Clinical profile and predictors of in-hospital outcome in patients with heart failure: the FADOI "CONFINE" Study.

BACKGROUND: Heart failure (HF) is a major health and social problem. Internal Medicine (IM) wards admit a high proportion of patients with HF, frequently with advanced age and comorbidities. Few recent data are available in this setting, especially on predictors of in-hospital outcome. METHODS: In this observational study, we recruited patients admitted with diagnosis of HF and present in five index days, in 91 units of IM in Italy. Characteristics and management of HF, comorbidities, functional and cognitive status, and quality of life, were analyzed. RESULTS: We observed 1411 patients, with a mean age of 78.7 ± 9.6 years. At admission, 81.7% of the patients were in NYHA classes III-IV. Ninety percent of the patients had at least one comorbidity. Dementia or severely impaired functional status were registered in 21.5% and 22.8% of the patients. In 89 patients (6,3%) a negative outcome (death or clinical worsening) occurred during hospitalization. A number of variables were significantly related to negative outcome by means of univariate analysis (systolic blood pressure <100 mm Hg, pulse pressure ≥ 55 mm Hg, anaemia, brain deficit, permanent bed rest, Barthel Index ≤ 30). At multivariable analysis, significant correlation was retained by anaemia and Barthel Index ≤ 30, the latter being the strongest predictor. CONCLUSIONS: Real-world patients with HF and hospitalized in IM are frequently very old, frail and with multiple comorbidities. Functional and cognitive status significantly influence patients' outcome, and this could lead to a rethinking of the overall (in-hospital but also home-based) management of HF.

Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).

Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death. The disease locus was mapped to chromosome 1q42--q43. We report here on the physical mapping of the critical ARVD2 region, exclusion of two candidate genes (actinin 2 and nidogen), elucidation of the genomic structure of the cardiac ryanodine receptor gene (RYR2) and identification of RYR2 mutations in four independent families. In myocardial cells, the RyR2 protein, activated by Ca(2+), induces the release of calcium from the sarcoplasmic reticulum into the cytosol. RyR2 is the cardiac counterpart of RyR1, the skeletal muscle ryanodine receptor, involved in malignant hyperthermia (MH) susceptibility and in central core disease (CCD). The RyR2 mutations detected in the present study occurred in two highly conserved regions, strictly corresponding to those where mutations causing MH or CCD are clustered in the RYR1 gene. The detection of RyR2 mutations causing ARVD2, reported in this paper, opens the way to pre-symptomatic detection of carriers of the disease in childhood, thus enabling early monitoring and treatment.

Clinical profile and long-term follow-up of 37 families with arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: We sought to define the clinical picture and natural history of familial arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease, often familial, clinically characterized by the impending risk of ventricular arrhythmias and sudden death. METHODS: Thirty-seven ARVC families of northeast Italy were studied. Probands had a histologic diagnosis of ARVC, either at autopsy (19 families) or endomyocardial biopsy (18 families). Protocol of the investigation included basal electrocardiogram (ECG), 24-hour ECG, signal-averaged ECG, stress test and two-dimensional Doppler echocardiography. Invasive evaluation was performed when deemed necessary. RESULTS: Of the 365 subjects, 151 (41%) were affected, 157 (43%) were unaffected, 17 (5%) were healthy carriers, and 40 (11%) were uncertain. Mean age at diagnosis was 31+/-13 years. By echocardiography, 64% had mild, 30% had moderate, and 6% had severe form. Forty percent had ventricular arrhythmias, 49 were treated with antiarrhythmic drugs, and two were treated with implantable cardioverter defibrillators. Sport activity was restricted in all. Of the 28 families who underwent linkage analysis, 6 mapped to chromosome 14q23-q24, 4 to 1q42-q43, and 4 to 2q32.1-q32.3. No linkage with known loci was found in four families and 10 had uninformative results. During a follow-up of 8.5+/-4.6 years, one patient died (0.08 patient/year mortality), and 15 developed an overt form of ARVC. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy is a progressive disease appearing during adolescence and early adulthood. Systematic evaluation of family members leads to early identification of ARVC, characterized by a broad clinical spectrum with a favorable outcome. In the setting of positive family history, even minor ECG and echocardiographic abnormalities are diagnostic.

Familial effort polymorphic ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy map to chromosome 1q42-43.

In the present study we report on another cause of an arrhythmia associated with familial arrhythmogenic right ventricular cardiomyopathy (ARVC), which is linked to chromosome 1q42-43. Two families with 48 subjects were studied with 12-lead electrocardiography, 24-hour ambulatory electrocardiography, chest x-ray, M-mode and 2-dimensional echocardiography, signal-averaging electrocardiography, and exercise stress testing. Six subjects also underwent right and left ventricular angiography and electrophysiologic study. An endomyocardial biopsy was performed in 1 subject. The genetic study included pedigree reconstruction and linkage analysis with polymorphic DNA markers. Five young subjects died suddenly during exercise; autopsy was performed in 3 and showed segmental fibro-fatty replacement of the right ventricle, mostly at the apex. Two of them experienced syncopal attacks during effort. Sixteen living subjects, without arrhythmias at rest had polymorphic ventricular arrhythmias during effort; ARVC was diagnosed in 15, whereas 1 did not have any demonstrable cardiac abnormality. The remaining family members were healthy and did not have arrhythmias. The linkage study assigned the disease locus to chromosome 1q42-q43, in close proximity to the alpha-actinin 2 locus (maximal lod score was 5.754 at theta = 0) with a 95% penetrance. Thus, these data suggest that effort-induced polymorphic ventricular arrhythmias and juvenile sudden death can be due to adrenergic stimulation in a particular genetic group of ARVC patients. In these cases the pathology was segmental, mostly localized to the right ventricular apex. Ventricular arrhythmias that are present in these families differ from the monomorphic ones that are usually seen in patients with ARVC.

Arrhythmogenic right ventricular dysplasia: pregnancy under flecainide treatment.

This is the first reported case of a young woman with a moderate to severe form of arrhythmogenic right ventricular dysplasia under flecainide treatment who, with her physician's consent, decided to have a baby. During the pregnancy, antiarrhythmic drug therapy was continued and plasma levels of flecainide were measured via high-performance liquid chromatography. Every three months, she was monitored by means of resting ECG, signal-averaging ECG, 24-hour ECG and echocardiogram. We did not observe any meaningful events. A normal baby was delivered at full term by cesarean section. The baby's Apgar score was 9 after 1 and 5 minutes. The baby had to be fed using artificial milk. In conclusion, no changes in the pathology of the right ventricle were observed, we did not record any arrhythmia and the use of flecainide acetate did not cause any teratogenic effects. Nevertheless, we cannot assign any epidemiologic value to our report.

Surgical anatomy of aorto-left ventricular tunnel.

BACKGROUND: Owing to the rarity of aorto-left ventricular tunnel, surgical experience with this condition is generally limited. The anatomic configuration remains to be clarified in the light of better understanding of the normal aortic root. METHODS: Two autopsied hearts with aorto-left ventricular tunnel were examined and compared with four normal heart specimens. The normal hearts were sectioned in a variety of planes to display the ventriculoarterial junction. RESULTS: The leaflets of the pulmonary valve in both normal and abnormal hearts have semilunar attachments to a sleeve of freestanding ventricular musculature, the infundibulum. An extensive fibrofatty tissue plane then interposes between the freestanding infundibulum and the aortic sinuses. The aorto-left ventricular tunnels in the abnormal hearts pass within this tissue plane. The aortic orifice of the tunnel is distal to the level of the sinutubular junction, whereas the ventricular orifice is located within the interleaflet triangle between the right and left aortic sinuses. CONCLUSIONS: Aorto-left ventricular tunnels bypass the normal ventriculoarterial junction but do not penetrate the septal musculature. This has implications for the fine-tuning of surgical repair.

Location of the coronary arterial orifices in the normal heart.

We examined the coronary arterial orifices in relation to the aortic valve to determine the range of normality in 23 normal hearts from autopsied adults. We determined the position of the zones of apposition between leaflets, the size of the leaflets, the number, position, and shape of the coronary arterial orifices, and their relation to the sinutubular junction. The aortic valve had three leaflets in all specimens, nearly equally spaced around the aorta. The left coronary artery arose within the left posterior aortic sinus (of Valsalva) in 16 (69%) specimens, above the sinutubular junction in five (22%), and at the level of the junction in two (9%). The distance of the left orifice from the zone of apposition between the left posterior and anterior aortic leaflets was between 13% and 61% of the width of the aortic sinus at the sinutubular junction. The right coronary artery arose within the anterior aortic sinus in 18 (78%) specimens, above the junction in three (13%), and at the level of the junction in two (9%). The distance of the orifice from the zone of apposition between the leaflets hinged from the anterior and right posterior aortic sinuses was between 5% and 62% of the width of the aortic sinus at the sinutubular junction. An accessory coronary orifice was found in the anterior aortic sinus in 17 (74%) specimens, whereas a third orifice in this sinus was found in five hearts. The coronary arterial orifices are usually located within the aortic sinuses below the sinutubular junction, but are rarely centrally located. Accessory coronary arterial orifices are found in the majority of the anterior aortic sinuses.

Congenital heart disease and sudden death in the young.

Sudden death is a frequent mode of fatal outcome in cardiac disease and does not exclude young people. The aim of this investigation was to establish whether and to what extent sudden death in the young may be ascribable to the substrate of underlying congenital heart disease. Among 182 young people (< or = 35 years) who died of cardiac sudden death and underwent postmortem examination, 58 (32%) had congenital heart disease. Seven showed an intrapericardial rupture of aortic dissection, in the setting of Marfan syndrome in two, isolated bicuspid aortic valve in two, and bicuspid aortic valve and isthmic coarctation in three; all exhibited equally severe degeneration of the aortic wall. Sixteen cases had conduction system anomalies, mostly bypass tracts; 15 coronary artery anomalies (three ostial valve-like stenosis, five origin from the wrong aortic sinus, and seven deep intramyocardial course); 12 hypertrophic cardiomyopathy; five postoperative congenital heart disease including scar following ventriculotomy, conduction system injury, and defects left unrepaired; and three congenital aortic valve stenosis. One third of sudden deaths in the young was ascribable to structural defects present since birth. A large spectrum of congenital heart disease involves the risk of sudden death, but most structural defects are usually not considered to be life threatening. Some of these concealed defects are potentially detectable in life by clinical imaging techniques.