Initial single-center experience of a standardized protocol for invasive assessment of ischemia and non-obstructive coronary artery disease.

INTRODUCTION: Coronary vasomotion disorders (CVDs), including microvascular angina (MVA) and vasospastic angina (VSA), account for significant morbidity among patients with non-obstructive coronary artery disease (NOCAD). However, protocols for CVD assessment in clinical practice are seldom standardized and may be difficult to implement. PURPOSE: To assess the safety and feasibility of a comprehensive coronary function test (CFT) protocol for assessment of CVD and the prevalence of different phenotypes of CVD in patients with angina and NOCAD (ANOCA). METHODS: Patients with persistent angina referred for invasive coronary angiogram and found to have NOCAD were prospectively recruited and underwent a CFT. Functional parameters (fractional flow reserve, coronary flow reserve and index of myocardial resistance) and coronary vasoreactivity were assessed in all patients. RESULTS: Of the 20 patients included, the mean age was 63±13 years and 50% were females. Most patients had persistent typical angina and evidence of ischemia in noninvasive tests (75%). The CFT was successfully performed in all subjects without serious complications. Isolated MVA was found in 25%, isolated VSA in 40%, both MVA and VSA in 10% and noncardiac chest pain in 25% of patients. Antianginal therapy was modified after the results of CFT in 70% of patients. CONCLUSION: A coronary function test was feasible and safe in a cohort of patients with ANOCA. CVD were prevalent in this selected group of patients, and some presented mixed CVD phenotypes. CFT may provide a definitive diagnosis in patients with persistent angina and prompt the stratification of pharmacological therapy.

Index of microcirculatory resistance in the assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Coronary microvascular dysfunction (CMD) is one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). The index of microcirculatory resistance (IMR) is an invasive method to assess the coronary microcirculation. The aim was to assess CMD in patients with HCM by IMR. METHODS: Adult patients with HCM without epicardial coronary artery disease underwent cardiac catheterization for the assessment of CMD by IMR (normal cut-off value ≤22.0) and coronary flow reserve (CFR) (normal cut-off value ≥2). Cardiovascular magnetic resonance (CMR) was performed to assess the ischemic burden by perfusion imaging during regadenoson-induced hyperemia, and the extent of myocardial fibrosis was assessed by late gadolinium enhancement (LGE), native T1 mapping and extracellular volume (ECV). RESULTS: Fourteen patients were enrolled with a mean age of 62.8±6.2years, 8 (57.1%) males, of whom 9 (64.3%) had obstructive HCM. Using IMR, CMD was detected in 4 (29%) patients. Among four patients with an IMR>22.0, all had non-obstructive HCM and two had angina. CFR<2 was reported in eight patients (57%). Concordance between IMR and CFR (both normal or both abnormal) was verified in 6 patients (43%). Among four patients with IMR>22.0, perfusion defects were found in two of the three patients who underwent stress CMR. Increased ECV (>28%) was documented in two of the patients with IMR>22 and in three of the patients with IMR≤22.0. LGE was >15% in 2 of the patients with IMR>22 and in 4 with IMR≤22.0. CONCLUSIONS: IMR assessment in HCM is feasible and safe. Patients with abnormal IMR seemed to have more significant tissue abnormalities on CMR.

Large Morgagni Hernia in an Adult Patient.

A 70-year-old woman presented to the emergency department with symptoms of a lower respiratory infection. A chest x-ray showed enlargement of the mediastinal space. The patient was admitted with a respiratory tract infection and started on antibiotic treatment. A computed tomography (CT) scan of the thorax revealed a large diaphragmatic hernia with stomach, large intestine and caudal pancreas lodged in the thoracic cavity. After the antibiotic treatment, the patient became asymptomatic and surgery repair was declined. Morgagni hernia is an uncommon type of congenital diaphragmatic hernia, which may be asymptomatic until late in life or may be present acutely with life threatening conditions. LEARNING POINTS: Morgagni hernia is the most rare form of congenital hernia, representing 2 to 3% of all cases.Chronic respiratory symptoms or gastrointestinal disturbances can be the only manifestation.Most asymptomatic cases in adults are found after doing chest x-ray for unrelated problems.

Yellow Nail Syndrome: Report of Two Cases and a Brief Review of the Current Literature.

Yellow Nail Syndrome (YNS) is a rare, and probably misdiagnosed, condition. It must be considered in middle-aged patients with unexplained chronic respiratory manifestations, lymphedema and nail abnormalities. We present two cases of undiagnosed YNS until the current admissions, despite several years of investigation. The authors wish to draw attention to this syndrome, of which diagnosis is clinical and of exclusion. LEARNING POINTS: Yellow nail syndrome is characterized by abnormal nails, lymphedema and respiratory manifestation.Diagnosis is clinical and should raise the suspicion of underlying medical conditions. The treatment is symptomatic.

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model.

BACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

Impact of syncope on quality of life: validation of a measure in patients undergoing tilt testing.

INTRODUCTION AND OBJECTIVES: Recurrent syncope has a significant impact on quality of life. The development of measurement scales to assess this impact that are easy to use in clinical settings is crucial. The objective of the present study is a preliminary validation of the Impact of Syncope on Quality of Life questionnaire for the Portuguese population. METHODS: The instrument underwent a process of translation, validation, analysis of cultural appropriateness and cognitive debriefing. A population of 39 patients with a history of recurrent syncope (>1 year) who underwent tilt testing, aged 52.1 ± 16.4 years (21-83), 43.5% male, most in active employment (n=18) or retired (n=13), constituted a convenience sample. The resulting Portuguese version is similar to the original, with 12 items in a single aggregate score, and underwent statistical validation, with assessment of reliability, validity and stability over time. RESULTS: With regard to reliability, the internal consistency of the scale is 0.9. Assessment of convergent and discriminant validity showed statistically significant results (p<0.01). Regarding stability over time, a test-retest of this instrument at six months after tilt testing with 22 patients of the sample who had not undergone any clinical intervention found no statistically significant changes in quality of life. CONCLUSIONS: The results indicate that this instrument is of value for assessing quality of life in patients with recurrent syncope in Portugal.

Invasive assessment of the coronary microcirculation using the index of microcirculatory resistance: description and validation of an animal model.

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-µm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

[Tilt training increases vasoconstrictor reserve in patients with neurocardiogenic syncope]. / O treino de ortostatismo (tilt training) aumenta a reserva vasoconstritora em doentes com síncope reflexa neurocardiogénica.

UNLABELLED: Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. OBJECTIVE: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. METHODS: We studied 28 patients (50% male, mean age 41±14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60° - 6 sessions, 70° - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10° head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24±12 months). RESULTS: Over the course of the TT program there was a significant increase in total peripheral resistance (1485±225 vs. 1591±187 dyn·s·cm(-5), p<0.05), with a decrease in standard deviation (206±60 vs. 150±42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0±3.2/patient in the 12 months before TT vs. 1.4±0.8/patient post-TT, p<0.05). CONCLUSION: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance.