Miraglia G

Juvenile sudden death and effort ventricular tachycardias in a family with right ventricular cardiomyopathy

A family with occurrence of juvenile sudden death and effort polymorphous ventricular tachycardias is reported. Nineteen members aged 9 to 63 years were investigated. Four of them died suddenly in their youth. Postmortem investigation performed in 2 deceased subjects disclosed an apparently normal heart at macroscopy but fibro-fatty substitution of the right ventricular free wall was noted at histologic examination. The 14 living members underwent physical examination, resting electrocardiography, chest X-radiography, Holter monitoring, exercise stress testing, and M-mode and cross-sectional echocardiography. Four patients underwent hemodynamic and electrophysiologic studies. All 14 subjects had normal physical examination as well as normal electrocardiographic and cardiothoracic indices. Localized right ventricular structural and dynamic abnormalities were noted at cross-sectional echocardiographic and angiographic investigation of 9 of the patients. The right ventricular volumes in these subjects were normal or slightly increased. In 7 of them, polymorphous ventricular tachycardias were induced by exercise stress testing. The arrhythmias which were responsive to beta-blockade, do not seem to depend on reentry. Enhanced automaticity appeared to be the more likely mechanism of their production. These data demonstrate that right ventricular cardiomyopathy may occur in an occult form with life-threatening electrical instability.

Accelerated idioventricular rhythm of infundibular origin in patients with a concealed form of arrhythmogenic right ventricular dysplasia.

Five apparently healthy people (aged 16-47) presented with recurrent episodes of accelerated idioventricular rhythm characterised by left bundle branch block and right axis deviation. Clinical history, physical findings, basic electrocardiogram, chest x ray, and blood tests were within normal limits in all. Holter monitoring, exercise stress test, and electrophysiological study (in three patients) showed that accelerated idioventricular rhythm was mainly bradycardia dependent, easily suppressed by effort and overdrive pacing, and originated from the outflow tract of the right ventricle. The mechanism could be enhanced automaticity. Data from cross sectional echocardiography (in all patients) and from haemodynamic evaluation (in three) identified structural or wall motion abnormalities of the right ventricle or both without appreciable dilatation of the ventricle. Biopsy specimens of the right ventricular endomyocardium showed fibrosis in one patient, fibrosis and fatty infiltration in the second, and pronounced fatty infiltration in the third. These results show that some patients with accelerated idioventricular rhythm have right ventricular abnormalities that are typical of the localised and concealed forms of arrhythmogenic right ventricular dysplasia.

Low- and medium-dose diltiazem in chronic atrial fibrillation: Comparison with digoxin and correlation with drug plasma levels

The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation. The relationship between drug plasma levels and cardiovascular effects was also investigated. After 7 days of combined therapy with diltiazem (60 mg three times a day in 10 patients and four times a day in nine patients) and digoxin (0.125 mg/day in two patients and 0.250 mg/day in 17 patients), the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3% in comparison with digoxin therapy alone; the serum digoxin level was not significantly changed (1.06 +/- 0.43 vs 1.05 +/- 0.61 ng/ml). After a standardized bicycle exercise test (50 watts for 3 minutes), maximal heart rate was reduced by 19.9%, diastolic blood pressure was decreased by 8.9%, and systolic pressure-rate product was decreased by 12.5%. Diltiazem plasma levels (mean 120.9 +/- 63.3 ng/ml) were linearly correlated with percentage variations in maximal heart rate, diastolic blood pressure, systolic blood pressure, and pressure-rate product during exercise. Eighteen patients in succession discontinued digoxin therapy; after 14 days of diltiazem alone, the 24-hour mean heart rate returned to control values of digoxin therapy, whereas maximal heart rate and pressure-rate product during exercise were significantly reduced (-17.2% and -14.1%, respectively), with no changes in blood pressure. Diltiazem plasma levels (135.0 +/- 83.2 ng/ml) showed a linear correlation with the percentage of reduction in maximal heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity, specificity and predictive accuracy of Q wave, QXQT ratio, QTc interval and ST depression during exercise testing in men with coronary artery disease

One hundred forty-three subjects (107 with coronary artery disease [CAD], 23 without CAD [evaluated by coronary angiography] and 13 athletes) were selected for this study. All subjects underwent exercise testing to evaluate sensitivity, specificity and predictive value of Q wave, QX/QT ratio, QTc interval and ST depression. The Q-wave analysis revealed less sensitivity (49%) and less specificity (83%) than ST depression (71% and 97%, respectively). The QTc criterion had greater sensitivity (80%) than ST depression but less specificity (11%). The QX/QT criterion was no different in sensitivity (74%) but had less specificity (69%). To establish the statistical evaluation of the positive predictive value in CAD, variations in the prevalence of the disease were considered. A 90% prevalence gives the best positive predictive value on all evaluated measurements, between 100% for ST depression and 89% for the QTc criterion. A 5% prevalence, however, gives an acceptable positive predictive value only on ST-segment depression (57%).

Type A behavior pattern and mortality after recurrent myocardial infarction: preliminary results from a follow-up study of 5 years

The purpose of the current study is to examine the association between the type A Behavior Pattern (TABP) and recurrent myocardial infarction (RMI). Rosenmans Structured Interview was administered to a consecutive series of patients admitted to the hospital for myocardial infarction (n = 88). Incidence and mortality from RMI in relation to TABP categories were evaluated after a follow-up period of 5 years. The number of new episodes of myocardial infarction observed in the extreme categories was nearly the same but the number of subjects who dies was nearly twice as large in the B as in the A1 category (10.3% vs. 5.8%, chi 2 = 9.074, p less than 0.0283). No subject was observed to survive after RMI in the B group. In agreement with other recent studies, our preliminary results failed to confirm the association between TABP and RMI, but showed a protection from death for subjects displaying high TABP levels. This finding is discussed in terms of the possibility for type A subjects to cope better with the acute illness.

Arrhythmogenic right ventricular dysplasia. Study of a selected population

Le informazioni ottenibili con l’indagine FFR, in molti contesti clinici ed angiografici, sono cruciali nella pianificazione di una procedura di rivascolarizzazione percutanea coronarica. Questo strumento permette di identificare immediatamente la criticità funzionale di una lesione evitando di dover ricorrere all’esecuzione di test non invasivi (scintigrafia miocardica, ecocardiografia da stress, test ergometrico) per la ricerca di ischemia miocardica inducibile/ridotta riserva coronarica. Il trattamento dei sintomi (angina) e la riduzione della quota di ischemia miocardica inducibile sono gli obiettivi principali della procedura coronarica percutanea (PCI) nei pazienti affetti da coronaropatia stabile. Pertanto, la FFR trova il suo principale impiego nell’ambito della coronaropatia stabile. Sarà scopo di questo documento fornire una guida pratica al cardiologo interventista per l’utilizzo di questa metodica senza tralasciare il punto di vista del cardiologo clinico che si trova quasi sempre per primo a valutare il paziente con coronaropatia stabile.Fractional flow reserve (FFR) is considered the gold standard for functional assessment of coronary stenosis in stable coronary artery disease. The use of FFR enables an ischemia-guided revascularization with improvement of clinical outcomes in a cost-effective fashion. Both clinical and interventional cardiologists should be aware of the advantages and potential pitfalls of this technique. We focus on FFR with the aim to provide the clinical cardiologist with information on indications and technical aspects to confirm a correct execution of FFR in different coronary anatomical settings.

Early reduction in plasma norepinephrine during beta-blocking therapy with metoprolol in chronic heart failure

BACKGROUND The possible role exerted by modulation of sympathetic outflow in the clinical effects of beta-blockade in chronic heart failure was tested during short- and long-term treatment. METHODS AND RESULTS Oral metoprolol (30-150 mg/day) was added to conventional therapy in 14 patients with idiopathic dilated cardiomyopathy, left ventricular ejection fraction (LVEF) of <0.45, and New York Heart Association class II or III. Norepinephrine plasma levels, which are an index of sympathetic activation, decreased by 27.57 +/- 18.03% after 1 month (P < .005), but returned to pretreatment levels after 6 months. LVEF increased by 7.7 +/- 6.0 ejection fraction units after 6 months (P < .005 vs baseline and P < .05 vs 1 month). Long-term beta-blockade resulted in nonsignificant improvements in functional class, symptom score, and oxygen consumption at peak exercise. After 1 month, the reduction in plasma norepinephrine levels and the changes in LVEF were inversely correlated (P < .01). No other correlation emerged during short- or long-term treatment. CONCLUSION In conclusion, the reduction in plasma norepinephrine levels during short-term beta-blockade was not proportional to the clinical benefits and may have been attributed to the direct inhibition of sympathetic outflow. The early reduction in circulating norepinephrine levels may decrease cardiac performance through withdrawal of sympathetic support when the favorable effects of beta-blockade have not had time to occur. The role that sympathetic modulation may exert in the long-term clinical benefits of metoprolol deserves further investigation.

Monomorphic repetitive rhythms originating from the outflow tract in patients with minor forms of right ventricular cardiomyopathy.

We studied in detail 17 patients presenting with monomorphic repetitive ventricular rhythms having left bundle branch block morphology and right axis deviation. All had an apparently normal heart at physical examination. At chest radiography, three patients had mild cardiomegaly, and at electrocardiography, five patients had inverted T waves beyond V2. Five patients had syncope or near syncope. In seven patients the tachycardia occurred on effort. One patient died suddenly. The patients were extensively investigated, using cross-sectional echocardiography, complete haemodynamic and angiographic studies, electrophysiology and histology, to search for any structural basis of the arrhythmias. Tachycardia was sustained in 8 patients, nonsustained in 3, and consistent with accelerated idioventricular rhythm and repetitive paroxysmal ventricular tachycardia in 5 and 1 patients, respectively. Despite the differences in clinical and arrhythmologic features, similar abnormalities of right ventricular structure and/or wall motion were detected in all patients, consistent with localized forms of right ventricular cardiomyopathy. Different antiarrhythmic drugs were successfully used in twelve patients (the four patients with accelerated idioventricular rhythm were not treated). The patient who died suddenly had previously had a sustained ventricular tachycardia and was being treated by beta-blockade. Postmortem study revealed massive fibro-adipose substitution of the right ventricular free wall and pulmonary infundibulum.

Changes in structure and function of the human left ventricle after acclimatization to high altitude

SummaryTo analyse the role of changes in structure and function of the left ventricle in determining cardiac function at rest and during exercise, several two-dimensional and Doppler echocardiographic measurements were performed on 11 healthy subjects immediately before an Himalayan expedition (Nun, 7135 m), during acclimatization (3 weeks) and 14 days after the return. At rest decreases were found in cardiac index (CI) (3.23 l · min−1 · m−2, SD 0.4 vs 3.82 l · min−1 · m−2, SD 0.58,P < 0.01), left ventricular mass (55.3 g · m−2, SD 9.4 vs 65.2 g · m−2, SD 13.5,P < 0.005) and left ventricular end-diastolic volume (LVEDV) (53.9 ml · m−2, SD 6.9 vs 64.8 ml · m−2, SD 9.1,P < 0.001) after acclimatization; by contrast the coefficient of peak arterial pressure to left ventricular end-systolic volume (PAP/ESV) (7.8, SD 1.6 vs 6.0, SD 1.8,P < 0.005) and mean wall stress [286 kdyn · cm−2, SD 31 vs 250 kdy · cm−2, SD 21 (2.86 N · cm−2, SD 0.31 vs 2.50 N · cm−2, SD 0.21),P < 0.005] increased. After return to sea level, low values of CI and mass persisted despite a return to normal of LVEDV and preload. A reduction of PAP/ESV was also observed. At peak exercise, PAP/ESV (8.7, SD 2.4 vs 12.8, SD 2.0,P < 0.0025), CI (9.8 l · min−1 m−2, SD 2.5 vs 11.61 · min−1 · m−2, SD 1.6,P < 0.05) and the ejection fraction (69%, SD 6 vs 76%, SD 4,P < 0.05) were lower after return to sea level than before departure. The depressed left ventricular performance after prolonged exposure to hypoxia may be related to changes in structure and function including reduction in preload, loss of myocardial mass and depression of inotropic state.

Medium-Term Assessment of Isosorbide-5-Mononitrate in Effort Angina: Dependence of Efficacy on Basic Hemodynamic Conditions

Chronic nitrate therapy in stable angina has revived after the introduction of the long- acting organic nitrates [1–3], and particularly after the introduction of isosorbide-5-mononitrate (IS-5-MN) which, among the long-acting nitrates, has the most favorable kinetics [4–8]. The mechanism of action of nitrates is far from being fully clarified; however, increasing evidence points towards an activation of a cyclic GMP-dependent relaxation of smooth muscle [2, 3] of the large vessel walls, which implies an increase in arterial [9] and venous capacitance [10], i.e., an increase in vascular compliance [11]. At therapeutic doses peripheral resistance does not seem to be affected [12–14].