Iacopo Carbone

Clinical Characteristics and Cardiovascular Magnetic Resonance Findings in Stress (Takotsubo) Cardiomyopathy.

CONTEXT Stress cardiomyopathy (SC) is a transient form of acute heart failure triggered by stressful events and associated with a distinctive left ventricular (LV) contraction pattern. Various aspects of its clinical profile have been described in small single-center populations, but larger, multicenter data sets have been lacking so far. Furthermore, it remains difficult to quickly establish diagnosis on admission. OBJECTIVES To comprehensively define the clinical spectrum and evolution of SC in a large population, including tissue characterization data from cardiovascular magnetic resonance (CMR) imaging; and to establish a set of CMR criteria suitable for diagnostic decision making in patients acutely presenting with suspected SC. DESIGN, SETTING, AND PATIENTS Prospective study conducted at 7 tertiary care centers in Europe and North America between January 2005 and October 2010 among 256 patients with SC assessed at the time of presentation as well as 1 to 6 months after the acute event. MAIN OUTCOME MEASURES Complete recovery of LV dysfunction. RESULTS Eighty-one percent of patients (n = 207) were postmenopausal women, 8% (n = 20) were younger women (aged ≤50 years), and 11% (n = 29) were men. A stressful trigger could be identified in 182 patients (71%). Cardiovascular magnetic resonance imaging data (available for 239 patients [93%]) revealed 4 distinct patterns of regional ventricular ballooning: apical (n = 197 [82%]), biventricular (n = 81 [34%]), midventricular (n = 40 [17%]), and basal (n = 2 [1%]). Left ventricular ejection fraction was reduced (48% [SD, 11%]; 95% confidence interval [CI], 47%-50%) in all patients. Stress cardiomyopathy was accurately identified by CMR using specific criteria: a typical pattern of LV dysfunction, myocardial edema, absence of significant necrosis/fibrosis, and markers for myocardial inflammation. Follow-up CMR imaging showed complete normalization of LV ejection fraction (66% [SD, 7%]; 95% CI, 64%-68%) and inflammatory markers in the absence of significant fibrosis in all patients. CONCLUSIONS The clinical profile of SC is considerably broader than reported previously. Cardiovascular magnetic resonance imaging at the time of initial clinical presentation may provide relevant functional and tissue information that might aid in the establishment of the diagnosis of SC.

Thrombus Aspiration During Primary Percutaneous Coronary Intervention Improves Myocardial Reperfusion and Reduces Infarct Size. The EXPIRA (Thrombectomy With Export Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention) Prospective, Randomized Trial

OBJECTIVES The purpose of this study was to evaluate the impact on myocardial perfusion and infarct size as assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM) (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary percutaneous coronary intervention (PPCI) in a subset of patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND PPCI may cause thrombus dislodgment, leading to microvascular damage. METHODS One hundred seventy-five STEMI patients were randomly assigned to standard percutaneous coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points were the occurrence of myocardial blush grade > or =2 and the rate of 90-min ST-segment resolution >70%. The CE-MRI substudy was performed in 75 patients with anterior STEMI to assess microvascular obstruction and infarct size. RESULTS Myocardial blush grade > or =2 and ST-segment resolution occurred more frequently in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the acute phase, microvascular obstruction extent was significantly lower in the EM-PCI group and at 3 months, infarct size was significantly reduced only in the EM-PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%, log-rank test p = 0.02) was observed at 9 months. CONCLUSIONS Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

Impact of Primary Coronary Angioplasty Delay on Myocardial Salvage, Infarct Size, and Microvascular Damage in Patients With ST-Segment Elevation Myocardial Infarction : Insight From Cardiovascular Magnetic Resonance

OBJECTIVES We investigated the extent and nature of myocardial damage by using cardiovascular magnetic resonance (CMR) in relation to different time-to-reperfusion intervals. BACKGROUND Previous studies evaluating the influence of time to reperfusion on infarct size (IS) and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) have yielded conflicting results. METHODS Seventy patients with STEMI successfully treated with primary percutaneous coronary intervention within 12 h from symptom onset underwent CMR 3 +/- 2 days after hospital admission. Patients were subcategorized into 4 time-to-reperfusion (symptom onset to balloon) quartiles: < or =90 min (group I, n = 19), >90 to 150 min (group II, n = 17), >150 to 360 min (group III, n = 17), and >360 min (group IV, n = 17). T2-weighted short tau inversion recovery and late gadolinium enhancement CMR were used to characterize reversible and irreversible myocardial injury (area at risk and IS, respectively); salvaged myocardium was defined as the normalized difference between extent of T2-weighted short tau inversion recovery and late gadolinium enhancement. RESULTS Shorter time-to-reperfusion (group I) was associated with smaller IS and microvascular obstruction and larger salvaged myocardium. Mean IS progressively increased overtime: 8% (group I), 11.7% (group II), 12.7% (group III), and 17.9% (group IV), p = 0.017; similarly, MVO was larger in patients reperfused later (0.5%, 1.5%, 3.7%, and 6.6%, respectively, p = 0.047). Accordingly, salvaged myocardium markedly decreased when reperfusion occurred >90 min of coronary occlusion (8.5%, 3.2%, 2.4%, and 2.1%, respectively, p = 0.004). CONCLUSIONS In patients with STEMI treated with primary percutaneous coronary intervention, time to reperfusion determines the extent of reversible and irreversible myocardial injury assessed by CMR. In particular, salvaged myocardium is markedly reduced when reperfusion occurs >90 min of coronary occlusion.

Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy A Randomized, Controlled Clinical Trial Using Magnetic Resonance Imaging With Myocardial Tagging

Background— cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy. Methods and Results— Fifty-nine diabetic men (60.3±7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [&sgr;], −12.6±3.1; increased left ventricular [LV] torsion [&thgr;], 18.4±4.6°; and increased ratio of LV mass to volume, 2.1±0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro–B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (&Dgr;&thgr;: sildenafil, −3.89±3.11° versus placebo, 2.13±2.35°; P<0.001) and strain (&Dgr;&sgr;: sildenafil, −3.30±1.86 versus placebo, 1.22±1.84; P<0.001). Sildenafil-induced improvement of LV contraction was accompanied by consistent changes in chamber geometry and performance, with a 6.5±11 improvement in mass-to-volume ratio over placebo (P=0.021). Monocyte chemotactic protein-1 and transforming growth factor-&bgr; were the only markers affected by active treatment (&Dgr;monocyte chemotactic protein-1: −75.30±159.28 pg/mL, P=0.032; &Dgr;transforming growth factor-&bgr;: 5.26±9.67 ng/mL, P=0.009). No changes were found in endothelial function, afterload, or metabolism. Conclusions— The early features of diabetic cardiomyopathy are LV concentric hypertrophy associated with altered myocardial contraction dynamics. Chronic phosphodiesterase type 5 inhibition, at this stage, has an antiremodeling effect, resulting in improved cardiac kinetics and circulating markers. This effect is independent of any other vasodilatory or endothelial effects and is apparently exerted through a direct intramyocardial action. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00692237.

Detection of colorectal lesions with virtual computed tomographic colonography

BACKGROUND The aim of our study was to compare the performance of virtual computed tomographic colonography with that of conventional colonoscopy in a blinded, prospective study in 165 patients with suspected colorectal lesions. METHODS There were 165 patients, all referred for conventional colonoscopy, who underwent preliminary virtual computed tomographic colonography. Computed tomograhic images of all suspected lesions were analyzed and subsequently compared with conventional colonoscopy findings. RESULTS There were 30 colorectal cancers and 37 polyps identified at conventional colonoscopy. Virtual computed tomographic colonography correctly detected all cancers, as well as 11 of 12 polyps of 10 mm in diameter or larger (sensitivity, 92%); 14 of 17 polyps between 6 and 9 mm (sensitivity, 82%); and 4 of 8 polyps of 5 mm or smaller (sensitivity, 50%). The per-patient sensitivity and specificity were 92% and 97%, respectively. CONCLUSIONS Virtual computed tomographic colonography has a diagnostic sensitivity similar to that of conventional colonoscopy for the detection of colorectal lesions larger than 6 mm in diameter.

Relationship between location and size of myocardial infarction and their reciprocal influences on post-infarction left ventricular remodelling

AIMS To assess the intricate relationship between myocardial infarction (MI) location and size and their reciprocal influences on post-infarction left ventricular (LV) remodelling. METHODS AND RESULTS A cohort of 260 reperfused ST-segment elevation MI patients was prospectively studied with cardiovascular magnetic resonance at 1 week (baseline) and 4 months (follow-up). Area at risk (AAR) and MI size were quantified by T2-weighted and late-gadolinium enhancement imaging, respectively. Adverse LV remodelling was defined as an increase in LV end-systolic volume ≥15% at follow-up. One hundred and twenty-seven (49%) patients had anterior MI and 133 (51%) patients had non-anterior MI. Although the degree of myocardial salvage was similar between groups (P = 0.74), anterior MI patients had larger AAR and MI size than non-anterior MI patients yielding worse regional and global LV function at baseline and follow-up. At univariable analysis, anterior MI was associated with increased risk of adverse LV remodelling (P = 0.017) and lower LV ejection fraction (EF) at follow-up (P = 0.001), but not when accounted for baseline MI size. Accordingly, at multivariable analysis, baseline MI size but not its location was an independent predictor of adverse LV remodelling (odds ratio = 1.061, P < 0.001) and EF at follow-up (β-coefficient = -0.255, P < 0.001). CONCLUSION Anterior MI patients experience more pronounced post-infarction LV remodelling and dysfunction than non-anterior MI patients due to a greater magnitude of irreversible ischaemic LV damage without any independent contribution of MI location.

Right Ventricular Ischemic Injury in Patients With Acute ST-Segment Elevation Myocardial Infarction. Characterization With Cardiovascular Magnetic Resonance

Background— Experimental data show that the right ventricle (RV) is more resistant to ischemia than the left ventricle. To date, limited data are available in humans because of the difficulty of discriminating reversible from irreversible ischemic damage. We sought to characterize RV ischemic injury in patients with reperfused myocardial infarction using cardiovascular magnetic resonance. Methods and Results— In 3 tertiary centers, 242 consecutive patients with reperfused acute ST-segment elevation myocardial infarction were studied with cardiovascular magnetic resonance at 1 week and 4 months after myocardial infarction. T2-weighted and postcontrast cardiovascular magnetic resonance scans were used to depict myocardial edema and late gadolinium enhancement, respectively. Early after infarction, RV edema was common (51% of patients), often associated with late gadolinium enhancement (31% of patients). Remarkably, RV edema and late gadolinium enhancement were found in 33% and 12% of anterior left ventricular infarcts, respectively. Baseline regional and global RV functions were inversely related to the presence and extent of RV edema and RV late gadolinium enhancement. At follow-up, a significant decrease in frequency (25/242 patients; 10%) and extent of RV late gadolinium enhancement was observed (P<0.001). With the use of multivariable analysis, the presence of RV edema was an independent predictor of RV global function improvement during follow-up (&bgr;-coefficient=0.221, P=0.003). Conclusions— Early postinfarction RV ischemic injury is common and is characterized by the presence of myocardial edema, late gadolinium enhancement, and functional abnormalities. RV injury is not limited to inferior infarcts but is commonly found in anterior infarcts as well. Cardiovascular magnetic resonance findings suggest reversibility of acute RV dysfunction with limited permanent myocardial damage at 4-month follow-up.

Stool tagging applied in thin-slice multidetector computed tomography colonography.

Objective To compare thin-slice multidetector computed tomography colonography (CTC) that uses stool tagging with colonoscopy. Method One hundred fifty patients scheduled for colonoscopy underwent high-resolution CTC. An iodinated contrast agent was added to the preparation to tag the residual colonic fluid and stool. The effect of fluid tagging was assessed first. Sensitivity and specificity were calculated for two independent readers. In addition, values were recalculated separately for the first and last 75 patients. Results Tagging was optimal in 95.3% of the cases, and reader confidence was high. Sensitivities were 64.1%–66.7% (for the 2 readers) for 5- to 9-mm polyps and 91.7% for larger polyps. The overall specificity was 94.2% and 95%. Sensitivity improved during the study for both 5- to 9-mm polyps (from 54.2%–58.3% to 80%) and polyps larger than 9 mm (from 50% to 100%). Specificity changed nonuniformly. Conclusion The combination of fluid tagging and high-resolution scanning in CTC showed high sensitivity and specificity, especially concerning sensitivity for polyps of 10 mm and larger.

Progression of Coronary Artery Calcification in Renal Transplantation and the Role of Secondary Hyperparathyroidism and Inflammation

BACKGROUND AND OBJECTIVES Transplantation should favorably affect coronary calcification (CAC) progression in dialysis; however, changes in CAC score in the individual patient are not reliably evaluated. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS The authors used special tables of reproducibility limits for each score level to study, by multislice computed tomography and biochemistries, the 2-year changes in CAC in 41 transplant patients (age 48 +/- 13 yr, 25 men, dialysis vintage 4.8 +/- 4.3 yr, underwent transplant 6.2 +/- 5.5 yr prior). Thirty balanced dialysis patients served as controls. RESULTS In the study group, Agatston score was stable, and C-reactive protein decreased, whereas fetuin and osteoprotegerin increased. In the control group, Agatston score increased, parathyroid hormone and phosphate decreased, and inflammation markers were persistently twice as high as in the study group. With regard to individual changes, 12.2% transplant patients worsened, compared with 56.6% of patients in dialysis (P < 0.0001). Patients without calcification at entry showed slower progression in transplantation (8.3%) than in dialysis (44.4%; P < 0.034), and the difference was similar to that observed in cases with CAC (17.6% versus 61.9%; P < 0.007). Discriminant analysis indicated parathyroid hormone, the modality of therapy (dialysis or transplantation), and erythrocyte sedimentation rate as the variables most associated with worsening. CONCLUSIONS Renal transplantation lowers but does not halt CAC progression. Inflammation and hyperparathyroidism are associated with progression in the populations studied.

Serum Levels of Calcification Inhibition Proteins and Coronary Artery Calcium Score: Comparison between Transplantation and Dialysis

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 ± 12 years; 30 males, 21 females; previous D duration 4.8 ± 4.2 years; Tx since 6.6 ± 5.5 years; Cr 1.8 ± 0.6 mg/dl) and in 49 D patients (age 49 ± 14 years; 30 males,19 females; D duration 5.6 ± 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 ± 1,637 vs. 1,311 ± 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: rs = 0.439, p < 0.001, and rs = 0.510, p < 0.0001; D: rs = 0.471, p < 0.001, and rs = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (rs = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (rs = –0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (rm = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (rm = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.