Alberto Foà

Histological and Histometric Characterization of Myocardial Fibrosis in End-Stage Hypertrophic Cardiomyopathy: A Clinical-Pathological Study of 30 Explanted Hearts.

Background—Although noninvasively detected myocardial fibrosis (MF) has clinical implications in hypertrophic cardiomyopathy, the extent, type, and distribution of ventricular MF have never been extensively pathologically characterized. We assessed the overall amount, apex-to-base, circumferential, epicardial–endocardial distribution, pattern, and type of MF in 30 transplanted hearts of end-stage, hypertrophic cardiomyopathy. Methods and Results—Visual and morphometric histological analyses at basal, midventricular, and apical levels were performed. Overall MF ranged from 23.1% to 55.9% (mean=37.3±8.4%). Prevalent types of MF were as follows: replacement in 53.3%, interstitial-perimyocyte in 13.3%, and mixed in 33.3%. Considering left ventricular base-to-apex distribution, MF was 31.9%, 43%, and 46.2% at basal, midventricular, and apical level, respectively (P<0.001). Circumferential distributions (mean percentage of MF within the section) were as follows: anterior 11.9%, anterolateral 15.8%, inferolateral 7.0%, inferior 24.3%, anteroseptal 11%, midseptal 10.7%, and posteroseptal 11.4%; circumferential distributions for anterior and inferior right ventricular walls were 3.4% and 4.5%, respectively. Epicardial–endocardial distributions were as follows: trabecular 26.1% and subendocardial 20.2%, midwall 33.4%, and subepicardial 20.3%. Main patterns identified were as follows: midwall in 33.3% of the hearts, transmural in 23.3%, midwall–subepicardial in 23.3%, and midwall-subendocardial in 20%. Conclusions—In end-stage, hypertrophic cardiomyopathy patients undergoing transplantation, more than one-third of the left ventricular myocardium was replaced by fibrosis, mainly of replacement type. MF preferentially involved the left ventricular apex and the midwall. Inferior and anterior walls and septum were maximally involved, whereas inferolateral and right ventricular were usually spared. These observations reflect the complex pathophysiology of hypertrophic cardiomyopathy and may provide clues for the timely recognition of disease progression by imaging techniques capable of quantifying MF.

Redefining the histopathologic profile of acute aortic syndromes: Clinical and prognostic implications

Objectives The study objectives were to describe the aortic histopathologic substrates in patients with type A surgically treated acute aortic syndromes, to provide clinico‐pathological correlations, and to identify the possible prognostic role of histology. Methods We assessed the aortic wall degenerative or inflammatory alterations of 158 patients according to the histopathologic consensus documents. Moreover, we correlated these histologic patterns with the patients’ clinical data and long‐term follow‐up for mortality, major aorta‐related events, and nonaorta‐related events (including cardiovascular ones). Results We identified 2 histopathologic patterns: 122 patients (77%) with degenerative alterations and 36 patients (23%) with mixed degenerative‐atherosclerotic lesions. Patients with mixed alterations were older (mean 69.6 ± 8.7 years vs 62.2 ± 12.4 years, P = .001) and more hypercholesterolemic (33.3% vs 13.9%, P = .017). The degenerative subgroup showed more intralamellar‐mucoid extracellular matrix accumulation (86% vs 66.7%, P = .017) and a lower prevalence of translamellar collagen increase (9.8% vs 50%, P < .001). Patients with mixed degenerative‐atherosclerotic abnormalities more frequently had long‐term nonaorta‐related events compared with those with degenerative abnormalities alone (P = .046); no differences were found between the groups with respect to mortality, major aorta‐related events, and cardiovascular nonaorta‐related events. Conclusions Although degenerative lesions of the medial layer were present in all specimens, substantial atherosclerosis coexisted in approximately one quarter of cases. Patients with mixed degenerative‐atherosclerotic abnormalities had a coherent clinical risk profile, a clinical presentation frequently mimicking acute coronary syndrome, and a higher incidence of nonaorta‐related events during follow‐up. Histopathologic characterization may improve the long‐term prognostic stratification of patients after surgical treatment.

Cardiac pathologic findings in 3 unusual cases of sudden cardiac death related to anorexiant drugs

Amphetamine congeners can be prescribed as anorexiant drugs despite their potential adverse effects, including cardiac toxicity. However, the morphologic features of cardiac damage related to protracted use of these compounds are unknown. We provide a detailed description of cardiac autopsy findings in 3 cases of sudden death associated with protracted use of high doses of phendimetrazine and/or phenylpropanolamine or bupropion prescribed as anorexiants, in association with other compounds. The main cardiac findings were similar in all 3 cases: (1) mild-moderate hypertrophy of the left ventricle and/or the septum; (2) myocardial nonischemic scarring (midmural and/or subepicardial) appearing as discrete foci or with a bandlike morphology; (3) mild-moderate intramural small vessel disease in the absence of significant epicardial coronary artery stenosis; and (4) acute/recent inflammatory lesions consistent with toxic myocarditis. In summary, the detailed pathology examination of the heart in these 3 cases revealed myocardial lesions identical to those reported in catecholamine myocardial damage in all their various stages of evolution. In the presence of a clinical history of long-term intake of anorexiants of this category, it is most important at autopsy to recognize and correctly interpret the acute and chronic myocardial lesions of the type herein described because they represent an anatomical substrate for arrhythmic death.

Donor Selection Criteria: Clinical and Pathological Insights

As donor and donor organ characteristics affect all solid organ recipient outcomes, careful evaluation is essential. In heart transplantation, further aspects are also crucial: donor age (and the last 10 years have seen a notable increase in mean donor age) and potentially negative effects on the heart of brain-death pathophysiologic consequences in brain-dead donors. It is becoming increasingly clear that donor parameters are a major factor in post-transplant mortality, as much as recipient characteristics. Consequently the decision as to whether to accept a heart comes at the end of a complex process.

Long-term Follow up of Patients with Acute Aortic Syndromes: Relevance of both Aortic and Non-aortic Events

BACKGROUND The aim was to assess the long-term outcome of patients diagnosed with type A and type B acute aortic syndromes (AAS) and the mortality risk predictors. METHODS A single centre retrospective observational study was performed on consecutive patients diagnosed with AAS and discharged between 2000 and 2016: 242 surgically treated type A, 87 uncomplicated, medically treated type B, and 80 complicated type B who received endovascular/surgical/hybrid treatment. Follow up of discharged patients (5 ± 3.9 years) was almost complete by the end of the study (December 2017). RESULTS The mean age was 65.3 ± 12.5 years, and 70.2% were men. Long-term all cause mortality was 5.4 per 100 patients per year in surgically treated type A AAS patients and 6.7 per 100 patients per year in type B AAS patients (p = .236). The rates of major aorta related events were 6.1 per 100 patients per year and 13.4 per 100 patients per year, respectively (p < .001). Non-aorta related events during long-term follow up occurred in 18.2 per 100 patients per year in type A and 13.8 per 100 patients per year in type B (p = .055). At the end of follow up 279/409 (68.2%) patients (165/242 type A and 114/167 type B) experienced at least one event. CONCLUSIONS Among patients with either type A or type B AAS surviving the acute phase, the risk of adverse aorta and non-aorta related events, including death, persists during follow up, so that eventually two thirds of patients will experience at least one event. Notably, all cause mortality after type B AAS exceeds that of type A AAS after three years.

Primary Cardiac Leiomyoma Causing Right Ventricular Obstruction and Tricuspid Regurgitation

We report the unique case of a primary cardiac leiomyoma originating from the right ventricle and involving the tricuspid valve in a 43-year-old woman. Echocardiography showed a giant mass causing severe pulmonary stenosis and tricuspid valve regurgitation. The patient underwent surgical excision and histologic examination revealed a primary cardiac leiomyoma. To the best of our knowledge only three cases of primary cardiac leiomyoma have so far been reported, and this is the first case of primary cardiac leiomyoma involving the tricuspid valve apparatus.

Histological and Histometric Characterization of Myocardial Fibrosis in End-Stage Hypertrophic CardiomyopathyCLINICAL PERSPECTIVE

Background—Although noninvasively detected myocardial fibrosis (MF) has clinical implications in hypertrophic cardiomyopathy, the extent, type, and distribution of ventricular MF have never been extensively pathologically characterized. We assessed the overall amount, apex-to-base, circumferential, epicardial–endocardial distribution, pattern, and type of MF in 30 transplanted hearts of end-stage, hypertrophic cardiomyopathy. Methods and Results—Visual and morphometric histological analyses at basal, midventricular, and apical levels were performed. Overall MF ranged from 23.1% to 55.9% (mean=37.3±8.4%). Prevalent types of MF were as follows: replacement in 53.3%, interstitial-perimyocyte in 13.3%, and mixed in 33.3%. Considering left ventricular base-to-apex distribution, MF was 31.9%, 43%, and 46.2% at basal, midventricular, and apical level, respectively (P<0.001). Circumferential distributions (mean percentage of MF within the section) were as follows: anterior 11.9%, anterolateral 15.8%, inferolateral 7.0%, inferior 24.3%, anteroseptal 11%, midseptal 10.7%, and posteroseptal 11.4%; circumferential distributions for anterior and inferior right ventricular walls were 3.4% and 4.5%, respectively. Epicardial–endocardial distributions were as follows: trabecular 26.1% and subendocardial 20.2%, midwall 33.4%, and subepicardial 20.3%. Main patterns identified were as follows: midwall in 33.3% of the hearts, transmural in 23.3%, midwall–subepicardial in 23.3%, and midwall-subendocardial in 20%. Conclusions—In end-stage, hypertrophic cardiomyopathy patients undergoing transplantation, more than one-third of the left ventricular myocardium was replaced by fibrosis, mainly of replacement type. MF preferentially involved the left ventricular apex and the midwall. Inferior and anterior walls and septum were maximally involved, whereas inferolateral and right ventricular were usually spared. These observations reflect the complex pathophysiology of hypertrophic cardiomyopathy and may provide clues for the timely recognition of disease progression by imaging techniques capable of quantifying MF.

Histological and Histometric Characterization of Myocardial Fibrosis in End-Stage Hypertrophic CardiomyopathyCLINICAL PERSPECTIVE: A Clinical-Pathological Study of 30 Explanted Hearts

Background—Although noninvasively detected myocardial fibrosis (MF) has clinical implications in hypertrophic cardiomyopathy, the extent, type, and distribution of ventricular MF have never been extensively pathologically characterized. We assessed the overall amount, apex-to-base, circumferential, epicardial–endocardial distribution, pattern, and type of MF in 30 transplanted hearts of end-stage, hypertrophic cardiomyopathy. Methods and Results—Visual and morphometric histological analyses at basal, midventricular, and apical levels were performed. Overall MF ranged from 23.1% to 55.9% (mean=37.3±8.4%). Prevalent types of MF were as follows: replacement in 53.3%, interstitial-perimyocyte in 13.3%, and mixed in 33.3%. Considering left ventricular base-to-apex distribution, MF was 31.9%, 43%, and 46.2% at basal, midventricular, and apical level, respectively (P<0.001). Circumferential distributions (mean percentage of MF within the section) were as follows: anterior 11.9%, anterolateral 15.8%, inferolateral 7.0%, inferior 24.3%, anteroseptal 11%, midseptal 10.7%, and posteroseptal 11.4%; circumferential distributions for anterior and inferior right ventricular walls were 3.4% and 4.5%, respectively. Epicardial–endocardial distributions were as follows: trabecular 26.1% and subendocardial 20.2%, midwall 33.4%, and subepicardial 20.3%. Main patterns identified were as follows: midwall in 33.3% of the hearts, transmural in 23.3%, midwall–subepicardial in 23.3%, and midwall-subendocardial in 20%. Conclusions—In end-stage, hypertrophic cardiomyopathy patients undergoing transplantation, more than one-third of the left ventricular myocardium was replaced by fibrosis, mainly of replacement type. MF preferentially involved the left ventricular apex and the midwall. Inferior and anterior walls and septum were maximally involved, whereas inferolateral and right ventricular were usually spared. These observations reflect the complex pathophysiology of hypertrophic cardiomyopathy and may provide clues for the timely recognition of disease progression by imaging techniques capable of quantifying MF.