Giovanni Storto

Hemodynamic determinants of exercise-induced abnormal blood pressure response in hypertrophic cardiomyopathy

OBJECTIVES We sought to assess the hemodynamics of exercise in patients with hypertrophic cardiomyopathy (HCM), with and without an exercise-induced abnormal blood pressure (BP) response, by ambulatory radionuclide monitoring of left ventricular (LV) function with the VEST device (Capintec Inc., Ramsey, New Jersey). BACKGROUND Blood pressure fails to increase >20 mm Hg during exercise in about one-third of patients with HCM. This carries a high risk of sudden death. METHODS Forty-three patients with HCM and 14 control subjects underwent maximal symptom-limited exercise on a treadmill during VEST. The VEST data were averaged for 1 min and analyzed at baseline, 3 min and peak exercise. The LV end-diastolic, end-systolic and stroke volumes, cardiac output and systemic vascular resistance were expressed as the percentage of baseline. RESULTS Ejection fraction and stroke volume fell in patients with HCM, although they increased in control subjects (p < 0.001 and p = 0.002, respectively). Cardiac output increased significantly more in control subjects than in patients with HCM (p = 0.001). In 17 patients with HCM (39%) with an abnormal BP response, ejection fraction and stroke volume fell more (p = 0.032 and p = 0.009, respectively) and cardiac output increased less (p = 0.001) than they did in patients with HCM with a normal BP response. Systemic vascular resistance decreased similarly in patients with HCM, irrespective of the BP response. CONCLUSIONS In patients with HCM with and without an abnormal BP response, abnormal hemodynamic adaptation to exercise was qualitatively similar but quantitatively different. An abnormal BP response was associated with exercise-induced LV systolic dysfunction. This causes hemodynamic instability, associated with a high risk of sudden cardiac death.

Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril.

OBJECTIVE This study compares the effects of an AT1 angiotensin II receptor antagonist (valsartan) with those of an ACE inhibitor (enalapril) on left ventricular (LV) diastolic function in patients with mild or moderate essential hypertension and no evidence of LV hypertrophy at echocardiography. METHODS A total of 24 patients (16 men, mean age 47 +/- 8 years) underwent radionuclide ambulatory monitoring (Vest) of LV function at rest and during upright bicycle exercise testing before and after two 4-week treatment periods with valsartan (80-160 mg/day orally) and enalapril (20-40 mg/day orally) according to a double-blind, crossover randomization scheme. RESULTS In the overall population no differences between the two treatments were found in LV peak filling rate (PFR) either at rest or at peak exercise. In a subgroup analysis it was found that baseline PFR was normal (= 2.5 EDV/sec) in 12 patients (subgroup A) and impaired (< 2.5 EDV/sec) in the remaining 12 (subgroup B). In both subgroups, valsartan and enalapril induced a significant and comparable reduction of systolic and diastolic blood pressure. In subgroup A, valsartan and enalapril did not induce significant changes in PFR. In subgroup B, valsartan increased PFR both at rest (from 2.0 +/- 0.3 to 2.4 +/- 0.3 EDV/sec, P < 0.01) and at peak exercise (from 4.1 +/- 1.1 to 4.4 +/- 1.0 EDV/s, P < 0.05), whereas enalapril did not change PFR either at rest (2.0 +/- 0.4 EDV/s, P < 0.01 versus valsartan) or at peak exercise (3.7 +/- 1.1 EDV/sec, P < 0.05 versus valsartan). CONCLUSIONS Valsartan-induced renin-angiotensin system blockade is able to improve LV filling in patients with mild or moderate essential hypertension and impaired diastolic function. These findings support the hypothesis of a contribution of the renin-angiotensin system in the control of LV diastolic function in these patients.

Assessment of coronary flow reserve using single photon emission computed tomography with technetium 99m-labeled tracers

The quantitative assessment of coronary flow reserve (CFR) may be useful for the functional evaluation of coronary artery disease (CAD), allowing judgment of its severity, tracking of disease progression, and evaluation of the anti-ischemic efficacy of therapeutic strategies. Invasive techniques, such as intracoronary Doppler ultrasound and the pressure-derived method, which directly assess CFR velocity and fractional flow reserve, have been used for the evaluation of the physiologic significance of coronary lesions. Considerable progress has been made in the improvement of technologies directed toward the noninvasive quantification of myocardial blood flow and CFR. Positron emission tomography has emerged as an accurate technique to quantify CFR. The absolute measurements obtained with this noninvasive approach have been widely validated. Nevertheless, it has not been applied to routine studies because of its high cost and complexity. On the other hand, technetium 99m-labeled tracers have been largely used for the evaluation of myocardial perfusion with single photon emission computed tomography (SPECT) imaging in patients with suspected or known CAD. Recently, attempts to estimate CFR with SPECT tracers have been made to obtain, with noninvasive methods, data for quantitative functional assessment of CAD. This review analyzes the relative merit and limitations of CFR measurements by cardiac SPECT imaging with Tc-99m-labeled tracers and describes the potential clinical applications of this technique.

F-18 FDG PET/CT quantization parameters as predictors of outcome in patients with diffuse large B-cell lymphoma

We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) obtained by F‐18 FDG PET/CT (PET/CT) in patients with diffuse large B‐cell Lymphomas (DLBCL) presenting intermediate IPI score.

Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

PurposeTo investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (TD) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC).MethodsA survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr), respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot) from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif), was estimated.ResultsThe averages of TD were 77 (27-90)95% days in LEGFr and 8.8 (7.3-11.0)95% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed.ConclusionsA higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck sub-site.

Prediction of improvement in global left ventricular function in patients with chronic coronary artery disease and impaired left ventricular function: rest thallium-201 SPET versus low-dose dobutamine echocardiography

Abstract. Accurate assessment of myocardial viability permits selection of patients who would benefit from myocardial revascularization. Currently, rest-redistribution thallium-201 scintigraphy and low-dose dobutamine echocardiography are among the most used techniques for the identification of viable myocardium. Thirty-one consecutive patients (all men, mean age 60±8 years) with chronic coronary artery disease and reduced left ventricular ejection fraction (31%±7%) were studied. Rest 201Tl single-photon emission tomography (SPET), low-dose dobutamine echocardiography and radionuclide angiography were performed before revascularization. Radionuclide angiography and echocardiography were repeated after revascularization. An a/dyskinetic segment was considered viable on 201Tl SPET when tracer uptake was >65%, while improvement on low-dose dobutamine echocardiography was considered a marker of viability. Increase in global ejection fraction was considered significant at ≥5%. In identifying viable segments, rest 201Tl SPET showed higher sensitivity than low-dose dobutamine echocardiography (72% vs 53%, P<0.05), while specificity was not significantly different (86% vs 88%). In 17 patients, global ejection fraction increased ≥5% (group 1) while in 14 it did not (group 2). A higher number of a/dyskinetic segments were viable on 201Tl SPET in group 1 than in group 2 (2.6±1.9 vs 0.6±1.2, P<0.005), while no significant differences were observed on low-dose dobutamine echocardiography (1.7±1.6 vs 1.1±1.6). A significant correlation was found between the number of a/dyskinetic segments viable on 201Tl SPET and post-revascularization changes in ejection fraction (r=0.52, P<0.05), but such a correlation was not observed for low-dose dobutamine echocardiography. Using as the cut-off the presence of at least one viable a/dyskinetic segment, rest 201Tl SPET had a higher sensitivity (82% vs 53%, P=0.07) and showed a trend towards higher accuracy and specificity (77% vs 58%, and 71% vs 64%, respectively) as compared with low-dose dobutamine echocardiography. In conclusion, these findings suggest that when severely reduced global function is present, rest 201Tl SPET evaluation of viability is more accurate than low-dose dobutamine echocardiography for the identification of patients who will benefit most from revascularization.

Relations of left ventricular mass and systolic function to endothelial function and coronary flow reserve in healthy, new discovered hypertensive subjects

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47±10 years old, 26.6±2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (β=−0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (β=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.

Colorectal cancer and 18FDG-PET/CT: What about adding the T to the N parameter in loco-regional staging?

AIM To evaluate whether FDG-positron emission tomography (PET)/computed tomography (CT) may be an accurate technique in the assessment of the T stage in patients with colorectal cancer. METHODS Thirty four consecutive patients (20 men and 14 women; mean age: 63 years) with a histologically proven diagnosis of colorectal adenocarcinoma and scheduled for surgery in our hospital were enrolled in this study. All patients underwent FDG-PET/CT preoperatively. The primary tumor site and extent were evaluated on PET/CT images. Colorectal wall invasion was analysed according to a modified T classification that considers only three stages (≤ T2, T3, T4). Assessment of accuracy was carried out using 95% confidence intervals for T. RESULTS Thirty five/37 (94.6%) adenocarcinomas were identified and correctly located on PET/CT images. PET/CT correctly staged the T of 33/35 lesions identified showing an accuracy of 94.3% (95% CI: 87%-100%). All T1, T3 and T4 lesions were correctly staged, while two T2 neoplasms were overstated as T3. CONCLUSION Our data suggest that FDG-PET/CT may be an accurate modality for identifying primary tumor and defining its local extent in patients with colorectal cancer.

Assessment of Metabolic Response to Radioimmunotherapy with 90Y–Ibritumomab Tiuxetan in Patients with Relapsed or Refractory B-Cell Non–Hodgkin Lymphoma

PURPOSE To prospectively compare the assessment of metabolic response to yttrium 90 ((90)Y)-ibritumomab tiuxetan radioimmunotherapy (RIT) by using fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomographic-computed tomographic (PET/CT) imaging at 2 and 6 months to determine the most appropriate time to detect therapeutic response in refractory non-Hodgkin lymphoma (NHL) patients treated with RIT. MATERIALS AND METHODS The ethical committee of the university approved the protocol and all patients signed informed consent. Twenty-three consecutive patients (10 women, 13 men; mean age, 51.8 years +/-7.3 [standard deviation]) treated by using RIT for relapsed or refractory follicular NHL were enrolled. For all patients, (18)F FDG PET/CT scanning was performed at baseline and at 2 and 6 months after RIT. Response was assessed by using the International Workshop Criteria (IWC) and revised criteria (IWC + PET) as well as the criteria of the European Organization for Research and Treatment of Cancer. One-way analysis of variance for repeated measures, receiver operator curve analysis, and Kaplan-Meier curves were used for statistical analysis. RESULTS PET/CT performed at 2 months revealed complete (n = 12) or partial (n = 4) metabolic response in 16 of 23 patients with complete or partial clinical response. These findings were all confirmed at 6-month scanning. PET/CT indicated refractory or persistent disease at 2 and 6 months in the remaining seven patients. Better overall survival was observed for patients with a reduction in the maximum standard uptake value of 49% or higher (both at 2 and 6 months after RIT) when compared with those with a decrease of less than 49% (P < .05). CONCLUSION Early assessment of response to RIT by using PET/CT might be useful in the identification of patients needing additional therapeutic strategies.

Diagnostic accuracy of low-dose dobutamine echocardiography in predicting post-revascularisation recovery of function in patients with chronic coronary artery disease: relationship to thallium-201 uptake

Abstract. It is known that contractile reserve may be blunted if perfusion and coronary flow reserve are reduced. Thus, it is conceivable that the predictive accuracy of dobutamine echocardiography may differ according to perfusion tracer uptake. The aim of this study was therefore to assess the relationship between the level of thallium-201 uptake and the accuracy of dobutamine echocardiography in identifying reversible dysfunction. Sixty-nine patients (age 59±8 years, ejection fraction 40%±11%) with chronic coronary artery disease scheduled for coronary revascularisation were studied. All patients underwent rest 201Tl single-photon emission tomography and two-dimensional echocardiography at rest and during low-dose dobutamine infusion on the same day before revascularisation and repeated echocardiography at least 30 days thereafter. At follow-up, recovery of function was observed in 49% of 339 dysfunctional segments. The percentage of segments with post-revascularisation recovery of function and the percentage with contractile reserve increased in parallel with 201Tl uptake both in the total group of segments (χ2=35.5, P<0.0001 and χ2=35.9, P<0.0001, respectively) and among the 183 akinetic segments (χ2=44.4, P<0.0001 and χ2=14.6, P<0.05, respectively). The dysfunctional segments were divided into three groups according to 201Tl uptake: (a) uptake <65%, (b) uptake between 65% and 79%, (c) uptake >80%. The positive predictive value increased significantly with the level of 201Tl uptake, and was suboptimal (46%) in akinetic segments with severely reduced 201Tl uptake. The negative predictive value decreased significantly with 201Tl uptake, and it was less than suboptimal (29%) in akinetic segments with normal tracer uptake. Sensitivity was lower in the subset of akinetic segments (42%–63%) than in all dyssynergic segments (63%–76%), whereas specificity was very high in akinetic segments (80%–84%). It is concluded that the accuracy of low-dose dobutamine echocardiography in predicting reversibility of regional dysfunction varies considerably according to 201Tl uptake at rest and to the severity of regional dysfunction.