Francesco Bandera

Added Value of 99mTc-HMPAO–Labeled Leukocyte SPECT/CT in the Characterization and Management of Patients with Infectious Endocarditis

The clinical performance of the Duke Endocarditis Service criteria to establish the diagnosis of infectious endocarditis (IE) can be improved through functional imaging procedures such as radiolabeled leukocytes (99mTc-hexamethylpropyleneamine oxime [HMPAO]–labeled white blood cells [WBC]). Methods: We assessed the value of 99mTc-HMPAO-WBC scintigraphy including SPECT/CT acquisitions in a series of 131 consecutive patients with suspected IE. Patients with permanent cardiac devices were excluded. 99mTc-HMPAO-WBC scintigraphy results were correlated with transthoracic or transesophageal echocardiography, blood cultures, and the Duke criteria. Results: Scintigraphy was true-positive in 46 of 51 and false-negative in 5 of 51 cases (90% sensitivity, 94% negative predictive value, and 100% specificity and positive predictive value). No false-positive results were found, even in patients with early IE evaluated within the first 2 mo from the surgical procedure. In 24 of 51 patients with IE, we also found extracardiac uptake, indicating septic embolism in 21 of 24. Despite the fact that septic embolism was found in 11 of 18 cases of Duke-definite IE, most of the added value from the 99mTc-HMPAO-WBC scan for decision making was seen in patients in whom the Duke criteria yielded possible IE. The scan was particularly valuable in patients with negative or difficult-to-interpret echocardiographic findings because it correctly classified 11 of 88 of these patients as having IE. Furthermore, 3 patients were falsely positive at echocardiography but correctly negative at 99mTc-HMPAO-WBC scintigraphy: these patients had marantic vegetations. Conclusion: Our results demonstrate the ability of 99mTc-HMPAO-WBC scintigraphy to reduce the rate of misdiagnosed cases of IE when combined with standard diagnostic tests in several situations: when clinical suspicion is high but echocardiographic findings are inconclusive; when there is a need for differential diagnosis between septic and sterile vegetations detected at echocardiography; when echocardiographic, laboratory, and clinical data are contradictory; and when valve involvement (especially of a prosthetic valve) needs to be excluded during febrile episodes, sepsis, or postsurgical infections.

Echocardiography of Right Ventriculoarterial Coupling Combined With Cardiopulmonary Exercise Testing to Predict Outcome in Heart Failure

BACKGROUND Pulmonary hypertension, which is related to right ventricular (RV) failure, indicates a poor prognosis in heart failure (HF). Increased ventilatory response and exercise oscillatory ventilation (EOV) also have a negative impact. We hypothesized that the severity classification of HF and risk prediction could be improved by combining functional capacity with cardiopulmonary exercise testing (CPET) and RV-pulmonary circulation coupling, as evaluated by the tricuspid annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure (PASP) relationship. METHODS Four hundred fifty-nine patients with HF were assessed with Doppler echocardiography and CPET and were tracked for outcome. The subjects were followed for major cardiac events (cardiac mortality, left ventricular assist device implant, or heart transplant). Cox regression and Kaplan-Meier analyses were performed with TAPSE and PASP as individual measures that were then combined into a ratio form. RESULTS The TAPSE/PASP ratio (TAPSE/PASP) was the strongest predictor, whereas the New York Heart Association classification and EOV added predictive value. A four-quadrant group prediction risk was created based on TAPSE (< 16 mm or ≥ 16 mm) vs PASP (< 40 mm Hg or ≥ 40 mm Hg) thresholds and the CPET variables distribution as follows: group A (TAPSE > 16 mm and PASP < 40 mm Hg) presented the lowest risk (hazard ratio, 0.17) and best ventilation; group B exhibited a low risk (hazard ratio, 0.88) with depressed TAPSE (< 16 mm) and normal PASP, a preserved peak oxygen consumption (V.o2), but high ventilation. Group C had an increased risk (hazard ratio, 1.3; TAPSE ≥ 16 mm, PASP ≥ 40 mm Hg), a reduced peak V.o2, and a high EOV prevalence. Group D had the highest risk (hazard ratio, 5.6), the worse RV-pulmonary pressure coupling (TAPSE < 16 and PASP ≥ 40 mm Hg), the lowest peak V.o2, and the highest EOV rate. CONCLUSIONS TAPSE/PASP, combined with exercise ventilation, provides relevant clinical and prognostic insights into HF. A low TAPSE/PASP with EOV identifies patients at a particularly high risk of cardiac events.

Heart rate recovery after the 6 min walk test rather than distance ambulated is a powerful prognostic indicator in heart failure with reduced and preserved ejection fraction: a comparison with cardiopulmonary exercise testing

Heart rate recovery (HRR) appears to be a robust prognostic marker in heart failure (HF). When using the 6 min walk test (6MWT) in HF, distance ambulated is generally the reference prognostic variable. We hypothesized that HRR after the 6MWT would be a better prognostic measure than distance ambulated.

Role of Right Ventricle and Dynamic Pulmonary Hypertension on Determining ΔVO2/ΔWork Rate Flattening: Insights from Cardiopulmonary Exercise Test Combined with Exercise Echocardiography

Background—Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of &Dgr;oxygen consumption (VO2)/&Dgr;Work Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of &Dgr;VO2/&Dgr;WR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. Methods and Results—We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. &Dgr;VO2/&Dgr;WR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold, O2 pulse, impaired VE/VCO2). At univariate analysis, exercise ejection fraction, exercise mitral regurgitation, rest and exercise tricuspid annular plane systolic excursion, exercise systolic pulmonary artery pressure, and exercise cardiac output were all significantly (P<0.05) impaired in group A. The multivariate analysis identified exercise systolic pulmonary artery pressure (odds ratio, 1.06; confidence interval, 1.01–1.11; P=0.01) and exercise tricuspid annular plane systolic excursion (odds ratio, 0.88; confidence interval, 0.80–0.97; P=0.01) as main cardiac determinants of &Dgr;VO2/&Dgr;WR flattening; female sex was strongly associated (odds ratio, 6.10; confidence interval, 2.11–17.7; P<0.01). Conclusions—In patients symptomatic for dyspnea, the occurrence of &Dgr;VO2/&Dgr;WR flattening reflects a significantly impaired functional phenotype whose main cardiac determinants are the excessive systolic pulmonary artery pressure increase and the reduced peak right ventricular longitudinal systolic function.Background—Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of Δoxygen consumption (VO2)/ΔWork Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of ΔVO2/ΔWR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. Methods and Results—We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. ΔVO2/ΔWR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold,...

Interleukin-15 and Soluble Interleukin-15 Receptor α in Coronary Artery Disease Patients: Association with Epicardial Fat and Indices of Adipose Tissue Distribution

Interleukin-15 (IL-15) is a pro-inflammatory cytokine which signals via a specific alpha receptor subunit (IL-15Rα). Increased IL-15 level has been observed in cardiovascular patients and IL-15 immunoreactivity has been detected at vulnerable atherosclerotic plaques. Due to the association between adipose tissue distribution, inflammation and coronary artery disease (CAD), we quantified IL-15 and IL-15Rα in CAD patients with different adiposity and adipose tissue distribution and we evaluated whether epicardial adipose tissue (EAT), a visceral fat depot surrounding and infiltrating myocardium, may be a source of both molecules. IL-15 and IL-15Rα proteins were quantified by enzyme-linked immunosorbent assays. Gene expression of IL-15 and IL-15Rα in EAT depots was evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. Plasmatic IL-15 and IL-15Rα levels were higher in CAD than non-CAD patients. After classification according to adipose tissue distribution, IL-15 was higher in CAD patients with increased abdominal adiposity. Increased level of IL-15Rα was observed both in CAD and non-CAD patients with increased abdominal fat. EAT was a source of IL-15 and IL-15Rα and their expression was higher in CAD patients with increased EAT thickness. In conclusion, our data suggest that circulating levels of IL-15 and IL-15Rα seem to reflect visceral distribution of adipose tissue and that EAT may be a potential source of both IL-15 and IL-15Rα. Future studies on the relationship between IL-15, visceral fat and characteristics of atherosclerotic plaques could help to better understand the complex biology of this cytokine.

Cardiopulmonary Exercise Testing: What Is its Value?

Compared with traditional exercise tests, cardiopulmonary exercise testing (CPET) provides a thorough assessment of exercise integrative physiology involving the pulmonary, cardiovascular, muscular, and cellular oxidative systems. Due to the prognostic ability of key variables, CPET applications in cardiology have grown impressively to include all forms of exercise intolerance, with a predominant focus on heart failure with reduced or with preserved ejection fraction. As impaired cardiac output and peripheral oxygen diffusion are the main determinants of the abnormal functional response in cardiac patients, invasive CPET has gained new popularity, especially for diagnosing early heart failure with preserved ejection fraction and exercise-induced pulmonary hypertension. The most impactful advance has recently come from the introduction of CPET combined with echocardiography or CPET imaging, which provides basic information regarding cardiac and valve morphology and function. This review highlights modern CPET use as a single or combined test that allows the pathophysiological bases of exercise limitation to be translated, quite easily, into clinical practice.

Impact of right ventricular dysfunction on the outcome of heart failure patients undergoing surgical ventricular reconstruction

OBJECTIVES The aim was to assess the impact of right ventricular dysfunction (RVD) on the outcome of heart failure (HF) patients undergoing surgical ventricular reconstruction (SVR). METHODS A total of 324 patients (65 ± 9 years) with previous myocardial infarction had an echocardiographic assessment of right ventricular (RV) function before and after SVR. RV function was assessed measuring the tricuspid annular plane systolic excursion (TAPSE) and RV dysfunction was defined by a TAPSE < 16 mm. RESULTS RV dysfunction was detected in 69 patients (Group A, mean age 64 ± 11 years), while 255 patients (Group B, mean age 65 ± 9 years) had a preserved RV function. Patients in Group A showed a higher New York Heart Association (NYHA) class (P = 0.01), larger left ventricular (LV) end-diastolic and end-systolic volumes (P = 0.01), a lower EF (P = 0.01), a higher percentage of moderate-to-severe mitral regurgitation (P = 0.01) and a higher systolic pulmonary artery pressure (PAPs; P = 0.01). Propensity score matching was applied in order to adjust for baseline differences. In the fully matched population, low-output syndrome (P = 0.01), inotropic support (P = 0.01) and intra-aortic balloon pump insertion (P = 0.03) were significantly more frequent in Group A compared with Group B. However, 30-day mortality was not significantly different between the two groups (P = 0.18). Kaplan-Meier 5- and 8-year survival rate (log-rank: P = 0.01) as well as freedom from cardiac events (log-rank: P = 0.02) were significantly lower in patients with RV dysfunction. At Cox regression analysis, preoperative RVD (P = 0.01) and NYHA class at admission >II (P = 0.02) resulted in independent predictor of late mortality. CONCLUSIONS RV dysfunction correlates with LV dysfunction and it is an important predictor of long-term outcome in HF patients undergoing SVR.

Prevalence and characterization of exercise oscillatory ventilation in apparently healthy individuals at variable risk for cardiovascular disease: A subanalysis of the EURO-EX trial

Introduction There has been a greater appreciation of several variables obtained by cardiopulmonary exercise testing (CPX). Exercise oscillatory ventilation (EOV) is a CPX pattern that has gained recognition as an ominous marker of poor prognosis in cardiac patients. The purpose of the present study is to characterize whether such an abnormal ventilatory pattern may also be detected in apparently healthy subjects and determine its clinical significance. Methods The study involved 510 subjects (mean age 60 ± 14 years; 49% male) with a broad cardiovascular (CV) risk factor profile who underwent CPX. Results The population was divided into two groups according to the presence (17%) or absence of EOV. Subjects with EOV were significantly older and a higher percentage was female. Risk factor profile and medication use was significantly different between subgroups, indicating subjects with EOV had a worse CV risk factor profile and were prescribed CV-focused preventive medications at a significantly higher frequency. Subjects with EOV had comparatively poorer CPX performance and gas exchange phenotype. Multivariate binary logistic regression analysis found being female was the strongest predictor of EOV (odds ratio: 2.77, 95% confidence interval (CI): 1.66-4.61, p < 0.001). A diagnosis of diabetes (odds ratio: 2.40, 95% CI: 1.34–4.15.2, p < 0.001) added significant value for predicting EOV and was retained in the regression. The likelihood for EOV for subjects who were female and diagnosed with diabetes was 3.71 (95% CI 1.88–7.30, p < 0.001). Conclusions This is the first study to examine EOV prevalence and characterization in apparently healthy persons with results supporting an in-depth definition of abnormal exercise phenotypes.

Sildenafil and Exercise Capacity in Heart Failure

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lamas reported receiving a grant and travel support from the National Heart, Lung, and Blood Institute and the National Center for Complementary and Alternative Medicine; and serving as a consultant from 2000-2003 to OmniComm, the electronic data capture company used in TACT; however, no funds were received. Dr Mark reported receiving grants from Mount Sinai Medical Center during the conduct of TACT; for other studies, receiving grants from Gilead, Medtronic, AstraZeneca, Eli Lilly, St Jude, and Bristol-Myers Squibb; and receiving personal fees from Janssen and Milestone outside the submitted work. Dr Lee reported no disclosures.

IL-18 level in patients undergoing coronary artery bypass grafting surgery or valve replacement: which link with epicardial fat depot?

Interleukin-18 (IL-18) is a member of the interleukin-1 family of cytokines produced constitutively by different cell types and by adipose tissue. Due to the link between obesity, inflammation and cardiovascular diseases, we aimed to measure IL-18 circulating level in patients undergoing open-heart surgery both for elective coronary artery bypass grafting (CABG) or for valve replacement (VR), and we also evaluated whether epicardial adipose tissue (EAT) depot may be a potential source of IL-18. Circulating IL-18 protein was quantified by enzyme-linked immunosorbent assay. IL-18, IL-18 receptor 1 (IL-18 Rl) and IL-18 receptor accessory protein (IL-18-RAP) gene expression in EAT depot were evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. In this study we found that all cardiovascular patients (CABG and VR) have increased circulating IL-18 level compared to healthy control subjects (p < 0.0001), but no statistical significant difference was observed between CABG and VR groups (p = 0.35). A great increase in the gene expression of IL-18 (p < 0.05), IL-18 R1 (p < 0.01) and IL-18 RAP (p < 0.001) was observed in EAT samples obtained from CABG vs VR patients. In conclusion, CABG and VR patients had similar increased level of circulating IL-18 protein, but in EAT depots isolated from CABG gene expression of IL-18, IL-18 R1 and IL-18-RAP resulted higher than in VR patients. Future investigation on local IL-18 protein production, its autocrine-paracrine effect and its correlation with plasmatic IL-18 level could give more information on the relationship between IL-18 and coronary artery disease.