The ventricular ectopic QRS interval (VEQSI): Diagnosis of arrhythmogenic right ventricular cardiomyopathy in patients with incomplete disease expression.

BACKGROUND: The ventricular ectopic QRS interval (VEQSI) has been shown to identify structural heart disease and predict mortality. In arrhythmogenic right ventricular cardiomyopathy (ARVC), early diagnosis is difficult using current methods, and life-threatening arrhythmias are common and difficult to predict. OBJECTIVE: The purpose of this study was to assess the utility of ventricular ectopic indices including VEQSI in ARVC diagnosis. METHODS: We studied 70 patients with ARVC [30 with definite disease (age 47 ± 12 years; 60% male), 40 with incomplete disease expression (age 44 ± 18 years; 44% male)], 116 healthy controls (age 40 ± 15 years; 56% male), and 26 patients with normal heart right ventricular outflow tract (RVOT) ectopy (age 46 ± 17 years; 27% male). The duration of the broadest ventricular ectopic beat during 12-lead Holter monitoring was recorded as VEQSI max. RESULTS: VEQSI max was associated with age and gender, but not with conducted QRS duration. Adjusted VEQSI max was greater in ARVC patients than in control groups. In healthy males (44.5 years), estimated VEQSI max was 163 ms (95% confidence interval [CI] 159-167 ms); in definite ARVC 212 ms (95% CI 206-217 ms); in incompletely expressed ARVC 204 ms (95% CI 199-210 ms); and in normal heart RVOT ectopy 171 ms (95% CI 165-178 ms). VEQSI max >180 ms had 98% sensitivity and specificity for diagnosis of ARVC (area under the curve 0.99, 95% CI 0.980-0.998). In our incompletely expressed ARVC patients, VEQSI max >180 ms identified 88% as affected. CONCLUSION: VEQSI max distinguishes ARVC patients, including those with incomplete disease expression, from healthy controls and patients with normal heart RVOT ectopy.

Efficacy of weekly docetaxel in locally advanced cardiac angiosarcoma.

BACKGROUND: Primary cardiac angiosarcoma is extremely aggressive; however, it is often misdiagnosed because of its rarity. For locally advanced tumors, doxorubicin-based chemotherapy regimens are the standard of treatment, even if the gain in term of progression-free survival is limited and is no longer than 5 months. CASE PRESENTATION: We report the case of a Caucasian 23-year-old man with locally advanced cardiac angiosarcoma who underwent radical surgical resection after a prolonged response to weekly docetaxel and complementary radiotherapy. CONCLUSION: Combined treatment with weekly docetaxel and radiotherapy may be a valid alternative for the treatment of locally advanced cardiac angiosarcoma; the combination can lead to radical surgical resections, avoiding the cumulative cardiotoxicity of antracycline-based regimens.

[Consensus document on endomyocardial biopsy of the Associazione per la Patologia Cardiovascolare Italiana]. / Documento di consenso sulla biopsia endomiocardica promosso dall'Associazione per la Patologia Cardiovascolare Italiana.

The Italian Scientific Associations of Cardiologists and Cardiovascular Pathologists have produced this consensus document on the diagnostic role of endomyocardial biopsy (EMB) in terms of techniques, analysis and reporting. The document is intended for clinical cardiologists, hemodynamic experts, electrophysiologists, surgical pathologists, and cardiac surgeons. It has three main aims: a) to collocate EMB in the context of currently available tools for diagnosis of heart diseases; b) to provide recommendations for rational implementation; c) to outline key characteristics (standards) for Italian cardiology and surgical pathology centers that perform and analyze EMB. A general lack of prospective, controlled studies addressing EMB prohibited the use of traditional evidence-based recommendations that rely on classes of available evidence. Thus, it was agreed that three key points should be taken into account: a) the specific pathology to be diagnosed (or excluded); b) the existence of any alternative, non-invasive diagnostic techniques; c) the overall consequences of reaching a definite diagnosis on patients' clinical management. Accordingly, we propose recommendations for EMB based on the following levels of diagnostic value: level 1: no alternative method exists to reach a definite diagnosis that can have obvious consequences for clinical management; level 2a: no alternative method exists to reach a definite diagnosis; however, the implications for clinical management are uncertain; level 2b: no alternative method exists to reach a definite diagnosis; however, the diagnosis would not influence clinical management; level 3: an alternative method exists to reach a definite diagnosis. The second part of the document proposes current protocols for the preparation, analysis and reporting of EMB in the context of each main pathologic entity. Particular attention is given to tissue characterization and implementation of molecular tests.

Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types.

BACKGROUND: Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis. METHODS AND RESULTS: We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1+/-0.5 versus 0.9+/-0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events. CONCLUSIONS: AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.

Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study.

BACKGROUND: Folic acid therapy reduces homocysteine plasma levels, which seem to influence occurrence of cardiac allograft vasculopathy, but its effect on medium- or long-term prognosis after heart transplantation is unknown. METHODS: We analyzed 7-year outcome of 51 recipients randomized to receive 15 mg/day of methyltertrahydrofolate for 1 year after heart transplantation or standard therapy alone (originally, for intravascular ultrasound study of short-term cardiac allograft vasculopathy progression); recipients were observed for a further 5 to 6 years. RESULTS: Overall, 13 deaths occurred (six oncologic, five cardiovascular, two infective). Estimated 7-year survival was better in recipients randomized to folate (88%+/-6% vs. 61%+/-9%, P=0.04). After adjusting for age, pretransplant coronary artery disease, and hyperhomocysteinemia, posttransplant folic acid therapy was associated with lower mortality (relative risk [RR] 0.53, 95% confidence interval [CI] 0.25-0.97; P=0.036), apparently driven by reductions in both cancer-related and cardiovascular causes. Reduced mortality was marked in a high-risk subgroup comprising older recipients and patients transplanted because of coronary artery disease (RR 0.43, 95% CI 0.17-0.85) but not in the lower-risk subgroup (RR 1.11, 95% CI 0.22-5.61). CONCLUSIONS: Although further studies are needed, it seems reasonable to suggest folate therapy to heart transplant recipients. It is possible that properties other than homocysteine reduction may provide antitumoral benefits.

Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure.

BACKGROUND: It is unknown whether time-related changes of pulmonary hypertension (PH) have prognostic relevance in severe chronic heart failure (CHF). METHODS: All CHF patients referred for follow-up from 1996 through 2003 were screened for this study. Eligibility depended on availability of a concomitant clinical, laboratory, electrocardiographic (ECG), echocardiographic and right-heart catheterization (RHC) assessment at index evaluation, as well as absence of pre-capillary PH. RESULTS: One hundred ninety-six patients (age 54 +/- 9 years; 27% women, 73% men; 50% in New York Heart Association [NYHA] Class III or IV) were included. PH at index evaluation was an independent predictor of acute heart failure or cardiovascular death (AHF/CD), with adjusted risk ratio (RR) = 2.30, 95% confidence interval (CI) 1.42 to 3.73 and p < 0.001. A pre-study (> or =6 months) RHC was available for 174 of the 196 patients. Worsening of mean pulmonary artery pressure (mPAP) of > or =30% (a pre-specified cut-off corresponding to the 75th percentile of DeltamPAP%) provided prognostic information independent of all index-evaluation parameters (adjusted RR = 2.60, 95% CI 1.45 to 4.67, p = 0.001), and from time-related changes in the other hemodynamic parameters (p < or = 0.033). CONCLUSIONS: PH retains independent prognostic significance even after adjusting for a large set of clinical/laboratory/instrumental parameters. Furthermore, serial measurements of mPAP seem to provide additional prognostic information as compared with a single assessment. These findings indicate that serial evaluations of PAP may help identify a sub-set of high-risk CHF patients deserving a particularly close follow-up to facilitate timely indications for non-pharmacologic strategies, including (when appropriate) heart transplantation.

Dilated-hypokinetic evolution of hypertrophic cardiomyopathy: prevalence, incidence, risk factors, and prognostic implications in pediatric and adult patients.

OBJECTIVES: This study sought to investigate the incidence, risk factors, and prognosis of dilated-hypokinetic evolution in a large cohort of patients with hypertrophic cardiomyopathy (HCM) followed up at a cardiology center serving both the pediatric and the adult population. BACKGROUND: The available data on this evolution of HCM mainly regards prevalence (rather than incidence) in adults, with very little being known about the pediatric population. METHODS: A total of 222 consecutive HCM patients (65% men, 19% < or =18 years old) were prospectively evaluated for a mean follow-up of 11 +/- 9 years. RESULTS: A diagnosis of dilated-hypokinetic HCM was made in 12 patients at first evaluation (11 without previous septal myectomy surgery; prevalence, 4.9%). Twelve of the 210 patients with classic HCM at first evaluation underwent dilated-hypokinetic evolution (incidence, 5.3/1,000 patient-years). Patients with prevalent/incident dilated-hypokinetic evolution were younger at first evaluation (32 +/- 14 years vs. 41 +/- 21 years, p = 0.04) and more often had a family history of HCM (61% vs. 26%, p = 0.002) or sudden death (43% vs. 19%, p = 0.01) with respect to patients who maintained classic HCM. Moreover, they showed greater interventricular septum (23 +/- 3 mm vs. 19 +/- 6 mm, p = 0.004) and posterior wall (15 +/- 3 mm vs. 13 +/- 4 mm, p = 0.006) thickness. Cardiovascular death-free survival was lower among patients with dilated-hypokinetic HCM (p < 0.04). Cox proportional hazards regression analysis identified left ventricular wall thickness (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 1.01 to 1.14; p = 0.03) and end-diastolic diameter (HR = 1.08; 95% CI 1.04 to 1.11; p = 0.0001) as independent predictors of cardiovascular death. CONCLUSIONS: Dilated-hypokinetic evolution is rare but not exceptional in HCM. Young age at diagnosis, family history of HCM, and greater wall thickness are incremental risk factors for dilated-hypokinetic HCM, which carries an ominous prognosis.

[Clinical problems in heart transplant recipients]. / I problemi clinici del cardiopatico trapiantato.

Heart transplantation has become a more and more effective therapeutic strategy in severe heart failure patients. An opportune management of the several medical, immunological and psychological complications, that may occur during heart transplant recipients' life, is mandatory to succeed in this therapeutic approach. Indeed, thanks to heart transplantation, recipients may recover from a lethal cardiovascular disease, but on the other hand, they may encounter several co-morbidities. An optimized management has to involve not only the referring Transplant Center, but also the single patient's personal cardiologist and general physician. Therefore, the present paper has the educational aim to present the most common clinical problems occurring during heart transplant recipients' follow-up, by reviewing current literature in the light of the experience gained by the Bologna Heart Transplant Unit.