Ferdinando Pasquale

Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction

Objectives: To investigate diagnostic routes, echocardiographic substrates, outcomes and prognostic factors in patients with isolated ventricular non-compaction (IVNC) identified by echocardiographic laboratories with referral from specialists and primary care physicians. Patients and design: Since 1991, all patients with suspected IVNC were flagged and followed up on dedicated databases. Patients were divided into symptom-based and non-symptom-based diagnostic subgroups. Results: 65 eligible patients were followed up for 6–193 months (mean 46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%) LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was characterised by younger age, lower prevalence of ECG abnormalities, better systolic function and lower left atrial size, whereas the extent of non-compaction was not different. No major cardiovascular events occurred in the non-symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients experienced cardiovascular death or heart transplantation (p  =  0.01, Kaplan–Meier analysis). Independent predictors of cardiovascular death or heart transplantation were New York Heart Association class III–IV, sustained ventricular arrhythmias and left atrial size. Conclusions: IVNC is associated with a broad spectrum of clinical and pathophysiological findings, and the overall natural history and prognosis may be better than previously thought. Adult patients with incidental or familial discovery of IVNC have an encouraging outlook, whereas those who have symptoms of heart failure, a history of sustained ventricular tachycardia or an enlarged left atrium have an unstable course and more severe prognosis.

New pathological insights into cardiac amyloidosis: implications for non-invasive diagnosis.

Background: Knowledge of the patterns of myocardial amyloid accumulation could improve the interpretation of electrocardiographic, echocardiographic and magnetic resonance imaging findings of amyloidosis. We assessed the extent and pattern of myocardial amyloid infiltration in explanted or autopsied hearts of patients with cardiomyopathy related to acquired monoclonal immunoglobulin light-chain (AL) or hereditary transthyretin (TTR) related amyloidosis (ATTR). Methods: We analyzed nine explanted/autopsied hearts from patients with AL (n = 4) and ATTR (n = 5) cardiac amyloidosis. For each heart, a biventricular histological macrosection was obtained at mid-ventricular level and analyzed with both inspective and computer-assisted histologic and histomorphometric analysis aimed in particular at quantifying muscle cells, fibrosis and amyloid infiltration. Results: The extent of amyloid infiltration of the left ventricle (LV) ranged from 45 to 76% (median [interquartile range (IQR)] = 57% [51–64]) of the overall surface. Although LV trabecular and subendocardial were the most infiltrated layers (45–94%, median [IQR] = 73% [67–84] and from 44 to 71%, median [IQR] = 57% [49–59], respectively), intra- and inter-patient heterogeneity was high. Three main patterns of amyloid infiltration of the LV were identified: diffuse (five cases), mainly subendocardial (two cases), and mainly segmental (two cases). The extent of amyloid infiltration of the right ventricle ranged from 48 to 93% (median [IQR] = 61% [59–83]); contributions of parietal and trabecular layers ranged from 32 to 99% (median [IQR] = 63% [47–88]) and from 49 to 93% (median [IQR] = 74% [64–79]), respectively. Conclusions: In amyloidotic cardiomyopathy, amyloid deposition is highly heterogeneous. Different patterns of infiltration are identifiable, including diffuse, mainly segmental and mainly subendocardial. Awareness of this variability can help the interpretation of ECGs, echocardiograms and magnetic resonance imaging.

Effects of myocardial fibrosis assessed by MRI on dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective database analysis

Background While implications of myocardial fibrosis on left ventricular (LV) function at rest have been studied in hypertrophic cardiomyopathy (HCM), the pathophysiological consequences on dynamic LV outflow tract (LVOT) gradient have so far not been investigated in detail. Objective To evaluate the influence of myocardial fibrosis, detected by MRI as late-gadolinium enhancement (LGE), on LVOT gradient in HCM. Design Retrospective database analysis. Setting A single Italian cardiomyopathies referral centre. Patients Seventy-six HCM patients with normal ejection fraction at rest. Interventions Patients underwent cardiac MR and performed bicycle exercise echocardiogram within a month. Results LGE was present in 54 patients (71%), ranging from 0.2% to 32.4% of LV mass. There was a weak correlation between the amount of fibrosis and LVOT gradient variation during exercise in the overall population (r=−0.243, p=0.034) and a stronger correlation in patients with obstructive HCM at rest (r=−0.524, p=0.021). Patients with an LVOT gradient increase ≥50 mm Hg during exercise had a significantly lesser extent of fibrosis than those with an increase <50 mm Hg (0.7% (IQR 0–2.4) vs 3.2% (IQR 0.2–7.4), p=0.006). The extent of fibrosis was significantly lower among the highest quartiles of LVOT gradient increase (p=0.009). Conclusions In patients with HCM and normal ejection fraction at rest, myocardial fibrosis was associated with a lower increase in LVOT gradient during exercise, probably due to a lesser degree of myocardial contractility recruitment. This negative association was more evident in patients with an obstructive form at rest.

Troponin T elevation in acute aortic syndromes: Frequency and impact on diagnostic delay and misdiagnosis

Aims: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS. Methods and results: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05–3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12–5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86–3.10, p = 0.131). Conclusions: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

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.

Acute heart failure in patients with acute aortic syndrome: pathophysiology and clinical–prognostic implications

Although acute heart failure (AHF) is a potential complication of acute aortic syndromes (AAS), its clinical details and management implications have been scarcely evaluated. This study aimed to assess prevalence, pathophysiological mechanisms, impact on treatment, and in‐hospital mortality of AHF in AAS.

Clinical Use of Doppler Echocardiography in Organic Mitral Regurgitation: From Diagnosis to Patients' Management

Knowledge of mitral regurgitation (MR) is essential for any care provider, and not only for those directly involved in the management of cardiovascular diseases. This happens because MR is the most frequent valvular lesion in North America and the second most common form of valve disease requiring surgery in Europe. Furthermore, due to the ageing of the general population and the reduced mortality from acute cardiovascular events, the prevalence of MR is expected to increase further. Doppler echocardiography is essential both for the diagnosis and the clinical management of MR. In the present article, we sought to provide a practical step-by-step approach to help either performing a Doppler echocardiography or interpreting its findings in light of contemporary knowledge on organic (but not only) MR.

Inferior Q waves in apparently healthy subjects: Should we take a deep breath? An electrocardiographic, echocardiographic and cardiac magnetic resonance study

AIM To evaluate the diagnostic accuracy of electrocardiographic inferior Q waves persistence during inspiration and echocardiographic segmental wall motion abnormalities for the detection of previously unsuspected silent myocardial infarction, by using cardiac magnetic resonance as the gold standard. METHODS We prospectively enrolled 50 apparently healthy subjects with inferior Q waves on routine electrocardiogram and high atherosclerotic risk profile. Patients underwent electrocardiogram during deep inspiration, standard transthoracic echocardiography, and cardiac magnetic resonance. RESULTS Inferior Q waves during deep inspiration persisted in 10 subjects (20%) and cardiac magnetic resonance was positive in 10 (20%). Between the 10 positive cardiac magnetic resonance subjects 8 showed persistence of inferior Q waves, giving a sensitivity of 80% (95%;CI 44.4-97.5%) and a specificity of 95% (95%;CI 83.1-99.4%). Segmental wall motion abnormalities were present overall in 10 subjects (20%), but only in 5 of the 10 positive cardiac magnetic resonance subjects, giving a sensitivity of 87.5% (95% CI 73.2-95.8) and specificity of 50% (95% CI 18.7-81.3). CONCLUSIONS Electrocardiographic inferior Q waves persistence during deep inspiration is a simple test with a high accuracy for diagnosis of silent myocardial infarction. Standard echocardiography resulted less accurate.

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.