Alessandro Manzoli

The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review

The World Health Organization/International Society and Federation of Cardiology (WHO/ISFC) task force on the definition and classification of cardiomyopathies recently updated and reclassified heart muscle diseases.1 Myocarditis was defined as “an inflammatory disease of the myocardium . . . diagnosed by established histological, immunological, and immunohistochemical criteria.” Three distinct forms of inflammatory cardiomyopathy (that is, myocarditis associated with cardiac dysfunction) are recognised: idiopathic, autoimmune, and infectious. Various infectious factors may cause myocarditis, but viral agents, especially coxsackie group B viruses, are most commonly associated with this disease.2 Myocarditis has been recognised for almost two centuries, since Corvisart first described this disease in clinical terms in 1812,3 but in the last three decades there has been renewed interest in the inflammatory process in the myocardium. The reasons for this are multiple: the introduction of endomyocardial biopsy for in vivo diagnosis (the disease was often overdiagnosed in the past on purely clinical grounds)4; related efforts to produce standardised criteria for histological diagnosis (the Dallas criteria; fig 1)5; better understanding of cardiotropic viruses, studied in animal models of myocarditis,6 leading to new insights into the immunological mechanisms of the disease (fig2)7 and potential treatments in humans8; and lastly—and perhaps most interestingly—the finding of a possible causal relation between viral myocarditis and dilated cardiomyopathy,9 a major cause of congestive heart failure in western countries. Figure 1 Histological section of active lymphocytic myocarditis according to the Dallas criteria. A dense infiltrate of lymphocytes in close contact with damaged and necrotic myocytes is evident (haematoxylin and eosin × 100). Figure 2 CD4RO positive T lymphocytic cellular infiltrates in a diffuse pattern (× 40). Despite numerous published reports on this disease, the natural history of acute myocarditis is still poorly understood, despite the development of immunological …

Angiography alone versus angiography plus optical coherence tomography to guide decision-making during percutaneous coronary intervention: the Centro per la Lotta contro l'Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study.

AIMS Angiographic guidance for percutaneous coronary intervention (PCI) has substantial limitations. The superior spatial resolution of optical coherence tomography (OCT) could translate into meaningful clinical benefits. We aimed to compare angiographic guidance alone versus angiographic plus OCT guidance for PCI. METHODS AND RESULTS Patients undergoing PCI with angiographic plus OCT guidance (OCT group) were compared with matched patients undergoing PCI with angiographic only guidance (Angio group) within 30 days. The primary endpoint was the one-year rate of cardiac death or myocardial infarction (MI). A total of 670 patients were included, 335 in the OCT group and 335 in the Angio group. OCT disclosed adverse features requiring further interventions in 34.7%. Unadjusted analyses showed that the OCT group had a significantly lower one-year risk of cardiac death (1.2% vs. 4.5%, p=0.010), cardiac death or MI (6.6% vs. 13.0%, p=0.006), and the composite of cardiac death, MI, or repeat revascularisation (9.6% vs. 14.8%, p=0.044). Angiographic plus OCT guidance was associated with a significantly lower risk of cardiac death or MI even at extensive multivariable analysis adjusting for baseline and procedural differences between the groups (OR=0.49 [0.25-0.96], p=0.037) and at propensity-score adjusted analyses. CONCLUSIONS This observational study, the first ever formally to appraise OCT guidance for PCI decision-making, suggests that the use of OCT can improve clinical outcomes of patients undergoing PCI.

Stenting of Culprit Lesions in Unstable Angina Leads to a Marked Reduction in Plaque Burden: A Major Role of Plaque Embolization? A Serial Intravascular Ultrasound Study

Background—Intravascular ultrasound (IVUS) studies have shown that a mechanism of plaque compression/embolization contributes toward the poststenting increase in lumen area. The aim of this IVUS study was to compare the mechanisms of lumen enlargement after coronary stenting in 54 consecutive patients with unstable angina (UA) (group 1) and 56 with stable angina (group 2) to verify whether plaque embolization plays a major role in the former. Methods and Results—Both groups underwent the IVUS assessment (speed, 0.5 mm/sec) before the intervention and after stent implantation. The lumen area, the external elastic membrane area, and the plaque+media area (PA) were measured at 0.5-mm intervals. PA reduction in the lesion site was significantly greater in group 1 (−2.50±1.97 versus −0.53±1.43 mm2, P <0.001). After stenting, 47% of the lumen area increase in group 1 was obtained by means of PA reduction, and 53% was attributable to external elastic membrane area increase; the corresponding figures in group 2 were 13% and 87% (P <0.05). Decrease in PA after stenting was the only significant predictor of the MB fraction of creatinine kinase (CK-MB) release in a multiple regression model (P =0.047). Conclusions—Serial volumetric IVUS assessment revealed in UA lesions a marked poststenting reduction in plaque volume, which is significantly greater than in stable angina and is associated with postprocedural CK-MB release. The decrease in PA during the procedure predicts CK-MB release in a multiple regression model. These findings suggest that stent deployment is often associated with plaque embolization in patients with UA.

Acute effects of nitrates on exercise testing in patients with syndrome X. Clinical and pathophysiological implications.

BackgroundSublingual nitrates are much more effective in relieving angina pectoris in patients with coronary artery disease than in patients with syndrome X, but it is not known whether their effect on exercise tolerance is also different in these two groups of patients. Methods and ResultsTreadmill exercise testing was performed before and after administration of sublingual isosorbide dinitrate (ISDN, 5 mg) in 18 patients with syndrome X (effort angina and normal coronaries, group X) and in 33 patients with documented coronary artery disease (group C). As a selection criterion, all patients had ST- segment depression ≥ 1 mm on the control exercise test. Compared with the control test, the main differences in the two groups observed during the exercise test after administration of ISDN were (1) heart rate at 1-mm ST-segment depression was higher (126 ± 25 versus 104 ± 15 beats per minute [bpm], P < .01) in group C, whereas it was not different (125 ± 15 versus 126 ± 16 beats per minute) in group X; (2) the rate-pressure product at 1-mm ST-segment depression, the time to 1-mm ST-segment depression, and the exercise duration were significantly improved in group C (P < .01 for all) but were worsened in group X (18047 ± 4159 versus 20535 ± 4507 bpm · mm Hg, P = .014; 268 ± 312 versus 429 ± 214 seconds, P < .01; 494 ± 279 versus 622 ± 194 seconds, P = .013, respectively); (3) a normalization of the ECG (no ST-segment depression) was obtained in 10 patients (30%) of group C but in only 1 (5%) of group X (P < .01); (4) angina was prevented in 10 of 19 patients of group C but in no patient of group X (P < .01). ConclusionsIn patients presenting with anginal chest pain, the effects of sublingual nitrates on exercise testing appear to be clinically useful to distinguish patients with coronary artery stenoses from patients with syndrome X. Indeed, worsening of exercise tolerance is highly predictive of normal coronary arteries. Furthermore, the failure of nitrates to improve exercise tolerance in patients with syndrome X suggests that a deficiency in coronary prearteriolar nitric oxide production is unlikely to play a key role in the pathophysiology of the syndrome.

Eccentric atherosclerotic plaques with positive remodelling have a pericardial distribution: a permissive role of epicardial fat?A three-dimensional intravascular ultrasound study of left anterior descending artery lesions

Aims The transversal distribution of coronary atherosclerotic plaques (AP) (myocardial vs pericardial) affects vessel remodelling. The aim of this study was to define the impact of transversal lesion distribution on vessel remodelling in proximal and distal coronary segments using a 3D intravascular ultrasound (IVUS) reconstruction. Methods The study group included 70 lesions located in the left anterior descending artery within 5mm of the septal take-off, and imaged using 3D-IVUS. The take-off of the septal branch was used to divide the plaque into a myocardial and pericardial surface. The IVUS index of vessel remodelling was calculated as: [narrowest external elastic membrane (EEM) site cross-sectional area (CSA)−reference EEM CSA)/reference EEM CSA×100]. The lesions with an intermediate vessel remodelling index (between −25% and +15%) were excluded from analysis. Results Of the 38 APs with a pericardial distribution, 34 (89%) showed positive remodelling \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((P{<}0.001)\) \end{document}. The distal lesions had a positive vessel remodelling index regardless of transversal plaque distribution. At multivariate analysis, pericardial distribution and the distal location of AP were the only independent variables predictive of positive remodelling. Conclusions The transversal distribution of atherosclerotic plaque affects vessel remodelling in left anterior descending coronary lesions, probably because of an extravascular splinting effect. Distal lesions usually show positive remodellingregardless of transversal plaque distribution.

Angiographic and clinical outcome of invasively managed patients with thrombosed coronary bare metal or drug-eluting stents: the OPTIMIST study

AIMS Stent thrombosis (ST) is a major complication of percutaneous coronary interventions (PCIs). An invasive management by re-PCI is the commonly adopted treatment for ST, but data on outcome are limited. METHODS AND RESULTS We performed a 2-year multicentre registry enrolling consecutive patients with angiographically confirmed ST undergoing PCI. The primary angiographic endpoint was optimal angiographic reperfusion (TIMI 3 + blush grade 2 or 3). The primary clinical endpoints were death and major adverse coronary and cerebrovascular events (MACCEs) at 6 months. A total of 110 patients underwent 117 urgent PCI during the study. Patients with drug-eluting stent (DES) thrombosis, compared with those with bare metal stent (BMS) thrombosis, exhibited a higher rate of late or very late presentation and of anti-platelet therapy withdrawal. Optimal angiographic reperfusion was obtained in 64% of the patients. Death and MACCE rates at 6 months were 17 and 30%, respectively. Clinical outcome was similar for BMS and DES thrombosis. Very late ST, implantation of stent during PCI for ST, and failure to achieve optimal angiographic reperfusion were the independent predictors of 6-month mortality. CONCLUSION DES and BMS thromboses have different clinical features, but a similar poor outcome. Indeed, PCI for ST is associated with a low rate of reperfusion and to a high rate of death and MACCE, calling for action in order to prevent its occurrence and to improve its management.

Eccentric atherosclerotic plaques with positive remodeling have a pericardial distribution: A permissive role of epicardial fat—A three-dimensional intravascular ultrasound study of left anterior descending artery lesions

AIMS The transversal distribution of coronary atherosclerotic plaques (AP) (myocardial vs pericardial) affects vessel remodelling. The aim of this study was to define the impact of transversal lesion distribution on vessel remodelling in proximal and distal coronary segments using a 3D intravascular ultrasound (IVUS) reconstruction. METHODS The study group included 70 lesions located in the left anterior descending artery within 5mm of the septal take-off, and imaged using 3D-IVUS. The take-off of the septal branch was used to divide the plaque into a myocardial and pericardial surface. The IVUS index of vessel remodelling was calculated as: [narrowest external elastic membrane (EEM) site cross-sectional area (CSA)-reference EEM CSA)/reference EEM CSAx100]. The lesions with an intermediate vessel remodelling index (between -25% and +15%) were excluded from analysis. RESULTS Of the 38 APs with a pericardial distribution, 34 (89%) showed positive remodelling (P<0.001). The distal lesions had a positive vessel remodelling index regardless of transversal plaque distribution. At multivariate analysis, pericardial distribution and the distal location of AP were the only independent variables predictive of positive remodelling. CONCLUSIONS The transversal distribution of atherosclerotic plaque affects vessel remodelling in left anterior descending coronary lesions, probably because of an extravascular splinting effect. Distal lesions usually show positive remodelling regardless of transversal plaque distribution.

Percutaneous coronary intervention of unprotected left main coronary artery disease as culprit lesion in patients with acute myocardial infarction.

OBJECTIVES This study sought to evaluate short- and long-term outcomes of patients undergoing emergency percutaneous coronary intervention (PCI) for acute myocardial infarction due to a culprit lesion in an unprotected left main coronary artery. METHODS In this retrospective, 2-center, international observational study, 5,261 patients were admitted between February 2005 and December 2008 with acute myocardial infarction and treated with PCI; of these, 1,277 were ST-segment elevation myocardial infarction and 3,984 non-ST-segment elevation myocardial infarction. We identified 48 patients among this cohort who underwent emergency PCI to an unprotected left main coronary artery culprit lesion. RESULTS Mean age was 70 ± 12.5 years, and 45% of the patients presented with ST-segment elevation myocardial infarction or new left bundle branch block. Cardiogenic shock was present in 45%, and distal left main coronary artery disease was present in 71% of patients. Angiographic procedural success was achieved in 92% of patients. Overall in-hospital mortality was 21%, due in all cases to refractory, multiorgan failure. Twenty-five percent experienced major adverse cardiac events, defined as death, myocardial infarction, stent thrombosis, and target vessel revascularization. In patients presenting in cardiogenic shock, in-hospital mortality was 32%. At 1-year follow-up, in-hospital survivors had a mortality rate of 10.5%, whereas 18.4% experienced subsequent major adverse cardiac events. Long-term prognosis was excellent in hospital survivors with a 1-year survival rate of 89.5%. CONCLUSIONS Patients with acute myocardial infarction and thrombosis of the unprotected left main coronary artery are a high-risk subgroup with a substantial mortality, particularly if they present in cardiogenic shock. We demonstrate that in these patients, PCI is a feasible treatment option associated with reasonably good outcomes. Long-term prognosis is excellent in hospital survivors with an 89.5% survival rate at 1 year.

Ischemic-like ST-Segment Changes During Holter Monitoring in Patients With Angina Pectoris and Normal Coronary Arteries But Negative Exercise Testing

To evaluate whether Holter electrocardiographic monitoring may improve the detection of ST-segment depression in patients with anginal chest pain and normal coronary arteries, we performed symptom-limited exercise testing and 24-hour Holter monitoring in a group of 38 such patients (27 women, age 54 +/- 8 years). Patients were divided into 2 groups:group X1 included 28 patients with and group X2 10 patients without significant ST-segment depression during exercise testing. There were no significant differences between the 2 groups in age, gender, characteristics of chest pain, exercise duration, heart rate (HR), and blood pressure at peak exercise, but anginal pain during exercise testing was reported by 10 patients of group X1 (36%) and 9 of group X2 (90%) (p <0.01). Episodes of ST-segment depression on Holter monitoring were found in 17 patients of group X1 (61%) and in 5 patients of group X2 (50%) (p = NS). There were no differences between the 2 groups in daily number of ST episodes (3.6 +/- 4 vs 2.8 +/- 5 episodes per patient), symptomatic episodes (8% vs 18%), and duration of the episodes. On average, HR increased significantly, in a similar way, from 15 minutes before ST-segment depression to 1-mm ST in both groups, and its value at the onset of ischemia was similar in the 2 groups (102 +/- 22 vs 109 +/- 18 beats/min, p = NS). Finally, HR at 1-mm ST during Holter monitoring was significantly lower than that observed at 1-mm ST during exercise testing (127 +/- 16 beats/min, p < or = 0.01) in group X1, and it was also lower than that observed at peak exercise (136 +/- 22 beats/min, p < or = 0.01) in group X2. In conclusion, Holter monitoring can significantly increase the detection of ST-segment depression in patients with anginal pain and normal coronary arteries, indicating a cardiac, although not necessarily ischemic, origin of the pain. Indeed, 50% of our patients with negative symptom-limited exercise testing showed spontaneous ST changes, compatible with transient myocardial ischemia, during daily activities. Differences in the response of coronary microvascular tone to exercise testing and to stimuli operating during daily life are likely to play a significant role in determining these findings.

Early and long-term results of stenting of diffuse coronary artery disease

Diffuse coronary artery disease (CAD) is considered unfavorable for interventional procedures; however, the results of stenting of diffuse CAD have not been completely characterized. We performed stenting in 100 consecutive patients with diffuse CAD, defined as significant stenosis >20 mm (n = 59 patients), multiple significant stenoses in the same artery (n = 23 patients), or significant narrowing involving the whole length of the coronary artery (n = 18 patients). Angiographic success was achieved in 103 arteries (100%) and clinical success was obtained in all 100 patients. There were no deaths; no patient had stent closure, acute myocardial infarction, or required emergency coronary artery bypass surgery. All 100 patients had >6 months follow-up (mean 18 +/- 7 months, range 7 to 31); 77 (77%) remained asymptomatic, and 5 (5%) had acute myocardial infarction, of whom 2 died (2%). In-stent restenosis was observed in 12 patients (12%) and repeat angioplasty was performed in 10. Including those patients who underwent repeat angioplasty, 89 (89%) maintained clinical improvement and 95 (95%) were alive and free of bypass surgery during follow-up. Life-table analysis showed 86% freedom from death, myocardial infarction, and target lesion revascularization at 28 months. Thus, selected patients with diffuse CAD may be treated with satisfactory acute and long-term results by stent implantation.