Risk of arrhythmia in type I myotonic dystrophy: the role of clinical and genetic variables.

OBJECTIVE: To examine the association between the presence of arrhythmia in type 1 myotonic dystrophy (DM1) and clinical-genetic variables, evaluating their role as predictors of the risk of arrhythmia. METHODS: 245 patients with genetically proven DM1 underwent clinical and non-invasive cardiological evaluation. Severity of muscular involvement was assessed according to the 5 point Muscular Disability Rating Score (MDRS). Data were analysed by univariate and multivariate models. RESULTS: 245 patients were examined and cardiac arrhythmias were found in 63 subjects, 40 of whom required a device implant. Statistical analyses revealed that men had more than double the risk of developing arrhythmias compared with women (p = 0.018). Addition of each year of age caused an increased risk of arrhythmia equal to 3% (p = 0.030). Subjects with MDRS 5 had a risk of arrhythmia 12 times higher than patients with MDRS 1-2 (p<0.001). Although all of these variables were significantly associated with cardiac rhythm dysfunction, they had a low sensitivity for the prediction of arrhythmic risk CONCLUSION: Male sex, age and muscular disability were strongly associated with the development of arrhythmia in DM1. However, all of these variables were weak predictors of arrhythmic risk. These results suggest that other factors may be involved in the development of cardiac conduction abnormalities in DM1.

Rate-control or rhythm-control: where do we stand?

Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified.

Results of biventricular endomyocardial biopsy in survivors of cardiac arrest with apparently normal hearts.

Seventeen young patients (10 males and 7 females, aged 14 to 38 years, mean 26.4) without overt organic heart disease, who had been resuscitated from sudden cardiac arrest and referred to our institution during the period 1984 to 1993 for diagnostic evaluation and electrophysiologic study-guided antiarrhythmic therapy, were studied. Patients underwent noninvasive (electrocardiography, echocardiography [2-dimensional and Doppler], and magnetic resonance imaging) and invasive (left ventricular [LV], right ventricular [RV], and coronary angiography, ergonovine testing, electrophysiologic study, and biventricular endomyocardial biopsy) cardiac studies. Six to 8 biopsy fragments per patient were processed for histology and electron microscopy and read by a pathologist blinded to clinical data. Antiarrhythmic drug testing included amiodarone, propafenone, and metoprolol. A cardioverter-defibrillator was implanted in patients with persistently inducible sustained ventricular tachycardia or ventricular fibrillation. Sequential cardiac biopsy specimens were obtained in patients with active myocarditis undergoing immunosuppressive treatment. Periodic 3-month follow-ups included echocardiography and Holter monitoring. Two groups of patients were distinguished by invasive and noninvasive examinations: group I consisted of 9 patients with entirely normal parameters; group II consisted of 8 patients with structural, nonspecific cardiac abnormalities. In this latter group, mild to moderate dilatation and hypokinesia of the left ventricle were documented in 4 patients, concentric LV hypertrophy was seen in three patients, and RV dysfunction was noted in 1 patient. Histologic examination was abnormal in in all patients and revealed specific lesions in 65% of them; LV biopsy specimens allowed a diagnosis in 3 of 7 myocarditic patients with normal RV histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular arrhythmia induced by programmed ventricular stimulation after acute myocardial infarction.

The prevalence, characteristics and clinical significance of ventricular electrical instability with programmed ventricular stimulation was studied in 50 hemodynamically stable patients 17 to 40 days after acute myocardial infarction (AMI) using double extrastimuli at 2- and 10-mA intensity and from 2 right ventricular sites. Ventricular electrical instability was defined as induction of 10 or more consecutive intraventricular reentrant beats. Of 50 patients, 23 (46%) had ventricular electrical instability (10 of these had sustained ventricular tachycardia [VT] induced). No significant differences were observed between patients with and without ventricular electrical instability with respect to age, site of AMI, coronary prognostic index, maximal level of CK, number of narrowed coronary arteries and presence of severe wall motion abnormalities. During a mean follow-up of 11.2 months no patient died suddenly. During repeated Holter recordings patients with ventricular electrical instability had a higher incidence of nonsustained VT than did patients without ventricular electrical instability.

Cardiac biopsy in patients with "primary" atrial fibrillation. Histologic evidence of occult myocardial diseases.

Fourteen patients (ten men and four women; mean age, 37 years) with lone atrial fibrillation (AF) (1 to 18 months' duration) were evaluated by thyroid function tests, two-dimensional echocardiography, hemodynamics, coronary angiography, and left ventricular endomyocardial biopsy, because of unresponsiveness to the usual antiarrhythmic therapy. The results of the T3, T4, TSH, and TRH tests were normal in all patients; cardiac valves and ventricular and atrial sizes (left atrium less than 40 mm) were within the normal limits; also normal were LVEDP (less than or equal to 10 mm Hg) and EF (greater than 0.50). Histologic findings were abnormal in all cases, with three patients showing cardiomyopathic changes, three other patients showing active myocarditis (lymphocytic in two and eosinophilic in one), and eight patients with nonspecific necrosis or fibrosis or both. Steroids (prednisone; 50 mg/m2 of body surface area daily) used in addition to antiarrhythmic therapy in patients with eosinophilic and lymphocytic active myocarditis were able to cause reversion to sinus rhythm, while the other patients continued to have AF. This study documents that occult myocardial diseases (myocarditis, cardiomyopathy, and nonspecific necrosis or fibrosis) can underlie "primary" AF. The addition of steroids to antiarrhythmic therapy in patients with refractory AF and histologic evidence of active myocarditis seems to be useful in controlling the arrhythmia.

Electrophysiologic effects of somatostatin in man.

Experimental and clinical studies suggest that somatostatin, a regulatory peptide widely distributed in human tissues may have electrophysiologic effects. We studied a group of 14 patients who underwent a complete electrophysiologic study for different rhythm disturbances. Somatostatin significantly increased the spontaneous cycle length, the atrial and atrioventricular nodal effective refractory periods, and the Wenckebach cycle length. The AH and HV intervals during sinus rhythm remained unchanged. The effectiveness of somatostatin to interrupt paroxysmal supraventricular tachycardias was assessed in 18 patients. Termination was obtained in 15 (82.5%). Our results show that somatostatin has a significant electrophysiologic effect on the human heart, and confirm its clinical effectiveness in some arrhythmias.

Impact of consistent atrial pacing algorithm on premature atrial complexe number and paroxysmal atrial fibrillation recurrences in brady-tachy syndrome: a randomized prospective cross over study.

AIM OF THE STUDY: The Consistent Atrial Pacing (CAP) algorithm has been designed to achieve a high percentage of atrial pacing to suppress paroxysmal atrial fibrillation. The aim of our study was to compare the impact of DDDR+CAP versus DDDR pacing on paroxysmal atrial fibrillation recurrences and triggers in patients with Brady-Tachy Syndrome. METHODS: 61 patients, 23 M and 38 F, mean age 75+/-9 y, affected by Brady-Tachy Syndrome, implanted with a DDDR pacemaker, were randomized to DDDR or DDDR+CAP pacing with cross over of pacing modality after 1 month. RESULTS: 78 % of patients in DDDR pacing and 73 % in DDDR + CAP pacing (p=n.s.) were free from symptomatic paroxysmal atrial fibrillation recurrences. During DDDR+CAP pacing, the atrial pacing percentage increased from 77+/-29 % to 96+/-7 % (p<0.0001). Automatic mode switch episodes/day were 0.73+/-1.09 in DDDR and 0.79+/-1.14 (p=n.s.) in DDDR+CAP. In patients with less than 50 % of atrial pacing during DDDR, automaticmode switch episodes/day decreased during DDDR+CAP from 1.13+/-1.59 to 0.23+/-0.32 (p<0.05) and in patients with less than 90 % from 1.23+/-1.27 to 0.75+/-1.10 (p<0.001). The number of premature atrial complexes per day decreased during DDDR + CAP from 2665+/-4468 to 556+/-704 (p<0.02). CONCLUSION: CAP algorithm allowed continuous overdrive atrial pacing without major side effects. Triggers of paroxysmal atrial fibrillation induction, such as premature atrial complexes, were critically decreased. Paroxysmal atrial fibrillation episodes were reduced in patients with atrial pacing percentage lower than 90 % during DDDR pacing.

Severe involvement of the conduction system in a patient with sclerodermal heart disease. An electrophysiological study.

A case of progressive systemic sclerosis with syncopal symptoms is reported. The presenting ECG pattern was that of an anterior myocardial infarction. The clinical history and the coronary angiography excluded significant coronary atherosclerotic heart disease. The ECG pattern evolved from the infarctual pattern associated with right bundle branch block to probably major degree of right bundle branch block associated with left posterior fascicular block. M-mode echocardiography, heart catheterization and angiographic studies did not reveal significant mechanical impairment of the left or right ventricle function. His bundle electrogram documented a markedly prolonged H-V interval, confirming an advanced impairment of distal conducting system. This case supports the suggestion that intraventricular conduction disorders in sclerodermal heart disease are not always related to diffuse myocardial involvement. The risk of sudden death justifies accurate electrophysiological evaluation in selected patients with sclerodermal cardiopathy.

[Orthogonal ECG and a statistical system for computer diagnosis with ECG in chronic obstructive pneumopathy]. / L'ECG ortogonale ed un sistema statistico di diagnosi automatizzata dell'ECG nella pneumopatia ostruttiva cronica.

In 92 patients affected from chronic obstructive pulmonary disease (C.O.P.) undergoing spirometric evaluation, the ability of the Pipberger computer program for electrocardiographic interpretation to predict the presence of pulmonary disease with or without right ventricular hipertrophy was compared with that of the manually measured conventional and orthogonal (Frank system) electrocardiogram. The patients were classified as having mild, moderate and severe C.O.P. on the basis of spirometric data. Each system predicted the presence of C.O.P. with low sensitivity. P voltage in D2 greater than or equal to 2 mm (27,1%) and R/S voltage ratio in V5-V6 greater than or equal to 1 (22,8%) were the single conventional criteria more frequently satisfied. Results for 3 lead manual readings were only slightly lower: recognition rate of the R/S voltage ration in x lead less than or equal to 1,3 was 15,7%. The Pipberger program probabilistic answers were divided in "completely" and "partially" correct. Combined completely or partially correct diagnoses were made by the program 14,3% of patients with mild C.O.P., 17,2% of moderate and 48,8% of severe C.O.P. These results suggests that the Pipberger program has at least similar ability to predict C.O.P. compared with the 12 lead and orthogonal manually measured electrocardiogram.

[Surface recording technique of His bundle potential in man]. / Tecniche di rilevamento e di calcolo e risultati della registrazione esterna del potenziale del fascio di His.

A method is presented for the non-invasive recording of His bundle electrical activity from the body surface in man. Several bipolar ECG leads were employed: precordial, Frank "x" and Frank "z". Signals were filtered (30-300 Hz), highly amplified (5 x 104) and averaged. Digital averaging was performed on line by a microcomputer (OTE Biomedica Neuroaverager mod. 1172). Surface investigation was performed in 10 patients affected by different conduction pathology simultaneously with HBE recordings for diagnostic purpose and in 5 normal volunteers only incruently. Highly repeatable electrical deflections (B waves) were recorded in the PR segment. In all patients a good correspondence between surface (B wave) and intracardiac (H wave) was found. Atrial pacing and pharmacological test were used in order to ascertain the real source of B wave.

[Automatic analysis of systolic time intervals using polygraphic examinations]. / L'analisi automatica dell'esame poligrafico.

For clinical purpose, poligraphyc signals are analyzed: systolic time intervals (STI) and all other significative magnitudes are measured. A system of modular programs (ATS), in Assembler and Fortran IV languages, digitalizes, filters and analyzes three simultaneous analogical signals: ECG, PCK and CP. ATS, adapted polynomial and gonyometrics leats-squares smoothings to the signals for leaving-out spikes and drifts, employs algorhythms that, by a statistic knowledge of the thresholds of the fist derivative of each signal and of the globality of smoothed signals, converge to the measures of the required significative magnitudes. A statistic investigation (on 100 samples) showed that ATS is better than every manual analysis in terms of efficiency, speed and amount of information. In conclusion ATS program is suitable for clinical purposes.

Spinal cord stimulation in patients with refractory anginal pain and normal coronary arteries.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in patients with refractory angina and coronary artery disease. No previous study assessed the clinical effects of SCS in patients with refractory angina who present angiographically normal coronary arteries. METHODS: SCS was performed in 7 patients (4 men, 3 women, mean age 59.3 +/- 11 years) with refractory angina and normal coronary arteries. Clinical status was assessed 1 month after SCS device implantation and at a mean follow-up of 11 months (range 2-17 months) by: 1) an estimate of the number of anginal attacks and nitrate consumption in the 2 weeks prior to implantation and to follow-up visits; 2) a score of quality of life by a visual analogic scale; 3) a five-item questionnaire assessing effort angina and satisfaction with treatment; 4) treadmill exercise testing. RESULTS: At the last follow-up the number of anginal episodes (p < 0.001) and nitrate consumption (p < 0.004) were both reduced by SCS. Visual analogic scale score improved from 2.1 +/- 0.98 to 9.0 +/- 0.9 (p < 0.001) at 1 month and to 6.4 +/- 2.3 (p < 0.01) at the last follow-up. Questionnaire analysis showed that mild (p = 0.006) and moderate (p = 0.000) physical activity, as well as patient satisfaction with anginal status (p = 0.000) and with current treatment (p = 0.000) all improved by SCS. Finally, time to 1 mm ST segment depression, time to angina, and exercise duration were all prolonged by SCS. CONCLUSIONS: Our data point out that SCS may considerably improve anginal symptoms and exercise tolerance in a significant number of patients with refractory angina and normal coronary arteries and therefore it should be considered as a valuable treatment option in this group of patients.

Sleep-related breathing disorder and bradyarrhythmias, why to use continuous positive airway pressure (CPAP) treatment: a case report.

In this report we describe the case of a 69-year-old woman, with a medical history of onset of asthenia, worsening of dyspnoea for mild efforts (class NYHA II) and events of nocturnal dyspnoea (without orthopnea or edema of lower limbs). The patient presents hypertension, dyslipedaemia and obesity (BMI 38 kg/m²) as cardiovascular risk factor. A previous 24-h Holter monitoring documents bradycardic events and sinusal pauses. The ergometric test and the echocardiogram do not show particulary pathological features. After a careful anamnesis about nocturnal events of dyspnoea and about daytime tiredness, and the Epworth questionnaire regarding the relationship between sleep-related breathing disorder and cardiovascular disease, we perform cardiorespiratory sleep study that shows a diagnosis of obstructive sleep apnea syndrome (OSAS). The patient begins therapy with continuous positive airway pressure (CPAP) during the night. It is shown a considerably decrease of bradycardic events during the night after a period of this treatment.

Ximelagatran/melagatran against conventional anticoagulation: a meta-analysis based on 22,639 patients.

BACKGROUND: The oral direct thrombin inhibitor ximelagatran, and its active form, melagatran, have been tested in various clinical conditions as a promising alternative to conventional anticoagulant therapy (CAT), despite some concerns over potentially serious liver injury. OBJECTIVES: To assess its risk/benefit profile, a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing xi-/melagatran to CAT was performed. METHODS: Leading medical databases were searched. The rates of major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, nonfatal pulmonary embolism), major bleeds (MB), and hepatotoxicity were compared. Out of 140 potentially relevant citations, 13 RCTs enrolling 22,639 patients were included. Indications for treatment were: 1) perioperative prophylaxis of deep vein thrombosis (DVT); 2) management of DVT; and 3) stroke prevention in atrial fibrillation. RESULTS: Overall, the risk of MAE (OR 0.98 [0.83-1.17]) and MB (OR 1.01 [0.69-1.47]) did not differ significantly between xi-/melagatran and CAT. There was a clear trend towards an increased risk of hepatotoxicity (OR 1.74 [0.50-6.01]), with an incidence of 5.8% with xi-/melagatran versus 2.3% with CAT (p<0.001); more specifically, the rate of hepatotoxicity was markedly augmented in the management of DVT (OR 5.16 [3.38-7.89]), for treatment durations > or = 3 months (OR 6.73 [5.01-9.05]), and in the prevention of atrial fibrillation-related stroke (OR 8.31 [5.65-12.23]). Two fatal cases of liver injury occurred with xi-/melagatran. CONCLUSIONS: Although comparable to CAT in terms of MAE and MB, xi-/melagatran carries a prohibitive risk of hepatotoxicity that cannot be ignored. Newer long-term alternatives are urgently needed.

Multiform ventricular ectopic rhythm by combined parasystolic and reentrant activities.

Multiform ventricular ectopic rhythm (MVER), i.e., at least two QRS configurations of ventricular ectopic beats (VEBs), was assessed by 24-hour ambulatory ECG recording in four patients with ventricular parasystole (VP). In two of these four patients, VEBs with fixed coupling to the preceding impulses coexisted with VP beats of different configuration. In case no. 1, the VEBs had an identical coupling interval to sinus beats and VP beats, suggesting a mechanism of reentry elicited from both dominant pacemakers. In case no. 2, an intermittent form of VP due to type II second-degree entrance block was present. In this patient, the VEBs were coupled to sinus beats and to sinus-VP fusion beats and appeared to be dependent on the sinus beats reaching the VP focus. A mechanism of reentry determined by the penetration of sinus beats into the VP area, with prematurity-dependent aberrancy of VEBs, was suggested for the coupled VEBs in this patient. These observations suggest that the coexistence of an automatic ventricular ectopic focus and of a reentrant activity determined by, or elicited from, an area of automaticity may constitute the underlying mechanism of MVER in some patients.

Catheter induced distal intra-Hisian right bundle branch block in a patient with persistent proximal intra-Hisian complete A-V block.

We describe a patient with complete intra-Hisian A-V block and narrow QRS who developed catheter-induced right bundle branch block during an electrophysiological study. Selective His bundle pacing was performed during complete intra-Hisian A-V block and right bundle branch block pattern; the distal His bundle pacing normalized the QRS complex, while a more proximal His bundle stimulation showed a right bundle branch block configuration with the persistence of the proximal intra-Hisian lesion responsible for the complete A-V block. These electrophysiological findings suggest that the catheter-induced right bundle branch block in our patient was due to a focal lesion in the distal part of the main His bundle. To our knowledge, this is the first report of documented multilevel lesions within the His bundle in man.