Pitfalls in arrhythmogenic left ventricular cardiomyopathy (ALVC). A review of the literature with considerations on a single case of sudden death in a juvenile athlete.

Sudden cardiac death (SCD) in young athletes represents a challenging issue in forensic practice. The pathologist is frequently asked to establish the cause of death basing upon anatomical findings and to evaluate the role of the physician in preparticipation evaluation (PPE) and eligibility decision. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of SCD during sport activity. However, in the last few years, forms with predominant or even isolated involvement of the left ventricle (LV) have progressively been correlated with a high risk of SCD. We present a case of SCD in an apparently healthy 19-year-old semi-professional football player. Annual PPEs performed in accordance with international and Italian recommendations, were unremarkable. At autopsy, a 1-cm area of subepicardial fibro-fatty replacement was observed at the postero-lateral wall of the LV. The finding was diagnostic of arrhythmogenic left ventricular cardiomyopathy (ALVC). A review of this rare pathology has been performed under a forensic perspective, focusing on the evaluation of the medico-legal responsibility of the physician in the PPE and on the morphological aspects of the disease. Current diagnostic criteria and recommendations result to be focused on the right ventricular pattern, with a risk of misdiagnosis for isolated LV forms. Furthermore, few detailed autopsies cases concerning ALVC have been published. There is a need, therefore, to study this rare disease with a careful and revised approach.

Predictors of mortality in hospital survivors with type 2 diabetes mellitus and acute coronary syndromes.

AIM: To define the predictors of long-term mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome. METHODS AND RESULTS: A total of 7226 patients from a randomized trial, testing the effect on cardiovascular outcomes of the dual peroxisome proliferator-activated receptor agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2 years. The independent mortality predictors were defined using Cox regression analysis. The predictive information provided by each variable was calculated as percent of total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular death contributing for 73% of mortality. The mortality prediction model included N-terminal proB-type natriuretic peptide (adjusted hazard ratio = 1.68; 95% confidence interval = 1.51-1.88; 27% of prediction), lack of coronary revascularization (hazard ratio = 2.28; 95% confidence interval = 1.77-2.93; 18% of prediction), age (hazard ratio = 1.04; 95% confidence interval = 1.02-1.05; 15% of prediction), heart rate (hazard ratio = 1.02; 95% confidence interval = 1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio = 1.11; 95% confidence interval = 1.03-1.19; 8% of prediction), haemoglobin (hazard ratio = 1.01; 95% confidence interval = 1.00-1.02; 8% of prediction), prior coronary artery bypass (hazard ratio = 1.61; 95% confidence interval = 1.11-2.32; 7% of prediction) and prior myocardial infarction (hazard ratio = 1.40; 95% confidence interval = 1.05-1.87; 6% of prediction). CONCLUSION: In patients with type 2 diabetes mellitus and recent acute coronary syndrome, mortality prediction is largely dominated by markers of cardiac, rather than metabolic, dysfunction.

Right Ventricular Strain and Dyssynchrony Assessment in Arrhythmogenic Right Ventricular Cardiomyopathy: Cardiac Magnetic Resonance Feature-Tracking Study.

BACKGROUND: Analysis of right ventricular (RV) regional dysfunction by cardiac magnetic resonance (CMR) imaging in arrhythmogenic RV cardiomyopathy (ARVC) may be inadequate because of the complex contraction pattern of the RV. Aim of this study was to determine the use of RV strain and dyssynchrony assessment in ARVC using feature-tracking CMR analysis. METHODS AND RESULTS: Thirty-two consecutive patients with ARVC referred to CMR imaging were included. Thirty-two patients with idiopathic RV outflow tract arrhythmias and 32 control subjects, matched for age and sex to the ARVC group, were included for comparison purpose. CMR imaging was performed to assess biventricular function; feature-tracking analysis was applied to the cine CMR images to assess regional and global longitudinal, circumferential, and radial RV strains and RV dyssynchrony (defined as the SD of the time-to-peak strain of the RV segments). RV global longitudinal strain (-17±5% versus -26±6% versus -29±6%; P<0.001), global circumferential strain (-9±4% versus -12±4% versus -13±5%; P=0.001), and global radial strain (18 [12-26]% versus 22 [15-32]% versus 27 [20-39]%; P=0.015) were significantly lower and SD of the time-to-peak RV strain in all 3 directions were significantly higher among patients with ARVC compared with patients with RV outflow tract arrhythmias and controls. RV global longitudinal strain >-23.2%, SD of the time-to-peak RV longitudinal strain >113.1 ms, and SD of the time-to-peak RV circumferential strain >177.1 ms allowed correct identification of 88%, 75%, and 63% of ARVC patients with no or only minor CMR criteria for ARVC diagnosis. CONCLUSIONS: Strain analysis by feature-tracking CMR helps to objectively quantify global and regional RV dysfunction and RV dyssynchrony in patients with ARVC and provides incremental value over conventional cine CMR imaging.

Systolic and diastolic myocardial mechanics in hypertrophic cardiomyopathy and their link to the extent of hypertrophy, replacement fibrosis and interstitial fibrosis.

Aim of the present study was to investigate the relations between myocardial mechanics and the extent of hypertrophy and fibrosis in hypertrophic cardiomyopathy (HCM). Forty-five consecutive patients with HCM and 15 subjects without structural heart disease were included. Cardiac magnetic resonance with late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular function, LV mass index and presence/extent of LGE, expression of replacement fibrosis. Myocardial T1 relaxation, a surrogate of interstitial fibrosis, was measured from Look-Locker sequence. Feature-tracking analysis was applied to LV basal, mid and apical short-axis images to assess systolic and diastolic global LV circumferential strain (CS) and strain rate (CSr). Peak systolic CS and CSr were significantly higher among HCM patients as compared to control subjects (p = 0.015 and p = 0.007, respectively). The ratio of peak CSr during early filling to peak systolic CSr was significantly lower among HCM patients (p = 0.002). At multivariate linear regression analysis, LV mass index (p < 0.001) and %LV LGE (p = 0.011) were significantly and independently related to peak systolic CS; LV mass index (p < 0.001) and %LV LGE (p = 0.023) were significantly and independently related to peak systolic CSr; %LV LGE (p = 0.021) and T1 ratio (p = 0.006) were significantly and independently related to the ratio of peak CSr during early filling to peak systolic CSr. LV systolic mechanics are enhanced and LV diastolic mechanics are impaired in HCM. Extent of hypertrophy and replacement fibrosis influence the LV systolic mechanics while extent of replacement fibrosis and interstitial fibrosis influence the LV diastolic mechanics.

Disease-specific differences of left ventricular rotational mechanics between cardiac amyloidosis and hypertrophic cardiomyopathy.

Left ventricular (LV) twist (LVT) and untwisting (LVUT) rate are global and thorough parameters of LV function. The aim of the present study was to investigate the differences in LV rotational mechanics between patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM). Twenty consecutive patients with CA, 20 consecutive patients with HCM, and 20 consecutive subjects without evidence of structural heart disease were included. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular function, LV mass index, and presence/extent of LGE. Feature-tracking analysis was applied to LV basal and apical short-axis images to determine peak LVT, time to peak LVT, peak LVUT rate, and time to peak LVUT rate. Peak LVT and peak LVUT rate were significantly impaired in patients with CA compared with controls (P < 0.05 for both). In patients with HCM, peak LVT was increased (P < 0.05) compared with controls, whereas peak LVUT rate was preserved (P > 0.05). Time to peak LVUT rate was significantly prolonged in patients with CA and in patients with HCM compared with controls (ANOVA P < 0.001). At multivariate analysis, age (P = 0.007), LV ejection fraction (P = 0.035) and extent of LGE (P < 0.001) were independently related to peak LVT, and LV mass index (P = 0.015) and extent of LGE (P = 0.004) were independently related to peak LVUT rate, whereas extent of LGE (P < 0.001) was the only variable independently related to time to peak LVUT rate. In conclusion, CA and HCM have specific behavior of LV rotational mechanics. The extent of LGE significantly influences the LV rotational mechanics.

Predictive value of electrocardiogram in diagnosing acute coronary artery lesions among patients with out-of-hospital-cardiac-arrest.

AIMS: Acute coronary lesions are known to be the most common trigger of out of hospital cardiac arrest (OHCA). Aim of the present study was to assess the predictive value of ST-segment changes in diagnosing the presence of acute coronary lesions among OHCA patients METHODS: Findings of coronary angiography (CA) performed in patients resuscitated from OCHA were retrospectively reviewed and related to ST-segment changes on post-ROSC electrocardiogram (ECG) RESULTS: Ninety-one patients underwent CA after OHCA; 44% of patients had ST-segment elevation and 56% of patients had other ECG patterns on post-ROSC ECG. Significant coronary artery disease (CAD) was found in 86% of patients; CAD was observed in 98% of patients with ST-segment elevation and in 77% of patients with other ECG patterns on post-ROSC ECG (p=0.004). Acute or presumed recent coronary artery lesions were diagnosed in 56% of patients, respectively in 85% of patients with ST-segment elevation and in 33% of patients with other ECG patterns (p<0.001). ST-segment analysis on post-ROSC ECG has a good positive predictive value but a low negative predictive value in diagnosing the presence of acute or presumed recent coronary artery lesions (85% and 67%, respectively) CONCLUSIONS: Electrocardiographic findings after OHCA should not be considered as strict selection criteria for performing emergent CA in patients resuscitated from OHCA without obvious extra-cardiac cause; even in the absence of ST-segment elevation on post-ROSC ECG, acute culprit coronary lesions may be present and considered the trigger of cardiac arrest.

Evaluation of in-stent restenosis in the APPROACH trial (Assessment on the Prevention of Progression by Rosiglitazone On Atherosclerosis in diabetes patients with Cardiovascular History).

To determine (1) the medium-term effect of rosiglitazone and glipizide on intra-stent neointima hyperplasia, (2) restenosis pattern as assessed by intra-vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) in patients with T2DM and coronary artery disease. A total of 462 patients with T2DM were randomized to rosiglitazone or glipizide for up to 18 months in the APPROACH trial, and had evaluable baseline and follow-up IVUS examinations. There was no significant difference in the size of plaque behind stent between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (-5.6 mm(3) vs. 1.9 mm(3); P = 0.61) or with a drug-eluting stent (12.1 mm(3) vs. 5.5 mm(3); P = 0.09). Similarly, there was no significant difference in percentage intimal hyperplasia volume between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (24.1% vs. 19.8%; P = 0.38) or with a drug-eluting stent (9.8% vs. 8.3%; P = 0.57). QCA data (intra-stent late loss, intra-stent diameter stenosis or binary restenosis) were not different between the rosiglitazone and glipizide groups. This study suggests that both rosiglitazone and glipizide have a similar effect on neointimal growth at medium term follow-up, a finding that warrants investigation in dedicated randomized trials.

Long-term outcome after drug-eluting stent implantation in unselected population: ROME and UDINE experience (the RUDI registry).

OBJECTIVES: The aim of our study is to evaluate the safety and efficacy of DES implantation in an unselected, "real world," high-risk population. BACKGROUND: Several clinical trials showed that drug-eluting stents (DESs) implantation is safe and effective in selected population. In spite of these encouraging results, there are some concerns about "real world" utilization of these stents. METHODS: One thousand four hundred and fifty-five off-label patients have been included in our registry. Primary end-points were: long-term clinical incidence of major adverse cardiac and cerebrovascular events (MACCE) and thrombosis (ST). We detected the difference between uniDES vs. multiDES implantation in terms of MACCE, death, nonfatal-MI, the composite of death/nonfatal-MI and target lesion revascularization (TLR) and the difference between DES type in term of MACCE. RESULTS: At 36 months follow-up we found: cardiac death occurred in 20 patients (1.6%); 33 patients (2.6%) had a nonfatal MI and 81 patients (6.3%) had a TLR. We observed one (0.1%) acute, 9 subacute (0.6%), 6 late (0.6%), and 1 (0.5%) very late definite ST. No difference were found in terms of overall MACCE, MI, death and composite of death/nonfatal-MI between uni- and multiDES implantation but multiDES group had a higher incidence of TLR. No difference between DES type in term of MACCE was detected. CONCLUSIONS: DES utilization shows their safety and efficacy in off-label patients with complex clinical and angiographic profile in terms of long-term incidence of MACCE. MultiDES implantation is associated with a higher risk of long-term TLR. No difference between DES type was found.

Radionuclide evidence for reversible ischemia after percutaneous treatment of anomalous right coronary artery with dynamic compression by great vessels.

Anomalous origin of the right coronary artery from the left sinus is a rare congenital anomaly, possibly related to myocardial ischemia by dynamic compression. We present a case of percutaneous treatment of this coronary anomaly resulting in regression of inducible ischemia, as demonstrated by radionuclide scintigraphy.

Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial.

AIMS: In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary endpoint (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. METHODS AND RESULTS: Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event. Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46-0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25-0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71-0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). CONCLUSION: While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS.

Transient left ventricular apical ballooning syndrome: a 4-year experience.

BACKGROUND: Transient left ventricular apical ballooning syndrome, primarily described in Japanese patients, has been recently recognized outside Japan also. Aim of this study is to elucidate incidence and clinical features of left ventricular apical ballooning syndrome in a tertiary-care hospital in northeastern Italy. METHODS AND RESULTS: From January 2002 to August 2006, 29 patients admitted for suspected acute coronary syndrome (25 women, mean age 64+/-12 years) fulfilled the Mayo Clinic Criteria of left ventricular apical ballooning syndrome. Twenty patients (69%) had an episode of emotional or physiologic stress preceding left ventricular apical ballooning syndrome. Fourteen patients (48%) had at least one risk factor for coronary artery disease. Chest pain was present at admission in 24 patients (83%). Twenty-five patients (86%) had ST-T segment abnormalities at ECG on admission. Four patients were treated with fibrinolytic therapy and one with glycoprotein IIb/IIIa inhibitors. At coronary angiography, 23 patients (79%) had no coronary lesions, 2 (7%) had small vessel occlusion and 4 (14%) had nonsignificant coronary stenosis. ECG changes and echocardiographic wall motion abnormalities completely regressed in all patients within 10 weeks. Neither death nor major complications occurred during in-hospital stay and after discharge. Two patients (7%) experienced a recurrence during follow-up. CONCLUSION: Left ventricular apical ballooning syndrome is a novel syndrome with a nonnegligible incidence, a clinical presentation mimicking acute myocardial infarction and a favorable outcome. The present data confirm a higher prevalence in women and the frequent association with emotional stress. The differential diagnosis with acute myocardial infarction at presentation is still puzzling, and only ECG findings in conjunction with echocardiography and coronary angiography are so far diagnostics.

The effect of fellows' training in invasive cardiology on radiological exposure of patients.

The aim of this work was to evaluate and quantify the impact of an invasive training of cardiology fellows on some exposure parameters. From 1 January 2000 to 31 December 2002, three staff members performed 2.582 diagnostic procedures (Group 1) that were compared with 819 performed by, or with the participation of five cardiology fellows (Group 2). Exposure parameters were as follows (Group 1/Group 2): fluoroscopy time 3.8 +/- 4.5/5.5 +/- 5.9 min (+38%), mean number of frames 589 +/- 282/642 +/- 260 (+9%), Kerma-area product (KAP) during fluoroscopy 10.6 +/- 14/15.5 +/- 16 Gycm2 (+45%), KAP during cine-angiography 20.8 +/- 14/22.5 +/- 12 (+8%), total KAP 31.5 +/- 28/38.1 +/- 28 (+21%). Differences were all significant (P

Patient-prosthesis mismatch after small-size stentless aortic valve replacement.

OBJECTIVE: The aim of this study was to determine the occurrence of patient-prosthesis mismatch (P-PM) after aortic valve replacement (AVR) with a small-size Cryolife O'Brien (CLOB) bioprosthesis and to evaluate its clinical and hemodynamic implications. METHODS: Sixty-two patients (mean age 70.9 +/- 5.2 years, 77.8% females), receiving a labeled 21-23 mm CLOB between 1993 and 2000, were retrospectively studied. Effective orifice area (EOA) was calculated by the continuity equation and then indexed to the patient's body surface area (BSA) to obtain the indexed EOA (EOAI). Based on previous observations a mismatch was defined as EOAI or= 0.8 cm/m2 showed an earlier concentric remodeling up to 1 year; no difference was demonstrated at later studies between groups. Survival and clinical status results were not affected by an EOAI

Sixteen-year results of composite aortic root replacement for non-dissecting chronic aortic aneurysms.

BACKGROUND: The aim of this study was to evaluate the early and long-term outcomes in patients undergoing a Bentall procedure or its button modification for chronic aortic aneurysms with aortic valve incompetence. METHODS: Between January 1986 and January 2002, 65 patients (84% males, mean age 58.9 +/- 11 years) underwent aortic root replacement with a Bentall or a button-Bentall operation. Annuloaortic ectasia was the most frequent cause of aortic disease in this series (n = 37, 56.9%), followed by atherosclerotic aneurysms (n = 22, 33.9%), and post-stenotic dilation (n = 5, 7.7%). One patient (1.5%) underwent redo aortic root replacement,3 (4.6%) had a Marfan syndrome, and 6 (9.2%) underwent a concomitant replacement of the aortic arch. The duration of follow-up ranged from 2 to 192 months (mean 89.6 +/- 21.8 months). RESULTS: The 30-day mortality was 0%. Early non-fatal complications comprised: bleeding requiring surgical re-exploration (n = 1, 1.5%), low output syndrome (n = 1, 1.5%), acute renal insufficiency (n = 1, 1.5%), transient ischemic attack (n = 2, 3.1%), stroke (n = 1, 1.5%), and pulmonary insufficiency (n = 1, 1.5%). There was a late death due to a pulmonary neoplasm. The 16-year actuarial survival was 97 +/- 2% (hazard 0.02 +/- 0.02). No patient required reoperation. Furthermore, the long-term clinical follow-up was characterized by the complete absence of endocarditis, anticoagulant-related hemorrhage, valve thrombosis, and prosthetic failure. Finally, the NYHA functional status was significantly improved (1.1 +/- 0.50, p < 0.001 vs preoperatively). CONCLUSIONS: The late results of the Bentall and button-Bentall procedures were excellent. Our findings confirm that these techniques still constitute the gold standard in the surgical treatment of combined valve and ascending aorta pathologies.

Long-term results of Bentall composite aortic root replacement for ascending aortic aneurysms and dissections.

STUDY OBJECTIVES: The aim of this study was to evaluate the early and long-term outcomes in patients undergoing aortic root replacement (ARR) with the Bentall procedure. DESIGN: Retrospective study. SETTING: Cardiothoracic surgery unit. PATIENTS AND METHODS: Between January 1986 and January 2002, 72 patients (mean age 58.3 +/- 12.4 years, 81.9% males) underwent ARR by means of a Bentall operation. Annuloaortic ectasia was the most frequent cause of aortic disease in this series of patients (31 patients; 43.1%), followed by type A dissection (19 patients; 26.3%), atherosclerotic aneurysm (18 patients; 25.1%), and poststenotic dilatation (4 patients; 5.5%). Nine patients (12.5%) had Marfan syndrome, and 10 patients (13.8%) underwent a concomitant replacement of the aortic arch. Follow-up ranged from 2 to 192 months (mean [+/- SD], 86.6 +/- 23.8 months). RESULTS: The mean 30-day mortality rate was 5.5 +/- 2%. The mean early mortality rate was 21 +/- 4% and 0% (p < 0.001), respectively, in patients with and without dissecting aortic aneurysms. There were two late deaths that were due to a pulmonary neoplasm and a cerebrovascular accident. The mean 16-year survival rate was 91.7 +/- 3.2%. The mean hazard of freedom from death was constant beyond 3 years (8.5 +/- 3.5%). No patient required reoperation. Furthermore, the long-term clinical follow-up was marked by a complete absence of endocarditis, anticoagulant-related hemorrhage, valve thrombosis, and prosthesis failure. Finally, patients showed a significant improvement in mean New York Heart Association functional status (1.3 +/- 0.1; p < 0.001 [postoperatively vs preoperatively]). CONCLUSIONS: In our experience, the late results of the Bentall operation were satisfactory. Our findings confirm that this technique still represents the procedure of choice for ARR with coronary reimplantation.

Early in vivo hemodynamic results after aortic valve replacement with the St Jude Medical Regent mechanical heart valve in patients with pure aortic stenosis.

BACKGROUND: The St Jude Medical Regent is a new-generation mechanical heart valve that represents a design evolution of the St Jude Hemodynamic Plus Series (HP). The purpose of this study was to evaluate early "in vivo" hemodynamic performance of the Regent valve in patients with aortic stenosis. METHODS: Between March 2000 and December 2001, 32 patients (mean age 59.9 +/- 5.9,56.3% male) with pure aortic stenosis received a Regent mechanical prosthesis in the aortic position. Hemodynamic performance was assessed by Doppler echocardiography at discharge, two months, six months, and one year by calculating peak transprosthetic velocity (Vmax), mean (MG) and peak (PG) transprosthetic gradients, effective orifice area index (EOAI), left ventricular mass index (LVMI), and degree of aortic regurgitation. RESULTS: A significant reduction in mean and peak transaortic gradients (p < 0.001) and a significant increase in EOAI (p < 0.001) over time followed valve replacement, and a bivariate analysis of variance (ANOVA) failed to demonstrate statistical differences by valve size over time (p = ns). A significant reduction in left ventricular hypertrophy occurred over time (p < 0.001) in all valve sizes (p = ns between groups): baseline LVMI was 221 +/- 57 g/cm2; it decreased by 30 g/cm2 (p < 0.001) at discharge. LVMI decreased from 191 +/- 54 g/cm2 to 161 +/- 41 g/cm2 (p < 0.001) from discharge to two months. Further reductions were not significant. At the six-month follow-up no patient in our cohort exhibited moderate or severe aortic regurgitation at Doppler echocardiography. CONCLUSIONS: Early results with the St Jude Medical Regent valve have been satisfactory. Further assessments are necessary to confirm these results.