Giovanni Fazio

Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations

There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy‐proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima‐media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014‐1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043‐4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0‐F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3‐F4 fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). Conclusion: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients. (HEPATOLOGY 2012)

Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction.

Heat shock proteins (Hsps) are produced in response to various stressors, including ischemia-reperfusion, and they can exit cells and reach the blood. In this pilot study, we determined serum levels of Hsp60 and heme-oxygenase-1 (HO-1; also named Hsp32) in subjects with acute myocardial infarction (AMI) to assess their clinical significance and potential prognostic value. We also performed a bioinformatics analysis of the 2 molecules in search of structural clues on the mechanism of their release from cells. We studied 40 patients consecutively admitted for AMI (male:female patient ratio=20:20, mean age: 64 ± 13 years) and 40 matched controls. A blood sample was drawn for biochemical analyses within 24 h of symptoms onset, and Hsp60 and HO-1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). All patients were followed up for 6 months to register adverse post-AMI cardiovascular events. A multivariate analysis demonstrated that elevated Hsp60 (P=0.0361), creatine phosphokinase-muscle brain (CK-MB) (P=0.0446), and troponin (P=0.0490) were predictive of post-AMI adverse events. In contrast, increased HO-1 showed a significant association with less severity of coronary artery diseases (P=0.0223). These findings suggest that Hsp60 and HO-1 play distinct roles in the pathogenesis of AMI and subsequent AMI-related pathology. The possibility that these proteins differ in their roles and mechanisms of action in AMI and post-AMI pathology was supported also by the bioinformatics estimates of probability of their localization in various subcellular compartments. The results clear the way for subsequent investigation on the pathogenetic role and clinical significance of Hsp60 and HO-1 in AMI.

Ventricular Tachycardia in Non-Compaction of Left Ventricle: Is This a Frequent Complication?

Background: Isolated left ventricular non‐compaction is the result of incomplete myocardial morphogenesis, leading to persistence of the embryonic myocardium. The condition is recognized by an excessively prominent trabecular meshwork and deep intertrabecular recesses of the left ventricle. Whether these intertrabecular recesses are a favorable substrate for ventricular arrhythmias is unclear. Some reports have found that the fatal ventricular arrhythmias may occur in approximately half of the patients. In this report we investigated about this association.

The role of the renin-angiotensin system in atrial fibrillation and the therapeutic effects of ACE-Is and ARBS

Atrial fibrillation (AF) is the most common rhythm disturbance in medical practice and represents a very expensive health problem. AF can be managed with the prevention of thromboembolism and either a rate control of rhythm strategy. As both strategies have important limitations, probably a preventative strategy in patients at risk of developing arrhythmia can be a more attractive option. The renin-angiotensin system (RAS) seems to be involved in the genesis of arrhythmia by the following two mechanisms: 1. the induction of atrial fibrosis and structural remodelling by mitogen-activated protein kinase (MAPK) expression and reduction of collagenase activity; 2. the induction of electrical remodelling by shortening of the atrial effective refractory period (AERP) and of the action potential duration. For these reasons it has been hypothesized that angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II receptor blockers (ARBs) may play a role in preventing AF recurrence. The aim of the present review was to analyse evidence supporting the usefulness of RAS inhibition in patients with AF in order to focus on which specific subset of patients it would most favour. After reviewing the literature, we conclude that, although many studies and meta-analysis have supported the advantage of RAS block in preventing AF recurrence, it is premature to recommend the use of ACE-Is and ARBs specifically for the prevention of AF. However we believe that as these drugs are safe and manageable, they should be considered the drugs of choice in patients with AF and coexisting clinical conditions such as hypertension, coronary disease, heart failure and diabetes mellitus.

The noncompaction of the left ventricular myocardium: our paediatric experience.

Objectives The noncompaction of the left ventricular myocardium is a rare congenital heart disease, characterized by an excessive prominence of trabecular meshwork, spaced out by deep intertrabecular recesses, consequent to the arrest of the normal myocardium embryogenesis. Although there are numerous descriptions, the physiopathological effects of the structural alterations, just like the clinical spectrum and the evolution of the disease, are not totally clarified. In the present study, we have evaluated the natural history of the disease, the familial incidence and the alterations of the systolic and diastolic function. Methods We collected a series of 21 young patients who were affected by noncompaction of left ventricular myocardium. In all cases, a diagnosis was echocardiographically made on the basis of a reported spongy/compacted ratio > 2 in one or more segments of the left ventricle. Thirteen patients were male and eight were female, with a mean age of 12.7 years (range 21 days to 27 years). The average follow-up time was 7.8 years (range 1–18 years); all patients were periodically tested by ECG Holter and two-dimensional and Doppler echocardiogram. In 14 patients, the last echocardiographic evaluation included the analysis of tissue Doppler imaging (TDI). Results The noncompaction of left ventricular myocardium was isolated in nine cases and associated with a structural cardiopathy in 12 cases: with atrial septal defect in four cases, ventricular septal defect in four cases, aortopulmonary window in one case, aortic coarctation in one case and bicuspid aortic valve in one case. One case presented a type Kent ventricular pre-excitation. Twelve cases were symptomatic at the moment of the diagnosis (for heart failure in 11 cases and for syncope in one case). Nine cases were asymptomatic and the diagnosis was made during a family screening or occasionally. In ten of the 11 subjects affected by congestive heart failure, medical therapy re-established a good haemodynamic balance (in two cases, it was possible to suspend the therapy). In one case with congestive heart failure and pulmonary hypertension in New York Heart Association class III, we recommended heart transplantation. We did not find any dysrhythmia in any of the cases. Diastolic function impairment, tested by transmitral blood pressure monitoring and TDI, was found in seven of 14 patients, all with reduced left ventricular contractility. Conclusions We noticed a considerable variability of clinical presentation in our cases, according to the number of the ventricular segments affected by the anomaly. According to our data, middle-term prognosis appears to be better than that previously reported in the literature. We found a reduction of the systolic function only in 50% of cases, all with severe involvement of the apical and postero-lateral segments. Diastolic function was compromised only in those patients with severe impairment of systolic function.

Impact of ‘‘Off-Label’’ Use of Ivabradine on Exercise Capacity, Gas Exchange, Functional Class, Quality of Life, and Neurohormonal Modulation in Patients With Ischemic Chronic Heart Failure

Background: Epidemiologic studies indicate that elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients (pts) with chronic heart failure (CHF). Clinical trials with β-blockers suggest that HR reduction is an important mechanism of their benefit in pts with stable CHF. Pharmacologic inhibition of the If current now provides the opportunity of pure HR reduction. The purpose of this study was to evaluate the impact of ‘‘Off-Label’’ use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in pts with ischemic CHF. Methods: Between January 2008 and June 2008, a graded maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85% of the peak VO2 at the baseline and after 3 months were performed, and at the same times, N-terminal probrain natriuretic peptide (NT-proBNP) levels were also measured, in 60 pts (45 M, 15 F, mean age 52.7 ± 5.3 years), with stable ischemic CHF, New York Heart Association (NYHA) functional classes II (n = 35)—III (n = 25), with left ventricular ejection fraction (LVEF) ≤ 40%, randomized to a ‘‘off-label’’ ivabradine use (n = 30) and a control group (n = 30). Results: The exercise capacity increased from 14.8 ± 2.5 to 28.2 ± 3.5 min (P < .0001) and the peak oxygen consumption tended to improve from 13.5 ± 1.3 to 17.9 ± 2.4 mL/kg per minute (P < .0001) in ivabradine group. Oxygen consumption at the anaerobic threshold (AT) increased from 11.9 ± 1.4 to 15.3 ± 1.4 mL/kg per minute (P < .0001). NTproBNP levels decreased from 2356 ± 2113 pg/mL to 1434 ± 1273 pg/mL (P = .045). No significant differences were found in control group at 3 months. The positive ivabradine effects were also associated with an improvement in the NYHA functional class and quality of life. Conclusion: The ‘‘Off-Label’’ use of ivabradine significantly improves the exercise capacity, gas exchange, functional heart failure class, quality of life, and neurohormonal modulation in pts with ischemic CHF.

Cardiopulmonary Exercise Testing in Patients with Chronic Heart Failure: Prognostic Comparison from Peak VO2 and VE/VCO2 Slope.

Background: Cardiopulmonary exercise testing with ventilatory expired gas analysis (CPET) has proven to be a valuable tool for assessing patients with chronic heart failure (CHF). The maximal oxygen uptake (peak V02) is used in risk stratification of patients with CHF. The minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) has recently demonstrated prognostic significance in patients with CHF. Methods: Between January 2006 and December 2007 we performed CPET in 184 pts (146 M, 38 F, mean age 59.8 ± 12.9 years), with stable CHF (96 coronary artery disease, 88 dilated cardiomyopathy), in NYHA functional class II (n.107) - III (n.77), with left ventricular ejection fraction (LVEF) ≤ 45%,. The ability of peak VO2 and VE/VCO2 slope to predict cardiac related mortality and cardiac related hospitalization within 12 months after evaluation was examined. Results: Peak VO2 and VE/VCO2 slope were demonstrated with univariate Cox regression analysis both to be significant predictor of cardiac-related mortality and hospitalization (p < 0.0001, respectively). Non survivors had a lower peak VO2 (10.49 ± 1.70 ml/kg/min vs. 14.41 ± 3.02 ml/kg/min, p < 0.0001), and steeper Ve/VCO2 slope (41.80 ± 8.07 vs. 29.84 ± 6.47, p < 0.0001) than survivors. Multivariate survival analysis revealed that VE/VCO2 slope added additional value to VO2 peak as an independent prognostic factor (χ2: 56.48, relative risk: 1.08, 95% CI: 1.03 – 1.13, p = 0.001). The results from Kaplan-Meier analysis revealed a 1-year cardiac-related mortality of 75% in patients with VE/VCO2 slope ≥ 35.6 and 25% in those with VE/VCO2 slope < 35.6 (log rank χ2: 67.03, p < 0.0001) and 66% in patients with peak VO2 ≤ 12.2 ml/kg/min and 34% in those with peak VO2 > 12.2 ml/kg/min (log rank χ2: 50.98, p < 0.0001). One-year cardiac-related hospitalization was 77% in patients with VE/VCO2 slope ≥ 32.5 and 23% in those with VE/VCO2 slope < 32.5 (log rank χ2: 133.80, p < 0.0001) and 63% in patients with peak VO2 ≤ 12.3 ml/kg/min and 37% in those with peak VO2 > 12.3 ml/kg/min (log rank χ2: 72.86, p < 0.0001). The VE/VCO2 slope was demonstrated with receiver operating characteristic curve analysis to be equivalent to peak VO2 in predicting cardiac-related mortality (0.89 vs. 0.89). Although area under the receiver operating characteristic curve for the VE/VCO2 slope was greater than peak VO2 in predicting cardiac-related hospitalization (0.88 vs 0.82), the difference was no statistically significant (p = 0.13). Conclusion: These results add to the present body of knowledge supporting the use of CPET in CHF patients. The VE/VCO2 slope, as an index of ventilatory response to exercise, is an excellent prognostic parameter and improves the risk stratification of CHF patients. It is easier to obtain than parameters of maximal exercise capacity and is of equivalent prognostic importance than peak VO2.

Neuromuscular Disorders in Left Ventricular Hypertrabeculation/Noncompaction

Left ventricular hypertrabeculation / noncompaction (LVHT) is in the majority of the cases associated with hereditary cardiac or skeletal muscle disease or with chromosomal abnormalities. Depending on the study more than two thirds of the LVHT patients also present with a neuromuscular disorder (NMD). NMDs most frequently associated with LVHT are the Barth syndrome, mitochondrial disorders, zaspopathy, and myotonic dystrophies. NMDs only occasionally presenting with LVHT are the dystrobrevinopathy, laminopathies, dystrophinopathies, myoadenylat-deaminase deficiency, hereditary inclusion body myositis and the hereditary neuropathy CMT1A. A causal relation between NMDs and LVHT is likely, although the exact relationship and pathomechanic association remains elusive. The close pathogenetic relation is supported by the fact that the phenomenon of acquired LVHT occurs predominantly in NMDs. Consequent referral of LVHT patients to the neurologist, consequent referral of NMD patients to the cardiologist, and family investigations may help and to elucidate unsolved issues concerning the pathogenesis, course and prognosis of LVHT.

Clinical findings of Takotsubo cardiomyopathy: results from a multicenter international study.

Background Takotsubo cardiomyopathy consists of reversible systolic left ventricular apical ballooning associated with chest pain. Electrocardiographic abnormalities and the minimal rise of serum cardiac markers are similar to those in acute myocardial infarction, but without evidence of myocardial ischemia or injury. To date, many reports concerning this kind of acute reversible heart failure have been published, but the information available about the management of affected patients is scarce and the clinical data are incomplete. Aims In the present study, we report a collection of 40 patients who were affected by Takotsubo cardiomyopathy obtained in a multicentric international study, aiming to investigate the origins, and the clinical and instrumental patterns, and to establish the best diagnostic criteria for this syndrome. Methods and Results In the analysed group, the mean age was 68 years, of whom 85% were women. On admission to hospital, 68% of patients reported chest pain. An electrocardiogram (ECG) showed anterolateral (34%) or anterior (36%) ST segment elevation. The ECG demonstrated hyperkinesis of the basal segments with a severe hypokinesis of the other segments. Mean ejection fraction was 42.53%. Three patients died within the first 24 h from acute heart failure. The remaining 37 patients showed a complete resolution of symptoms and a complete normalization of the kinesis deficiency. Sixteen patients underwent myocardial scintigraphy, nine cases underwent myocardial biopsy and two patients received an ergonovine test. Conclusion Our results demonstrate a good course of Takotsubo cardiomioathy, after the initial phase. An echocardiogram is an important tool for improving the diagnosis.

Magnetic resonance in isolated noncompaction of the ventricular myocardium

UNLABELLED Non-compaction of the ventricular myocardium (LCVM) is a rare disorder of myocardial morphogenesis usually diagnosed in paediatric age. The diagnosis was echocardiographically made on the basis of a reported spongeous/compacted ratio >2 in one or more segments of the left ventricle during the diastolic period. We aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging in distinguishing pathological left ventricular non-compaction. METHODS We collected a consecutive series of 8 patients, 5 males and 3 females, with a mean age of 14.9 years with non-compaction of left ventricular myocardium. All patients were admitted in our divisions of cardiology. In all cases the diagnosis was performed by echocardiography. The diagnosis was obtained when the spongeous/compacted ratio was >2 in one or more segments of left ventricle, evaluated in systolic and diastolic period. In the end we completed the diagnosis by scanning with a Signa HD 1.5 T (GE, Milwaukee, USA) the same 8 patients affected by non compaction of ventricular myocardium. In all patients cardiac-gated T1 and T2 black-blood FSE images in short axis and in four-chamber horizontal long axis were obtained. Breath hold cine MR sequences (FIESTA) were performed, covering the whole left ventricle in short-axis plane and in four-chamber view. A segmented inversion-recovery fast gradient echo sequence (IR-FGE) was performed in the short-axis plane of the LV and in four-chamber-view after Gadolinium injection in 8 patients affected by non compaction of left ventricle. At the end of examination the spongeous/compacted ratio >2 was calculated in all involved segments of the left ventricle in diastole. RESULTS In all cases we demonstrated by echocardiography an involvement of the ventricular apex. In 3 cases the structural alterations involved also lateral wall of left ventricle. Magnetic resonance evaluation showed that involvement demonstrated by the echocardiogram was the same: ventricular apex involved in every patient, lateral wall in 3 and all segments in 2. However the spongeous/compacted ratio was >>2 in all patients, with a mean value of 3,1. CONCLUSIONS Although our data refer to a small population of patients and need further confirmation, they suggest that it seems reasonable increase the cut-off for spongeous/compacted ratio from a value of 2 to 2.5 for non-compaction diagnosis when high-resolution magnetic resonance is used.