures for detecting FFR-defined, vessel-specific, significant CAD.

Left atrial strain is associated with arrhythmia recurrence after atrial fibrillation ablation: Cardiac magnetic resonance rapid strain vs. feature tracking strain.

PURPOSE: The present study assesses different left atrial (LA) strain approaches in relation to atrial fibrillation (AF) recurrence after ablation and compares LA feature tracking (FT) strain to novel rapid LA strain approaches in AF patients. METHODS: This retrospective single-center study comprised of 110 prospectively recruited AF patients who underwent cardiac magnetic resonance (CMR) imaging in sinus rhythm prior to their first pulmonary vein isolation ablation. LA rapid strain (long axis strain and atrioventricular (AV)-junction strain), LA FT strain, and LA volumes were derived from 2-chamber and 4-chamber cine images. AF recurrence was followed up for 12 months using either 12­lead ECGs or rhythm Holter monitoring. RESULTS: Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (122-286) days. LA long axis strain, AV-junction strain, and FT strain were all more impaired in patients with AF recurrence compared to patients without AF recurrence (long axis strain: P < 0.01; AV-junction strain: P < 0.001; FT strain: P < 0.01, respectively). Area under the curve (AUC) values for LA remodeling parameters in association with AF recurrence were 0.68 for long axis strain, 0.68 for AV-junction strain, 0.66 for FT strain, 0.66 for LA volume index. Phasic FT LA strain demonstrated that contractile strain had the highest AUC (0.70). CONCLUSION: Both LA rapid strain and LA FT strain are associated with arrhythmia recurrence after ablation in AF patients. LA rapid strain can be a convenient and reproducible alternative for LA FT strain to assess LA function in clinical practice.

Functional stress imaging to predict abnormal coronary fractional flow reserve: the PACIFIC 2 study.

AIMS: The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58-76%) for SPECT, 81% (72-87%) for PET, and 66% (56-75%) for MRI. Specificity was 61% (48-72%) for SPECT, 65% (53-76%) for PET, and 62% (49-74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68-81%) did not statistically differ from SPECT (65%, 58-72%, P = 0.03) and MRI (64%, 57-72%, P = 0.052). Using FFR < 0.75 as a reference, accuracies increased to 69% (SPECT), 79% (PET), and 71% (MRI). CONCLUSION: In this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.

Too much of a good thing: a case report of traumatic drop attacks and syncope due to orthostatic hypertension.

BACKGROUND: Orthostatic hypertension (OHT) is the clinical opposite to orthostatic hypotension and is an under-recognized and poorly understood clinical phenomenon. Patients may experience disabling symptoms such as dizziness, chest pain, and shortness of breath. In addition, OHT is associated with important clinical outcomes such as silent cerebral infarcts and cognitive decline. CASE SUMMARY: We present the case of a 67-year-old female who experienced frequent drop attacks with and without transient loss of consciousness causing various injuries. A range of standard diagnostic procedures did not yield an explanation for her symptoms but head-up tilt (HUT) testing showed OHT and induced most of her symptoms. Upon initiation of doxazosin, an alpha-blocking drug, she was free of symptoms and blood pressure response was normal on the repeat HUT test. DISCUSSION: To our knowledge, this is the first report of syncope due to OHT. Orthostatic hypertension is a heterogeneous condition and may occur in young, otherwise healthy individuals but also in older patients with cardiovascular comorbidities. It is thought that symptoms occur because of excessive venous pooling (causing a drop in cardiac output) or adrenergic hypersensitivity (resulting in cerebral vasoconstriction or acute rise in cardiac afterload). Since our patient had a marked response to an alpha-blocking agent, we think baroreflex hypersensitivity is the most likely cause of her complaints. Though syncope is probably rare, OHT should be regarded as a possible explanation of orthostatic symptoms.

Endosonography-related mortality and morbidity for pulmonary indications: a nationwide survey in the Netherlands.

BACKGROUND: Endosonography is being implemented rapidly in pulmonary medicine for the diagnosis and staging of lung cancer, the assessment of sarcoidosis, and the assessment of mediastinal lesions. Although serious adverse events (SAEs) have been described, safety data outside cohort studies are scarce. OBJECTIVE: To assess the SAE and mortality rate of EUS-guided FNA (EUS-FNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal and/or hilar analysis. DESIGN: Nationwide, retrospective survey by using questionnaires. SETTING: All hospitals in the Netherlands. PATIENTS: All patients undergoing EUS-FNA and EBUS-TBNA for intrathoracic analysis in the period 1999 to 2011. INTERVENTIONS: EUS-FNA and EBUS-TBNA. MAIN OUTCOME MEASUREMENTS: Occurrence of fatal outcomes and SAEs. Detailed information was obtained for each reported case, and all cases were reviewed independently by 2 investigators, including identification of risk factors. RESULTS: All 89 hospitals (100%) responded. An estimated 14,075 EUS-FNA and 2675 EBUS procedures were performed. Seven patients died after endosonography (5 EUS-FNA, 2 EBUS [mortality rate 0.04%]). All fatalities occurred in patients of poor performance status (American Society of Anesthesiologists Physical Status Classification System score of III/IV). Twenty-five SAEs were reported (22 EUS-FNA, 3 EBUS [SAE rate of 0.15%; EUS-FNA 0.16%, EBUS 0.11%]). SAEs were mostly (64%) of infectious origin. No specific risk factors for infectious adverse events could be identified. LIMITATIONS: Retrospective study, possible recall bias, overrepresentation of EUS-FNA cases. CONCLUSION: Endosonography appears to be a safe technique for the analysis of mediastinal and/or hilar lesions. Poor performance status is a risk factor for fatal outcomes. Mediastinitis and/or mediastinal abscess formation is rare but is a potential and dangerous adverse event of endosonography.

Endosonography for the diagnosis of malignant lymphoma presenting with mediastinal lymphadenopathy.

BACKGROUND: Endosonography combined with fine needle aspiration (FNA) is a minimally invasive technique for intrathoracic mediastinal nodal sampling. The value of endosonography with FNA for the diagnosis of malignant mediastinal lymphoma is under debate. In this study, the sensitivity and negative predictive value of endosonography for the assessment of primary versus recurrent malignant lymphoma were assessed. METHODS: Forty-nine patients with suspected primary (n=32) or recurrent (n=17) lymphoma were retrospectively analyzed. They presented with mediastinal nodal enlargement and underwent endosonography for diagnostic purposes between 2001 and 2011. The final diagnosis was based on surgical biopsy, conclusive cell block analysis, or longstanding clinical and radiologic follow-up. RESULTS: In 33 patients, a final diagnosis of lymphoma was established; in 16 patients (33%) alternative diagnoses (eg, small cell lung cancer, sarcoidosis) were found. Sensitivity and negative predictive value of endosonography in diagnosing primary versus recurrent mediastinal lymphoma were 55% and 57% versus 88% and 90%, respectively. No complications occurred during these procedures. CONCLUSIONS: On the basis of these data, we conclude that endosonography is a minimally invasive, safe, and sensitive method for the assessment of recurrent mediastinal malignant lymphoma or alternative diagnoses but has limitations in assessing a primary lymphoma diagnosis.

Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial.

IMPORTANCE: Tissue verification of noncaseating granulomas is recommended for the diagnosis of sarcoidosis. Bronchoscopy with transbronchial lung biopsies, the current diagnostic standard, has moderate sensitivity in assessing granulomas. Endosonography with intrathoracic nodal aspiration appears to be a promising diagnostic technique. OBJECTIVE: To evaluate the diagnostic yield of bronchoscopy vs endosonography in the diagnosis of stage I/II sarcoidosis. DESIGN, SETTING, AND PATIENTS: Randomized clinical multicenter trial (14 centers in 6 countries) between March 2009 and November 2011 of 304 consecutive patients with suspected pulmonary sarcoidosis (stage I/II) in whom tissue confirmation of noncaseating granulomas was indicated. INTERVENTIONS: Either bronchoscopy with transbronchial and endobronchial lung biopsies or endosonography (esophageal or endobronchial ultrasonography) with aspiration of intrathoracic lymph nodes. All patients also underwent bronchoalveolar lavage. MAIN OUTCOMES AND MEASURES: The primary outcome was the diagnostic yield for detecting noncaseating granulomas in patients with a final diagnosis of sarcoidosis. The diagnosis was based on final clinical judgment by the treating physician, according to all available information (including findings from initial bronchoscopy or endosonography). Secondary outcomes were the complication rate in both groups and sensitivity and specificity of bronchoalveolar lavage in the diagnosis of sarcoidosis. RESULTS: A total of 149 patients were randomized to bronchoscopy and 155 to endosonography. Significantly more granulomas were detected at endosonography vs bronchoscopy (114 vs 72 patients; 74% vs 48%; P < .001). Diagnostic yield to detect granulomas for endosonography was 80% (95% CI, 73%-86%); for bronchoscopy, 53% (95% CI, 45%-61%) (P < .001). Two serious adverse events occurred in the bronchoscopy group and 1 in the endosonography group; all patients recovered completely. Sensitivity of the bronchoalveolar lavage for sarcoidosis based on CD4/CD8 ratio was 54% (95% CI, 46%-62%) for flow cytometry and 24% (95% CI, 16%-34%) for cytospin analysis. CONCLUSION AND RELEVANCE: Among patients with suspected stage I/II pulmonary sarcoidosis undergoing tissue confirmation, the use of endosonographic nodal aspiration compared with bronchoscopic biopsy resulted in greater diagnostic yield. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00872612.

Transesophageal ultrasound-guided fine-needle aspiration for the mediastinal restaging of non-small cell lung cancer.

INTRODUCTION: Selected patients with stage III (N2/N3) non-small cell lung cancer (NSCLC) who are downstaged to N0 by chemoradiation therapy might benefit from subsequent surgical resection of the tumor. How mediastinal lymph nodes can be best reevaluated is subject of debate. Transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive technique to sample mediastinal nodes. We assessed sensitivity and false-negative rate of EUS-FNA for the mediastinal restaging of patients with stage III NSCLC. METHODS: Fifty-eight consecutive patients with stage III NSCLC and tissue-proven lymph node metastases N2/N3) who underwent EUS-FNA for restaging purposes after chemoradiation therapy were retrospectively analyzed. Surgical-pathological staging was used as the reference standard for nodal metastases. RESULTS: EUS-FNA found persistent nodal metastases (N2/N3) in 15 patients (26%). Of the 43 patients without persistent mediastinal metastases at EUS, 33 patients subsequently underwent surgical verification of the mediastinal nodes in whom persistent metastases (yN2/N3) were found in 19 patients (58%), and loco-regional downstaging (yN0) was achieved in the other 14 (42%). The prevalence of persistent nodal metastases in the 48 patients who could be analyzed was 71%. Sensitivity and the false-negative rate of EUS-FNA for mediastinal restaging were 44 and 58%, respectively. DISCUSSION: For mediastinal restaging of stage III NSCLC, EUS-FNA is a minimally invasive and safe method to confirm persistent nodal metastases, but this technique has a low negative predictive value and is therefore not useful for the exclusion of mediastinal metastases. Surgical restaging is indicated in the absence of mediastinal metastases at EUS-FNA.

Transaortic EUS-guided FNA in the diagnosis of lung tumors and lymph nodes.

BACKGROUND: Obtaining tissue from a para-aortal lymph node or tumor is a challenge that currently requires invasive surgical procedures. Para-aortic lung tumors can be clearly visualized by EUS. Although the accessibility of lesions adjacent to the esophagus is well documented, the para-aortic region has never been systematically explored. OBJECTIVE: To assess the feasibility, yield, and safety of transaortic biopsy specimens in the diagnosis of lung tumors and nodal masses located lateral to the aorta. DESIGN: A retrospective case series of 14 consecutive patients. SETTING: Pulmonary Department, Leiden University Medical Center, Leiden, The Netherlands. PATIENTS: Fourteen patients with known or suspected lung cancer. Nine patients presented with a left-sided lung mass (mean size 27 mm), whereas 5 patients had an enlarged para-aortic node (mean size 16 mm). INTERVENTIONS: Real-time EUS-guided transaortic biopsy of a para-aortic lesion. MAIN OUTCOME MEASUREMENTS: Feasibility, diagnostic yield, and complication rates of transaortic EUS-guided FNA (EUS-FNA). RESULTS: The final diagnosis was known in 12 patients (10 non-small-cell lung carcinoma [NSCLC], 1 small-cell lung carcinoma [SCLC], and 1 renal-cell carcinoma). EUS-FNA established malignancy in 9 of 14 patients (64%) (8 NSCLC and 1 SCLC). One aspirate revealed reactive nodal tissue, and 4 demonstrated nonrepresentative material. Malignancy was further assessed in 3 patients after subsequent diagnostics. Transaortic FNA was found to be safe. In 2 patients, EUS images after biopsy were suspicious for a small para-aortic hematoma. These patients recovered uneventfully. CONCLUSIONS: These results demonstrate that a single EUS-guided transaortic biopsy of para-aortic lymph nodes and tumors is a feasible and probably safe method that results in a diagnosis in the majority of cases.