Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis.

BACKGROUND: Adjuvant Trastuzumab with chemotherapy is the gold standard for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (HER2+ EBC). Older patients have been largely under-represented in clinical trials, and few data on Trastuzumab cardiotoxicity have been reported in this subgroup. PATIENTS AND METHODS: Four hundred and ninety-nine consecutive HER2+ EBC patients were treated with adjuvant trastuzumab and chemotherapy (aTrastC) at 10 Italian institutions. We evaluated disease prevalence and patient characteristics in the patients older than 60 years of age (over-60), prevalence of aTrastC cardiotoxicity and risk factors. RESULTS: There were 160 'over-60' patients (32%), in whom a higher prevalence of hypertension, diabetes, renal dysfunction, dyslipidemia and treatment with ACEi (40 versus 8%) and beta blockers (20 versus 8%) was found than in the younger patients (339 = 68%). Clinical heart failure occurred in 6% of the 'over-60' and in 2% of the younger patients. A reduction in left ventricular ejection fraction of >10 points was detected in 33% of the 'over-60' and in 23% of the younger patients (all P < 0.05). aTrastC was discontinued in 10% of the 'over-60' and in 4% of the younger patients (P = 0.003), restarted in 44% of the 'over-60' and in 58% of the younger women (P = ns). CONCLUSION: In clinical practice, 32% of HER2+ EBC patients treated with aTrastC are 'over-60'. These patients have an increased cardiovascular risk profile and develop aTrastC cardiotoxicity commonly.

Role of telecardiology in the assessment of angina in patients with recent acute coronary syndrome.

We compared two models of assistance (telecardiology versus usual care) for patients discharged after acute coronary syndrome (ACS), in the assessment of angina. Two hundred patients were randomized into two groups at discharge for ACS: Group A to telecardiology and Group B to usual care. Early hospital readmission (in the first month) occurred in 16 patients (seven in Group A and nine in Group B). Six of Group A were readmitted for a cardiac cause (non-cardiac in one). Angina was the only cardiac cause. Five of the Group B patients were readmitted for a cardiac cause (non-cardiac in four). The results of the present study emphasize that patients with ACS suffer from a definite rate of cardiac symptoms within the first month (63%). Angina occurs more frequently within the first two weeks (68% of cases). Telecardiology slightly reduces hospital readmissions (telecardiology 44% versus usual care 56%), but better identifies true angina.

[Management programs for elderly patients with chronic heart failure]. / Programmi di gestione dell'anziano con scompenso cardiaco cronico.

PURPOSE: Most patients with heart failure are elderly with multiple coexisting diseases and heart failure is the most common discharge diagnosis in elderly hospitalized patients. Despite major advances in the pharmacotherapy of heart failure, hospitalization rates remain high, owing in large part to a multitude of psychosocial, behavioral, and financial factors that serve as barriers to effective compliance with prescribed treatment. In the last decade, several models have been proposed in order to optimise the long-term management of elderly patients with heart failure. DESIGN: A review of most significant and recent models available was performed. RESULTS: Several studies have documented the efficacy of specialized multidisciplinary heart failure disease management programs in terms of reducing hospital utilization, improving quality of life, functional capacity, patient satisfaction, compliance with diet and medications and decreasing cost of care. CONCLUSIONS: At present, the greatest challenge in managing elderly heart failure patients is to more effectively implement proven treatments and disease management systems.

[Beta blockers in elderly with heart failure]. / I betabloccanti nel paziente anziano con scompenso cardiaco.

Despite the importance of beta-blockers for secondary prevention after acute myocardial infarction, several studies suggested that they are substantially underutilized, particularly in elderly patients. Actually no randomized clinical trial including elderly patients with heart failure treated with beta-blockers is reported in the literature. However, previous studies showed that beta-blocker therapy was associated with a reduction in total cardiac mortality (-40%) of elderly patients with acute myocardial infarction without left ventricular dysfunction. Furthermore, a meta-analysis of five trials including 1729 patients aged > 60 years with heart failure evidenced a non-significant trend versus total mortality reduction in patients receiving beta-blockers (odds ratio 0.68, 95% confidence interval 0.51-0.93, p = 0.4).

Perioperative prognostic value of dipyridamole echocardiography in vascular surgery: A large-scale multicenter study in 509 patients. EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Patients undergoing major vascular surgery are at a relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for perioperative risk stratification. The aim of the current study was to evaluate the value of dipyridamole echocardiography test (up to 0.84 mg/kg over 10 minutes) in predicting cardiac events in a large-scale, multicenter, prospective, observational study design. METHODS AND RESULTS: Five hundred nine patients (mean age 66+/-10 years) were studied before vascular surgery by dipyridamole stress echocardiography in 11 different centers. All patients underwent preoperative clinical risk assessment according to the American Heart Association guidelines. No major complications occurred during dipyridamole stress echocardiography. Technically adequate images were obtained in all patients; however, in 4 patients only the low dipyridamole dose (0.56 mg/kg over 4 minutes) was given for limiting side effects. Eighty-eight (17.3%) had a positive test. Perioperative events occurred in 31 (6.1%) patients: 6 deaths, 11 myocardial infarctions, and 14 episodes of unstable angina. Sensitivity and specificity of dipyridamole stress echocardiography for predicting spontaneous cardiac events were 81% and 87%, respectively, with a positive predictive value of 28% and negative predictive value of 99%. By multivariate analysis, the difference between wall motion score index at rest and peak stress (Deltawall motion score index), test positivity, and ST-segment depression during dipyridamole infusion were independent predictors of any perioperative cardiac event. CONCLUSIONS: Dipyridamole stress echocardiography is safe and well tolerated in patients undergoing major vascular surgery and provides an effective preoperative screening test for the risk stratification of these patients, mainly because of the extremely high negative predictive value, which is a potent predictor of complication-free procedure.

Myocardial damage after spider bite (Latrodectus tredecimguttatus) in a 16-year-old patient.

The case of a 16-year-old patient with L. tredecimguttatus poisoning complicated by myocardial damage is reported. Symptoms (typical chest pain), electrocardiographic (ST-T changes in precordial leads) and echocardiographic (akinesia of interventricular septum with depressed left ventricular function) features and laboratory findings (increased myocardial enzymes) are described.

[Management of ventricular arrhythmia in chronic congestive heart failure]. / La terapia delle aritmie ventricolari nello scompenso cardiaco cronico.

PURPOSE: To evaluate efficacy and indications of therapy for ventricular arrhythmias in patients with chronic congestive heart failure. DESIGN: A review of most significant and recent clinical trials was performed. RESULTS: In patients with severe left ventricular dysfunction, the desirable actions of antiarrhythmic drugs are attenuated and their negative inotropic and proarrhythmic actions are enhanced. Treatment should be limited to patients with malignant ventricular arrhythmias, or to patients considered at high risk. When indicated, amiodarone is usually well tolerated and safe. The prevention of sudden death in patients with heart failure should be based on optimized therapy of pump failure, reducing left ventricle work load and modulating neurohormonal systems with ACE-inhibitors and betablockers drugs. Further, an important role is held by anti-ischemic therapy, revascularization procedures, anticoagulant therapy and prevention of electrolytes unbalances. Patients with sustained of high risk arrhythmias, resuscitated from a cardiac arrest, should be considered for transvenous Implantable Cardioverter Defibrillator (ICD) implant. CONCLUSIONS: Ventricular arrhythmias are common in heart failure patients, represent an important cause of sudden death and the choice of treatment is difficult because of the complexity of underlying mechanisms, frequency of adverse reactions and the severity of left ventricular dysfunction.

Left atrial leiomyosarcoma: double occurrence and double recurrence--report of one case.

In October 1996 a 67-year-old man underwent transthoracic and transesophageal echocardiography (TEE) because of dyspnea on exertion and was found to have 2 left atrial cardiac masses. The 2 masses were surgically removed from the atrium and showed histopathologic and ultrastructural features of a leiomyosarcoma. Seven months later a double recurrence of left atrial masses was found with TEE; the patient refused surgery and decided instead to receive chemotherapy. In May 1998 he was in stable condition (New York Heart Association class III), but a further growth of the 2 left atrial masses was observed at TEE. We describe the echocardiographic features of the 2 cardiac masses and the clinical and prognostic implications.

Diagnostic and prognostic value of dipyridamole and dobutamine stress echocardiography in patients with Q-wave acute myocardial infarction.

The aim of this study was to compare dipyridamole and dobutamine stress echocardiography, performed early in patients with acute myocardial infarction (AMI) to evaluate residual ischemia, viability, and prognosis. Fifty patients (mean age 55 +/- 9 years, 47 men, 3 women) with AMI, all treated with thrombolytic therapy, underwent standard dipyridamole and dobutamine tests, within the fifth day of the event. Wall motion score index and the 16 segments model were used to evaluate contractility. Forty-seven patients underwent coronary angiography within the tenth day of the event. The mean follow-up was 24 +/- 12 months. No side effects occurred during both tests. Both dipyridamole and dobutamine tests were positive for ischemia, in 32 and 33 of 47 patients, respectively (sensitivity 73% and 75%; specificity 67% and 67%); these tests induced an improvement of contractility in 23 and 38 of 139 abnormal segments at baseline, respectively (sensitivity 52% and 86%; specificity 100% and 100%). Cardiac events occurred in 26 of 50 patients, 22 with a positive dipyridamole test and 21 with positive dobutamine test. Thus, both tests were feasible, safe, and useful to evaluate residual ischemia, viability, and prognosis. No significant differences were found in sensitivity and specificity between tests.

Deceptive surgical results in three siblings with familial Wolff-Parkinson-White syndrome.

Three siblings with familial Wolff-Parkinson-White syndrome and two instances of sudden death are described. In all of them, multiple accessory pathways with a very short anterograde refractory period and rapid ventricular responses during atrial fibrillation had been documented, thus surgical ablation of the bypass tracts had been performed. Although abolition of the accessory pathway conduction had been demonstrated post-operatively, an electrophysiologic evaluation performed after 2-8 years showed resumption of conduction over the anomalous connections, with life-threatening arrhythmias during induced fast atrial rhythms. This report demonstrates that apparent success of surgery for pre-excitation syndrome, judged during the postoperative course, may be illusory in some patients, and return of accessory pathway conduction can occur later on.

Transesophageal electropharmacologic test in a newborn with familial Wolff-Parkinson-White syndrome.

A newborn infant with familial Wolff-Parkinson-White (WPW) syndrome presented with a supraventricular tachycardia of 300 beats/min, refractory to digoxin and flecainide administration. Serial electropharmacologic tests were performed via the esophagus before and during oral therapy with verapamil at 40, 80, and 60 mg daily. Before treatment, tachycardia could be induced with programmed stimulation. A regimen of verapamil at 60 mg daily, which resulted in the initiation of nonsustained (less than 10 s) reciprocating tachycardia only, without clinical recurrences, was identified as suitable long-term oral therapy. The efficacy of this drug regimen in preventing episodes of tachycardia was confirmed during a 1-month follow-up period. It is concluded that transesophageal atrial pacing is a useful, noninvasive means of selecting treatment in neonates with supraventricular tachycardia, when nonconventional drugs are considered for prophylaxis.

[The diagnostic and therapeutic usefulness of adenosine triphosphate in supraventricular tachycardias]. / Utilità diagnostica e terapeutica dell'adenosina trifosfato nelle tachicardie sopraventricolari.

The efficacy and safety of intravenous adenosine-5'-triphosphate (ATP) in supraventricular tachycardia (SVT) were investigated in 40 patients, aged 1 month-69 years (mean 28 years). Thirty-one had a history of paroxysmal supraventricular tachycardia (group A), 9 had chronic supraventricular tachycardia (group B). Four patients in Group A had long R-P' tachycardia. In group A, transesophageal atrial pacing was utilized for tachycardia induction. A ventriculoatrial interval (VA) during tachycardia greater than 70 ms was considered diagnostic for reentry by an AV accessory pathway (AP), while a VA less than or equal to 70 ms suggested reentry within the AV node. Serial rapid intravenous injections of graded doses of ATP were performed in both groups. In 14 patients of group A, graded doses of ATP (0.075, 0.1, 0.125, 0.15, 0.2, mg/kg) were performed in order to analyze the dose-response relationships. In group A, ATP resulted in termination of tachycardia in all patients (21 with reentry by an AP, 10 with intranodal reentry). A total of 77 tachycardia episodes were interrupted. A 100% efficacy was found with doses of greater than or equal to 0.15 mg/kg of ATP. Among patients with AP reentry, interruption in the anterograde limb of the reentry circuit occurred in 16 patients, while termination of tachycardia after retrograde block was observed in 5 patients, 4 of whom with long RP' tachycardia. In group B, ATP resulted in transient 2:1 or high degree AV block in 8 patients. Transient restoration of sinus rhythm was observed in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Two to one atrioventricular block in intranodal re-entry reciprocating tachycardia. Description of 2 cases]. / Blocco atrioventricolare 2:1 durante tachicardia reciprocante da rientro intranodale. Descrizione di 2 casi.

Atrioventricular nodal reentry tachycardia (AVNRT) is a common form of paroxysmal supraventricular tachyarrhythmia. In this tachycardia, the atrium and ventricle are not necessary links of the reentry circuit, so that the arrhythmia may persist in spite of the occurrence of 2:1 AV ratio or AV dissociation. Only a few examples of 2:1 AV block during AVNRT have been described. We report on 2 patients with a history of paroxysmal supraventricular tachycardia in whom 2:1 AV block with persistence of the arrhythmia was documented. Transesophageal electrophysiologic study was performed after pharmacologic wash-out in both patients. During definition of refractory periods, reciprocating tachycardia was initiated when a critical lengthening of the Stimulus-R interval was reached. Tachycardia showed narrow QRS complexes at a rate of 200 (patient 1) and 180 (patient 2) bpm, with the ventriculo-atrial interval (VA) of 45 and 70 ms, respectively. During tachycardia, sustained episodes of 2:1 AV block, without termination of the arrhythmia, occurred in both patients. The tachycardia could be reproducibly terminated by means of extrastimulus technique, rapid burst pacing as well as intravenous injection of adenosine-5'-triphosphate (ATP) at doses of 0.15-0.20 mg/kg. Initiation of tachycardia after a critical lengthening of the Stimulus-R interval and the effectiveness of either rapid burst pacing or ATP injection in the interruption of the arrhythmia, suggested a reentry circuit involving the AV node. The unusual finding of 2:1 AV block during reciprocating tachycardia with a retrograde time conduction (VA interval) equal to or shorter than 70 ms suggested the presence of an intranodal reentry as the substrate of the tachycardia, and excluded the presence of an accessory AV pathway.

Electrophysiological significance of QRS alternans in narrow QRS tachycardia.

To investigate the electrophysiological significance of QRS alternans during narrow QRS tachycardia, transesophageal atrial pacing and recording was performed in 24 patients with a history of paroxysmal supraventricular tachycardia. Standard electrocardiograms showed ventricular preexcitation in 15 patients and normal QRS pattern in nine patients. The ventriculoatrial interval during tachycardia, as defined by means of transesophageal electrogram, allowed tentative diagnosis of the tachycardia mechanism. A 12-lead ECG was recorded either during spontaneous or induced tachycardia, as well as during transesophageal atrial pacing at increasing rates. Electrical alternans occurred spontaneously in eight patients (33%, group A): five with accessory pathway reentry (mean VA: 136 +/- 43 msec), and three with AV nodal reentry (mean VA: 48.3 +/- 12 msec). Tachycardia rate ranged between 170 and 230 beats/min (mean 200.7 +/- 16). In two patients, alternation of the QRS occurred only in the presence of a heart rate exceeding 180 and 190 beats/min, respectively. The amplitude of QRS remained stable during tachycardia in 16 patients (67%, group B): 14 had accessory pathway reentry (mean VA: 137.5 +/- 32 msec), and two had AV nodal reentry (mean VA: 45 +/- 7 msec). In this group, the tachycardia rate ranged from 150 to 210 beats/min (mean 175 +/- 12). Incremental transesophageal atrial pacing up to rates equal to that of tachycardia was performed in five patients from group A and in five patients from group B. Electrical alternans could not be induced in both groups with pacing at progressively increasing rates.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fulguration of the bundle of His. Description of 3 new cases]. / La folgorazione del fascio di His. Descrizione di 3 nuovi casi.

With the purpose to call attention to the clinical utility of fulguration of the His bundle (a therapeutic procedure somewhat neglected in Italy) 3 new cases are presented. All patients had a long history of supraventricular tachyarrhythmias refractory to conventional treatment. Patients 1 and 2, in whom surgical correction of tetralogy of Fallot and mitral valve replacement, respectively, had been performed several years before, had chronic atrial tachycardia with congestive heart failure. Patient 3 suffered from persistent atrial flutter, in the absence of demonstrable organic heart disease. Three shocks of 320 J were necessary to induce complete AV block in patient 1 and 2. In patient 3, a single discharge (320 J) resulted in interruption of AV conduction. Twenty-four hours after the procedure, a rate-responsive ventricular pacemaker was implanted in all patients. The success of the procedure was confirmed 3 months later, during transitory pacemaker inhibition. Patients 1 and 3 exhibited atrial tachycardia and atrial flutter, respectively, but complete AV block was still present, with junctional escape rhythm at a rate of 40 and 45 b/min; in patient 2 atrial tachycardia with high degree AV block, and a mean ventricular rate of 75 b/min, were observed. Refinement of transcatheter ablative techniques is desirable. However, even in the present status, catheter ablation of the His bundle is an effective, low-risk procedure for patients with refractory supraventricular tachyarrhythmias.

[Asymptomatic pre-excitation. Identification of potential risk using transesophageal pacing]. / Preeccitazione asintomatica. Identificazione del rischio potenziale mediante pacing transesofageo.

Noninvasive assessment of the conducting capability of the accessory pathway (AP) in asymptomatic patients with a preexcitation ECG pattern is desirable, since life-threatening arrhythmias and sudden death may be the first manifestation of the Wolff-Parkinson-White (WPW) syndrome. To investigate whether in patients with preexcitation ECG pattern the absence of clinical arrhythmias excludes the potential for rapid ventricular responses, transesophageal atrial pacing (TAP) was performed in 11 subjects (9 male, 2 female), aged 5 to 43 years. The extrastimulus technique was used in order to define the refractory periods and in the attempt to induce reciprocating tachycardia. Incremental TAP up to the occurrence of block in the AP was instituted, and attempts to induce atrial fibrillation (AF) with rapid burst pacing were made. One to one atrioventricular conduction over the AP at progressively increased cycle lengths (CLs), and the shortest R-R interval between pre-excited beats during induced AF were evaluated. The following findings were considered predictors of potential life-threatening arrhythmias: 1) anterograde refractory period of the AP equal to or shorter than 250 ms; 2) one to one AP conduction at CLs shorter than 300 ms; 3) shortest R-R interval, during induced AF, less than 250 ms. Sustained reciprocating tachycardia could not be induced in all patients in spite of the use of the use of an aggressive stimulation protocol. The anterograde refractory period of the AP could not be defined in 9 patients. In the remaining 2 this parameter was longer than 250 ms. In 8 patients (72%), the shortest CL maintaining 1:1 AP conduction ranged from 220 to 280 ms (mean 253 +/- 19).(ABSTRACT TRUNCATED AT 250 WORDS)

[Electrophysiologic significance of the electric alternans in supraventricular tachycardia]. / Significato elettrofisiologico dell'alternanza elettrica nella tachicardia sopraventricolare.

To investigate the electrophysiologic significance of QRS alternans during narrow QRS tachycardia, transesophageal atrial pacing and recording was performed in 24 patients with a history of paroxysmal supraventricular tachycardia. Standard electrocardiograms (ECG) showed ventricular preexcitation in 15 patients and normal QRS pattern in 9. The ventriculo-atrial interval during tachycardia, as defined by means of transesophageal electrogram, allowed tentative diagnosis of the tachycardia mechanism. A 12-lead ECG was recorded either during spontaneous or induced tachycardia, as well as during transesophageal atrial pacing at increasing rates. Electrical alternans occurred spontaneously in 8 patients (33%, Group A): 5 with accessory pathway reentry (mean VA: 136 +/- 43 ms), 3 with intranodal reentry (mean VA: 48.3 +/- 43 ms). Tachycardia rate ranged between 170 and 230 b/min (mean 200.7 +/- 16). In 2 patients alternation of the QRS occurred only in the presence of a heart rate exceeding 180 and 190 b/min, respectively. The amplitude of QRS remained stable during tachycardia in 16 patients (67%, Group B): 14 with accessory pathway reentry (mean VA: 137.5 +/- 32 ms), 2 with intranodal reentry (mean VA: 45 +/- 7 ms). In this group, the tachycardia rate ranged from 150 to 210 b/min (mean 175 +/- 12). Incremental transesophageal atrial pacing up to rates equal to that of tachycardia was performed in 5 patients of Group A and in 8 of Group B. Electrical alternans could not be induced in both groups with pacing at progressively increasing rates. In contrast, the phenomenon was elicited in 2 patients of Group A when an abrupt pacing at the same rate that had showed the spontaneous occurrence of QRS alternans was instituted.(ABSTRACT TRUNCATED AT 250 WORDS)

[Transesophageal pacing in the diagnosis of accelerated atrioventricular conduction]. / Il pacing transesofageo nella diagnosi di conduzione atrioventricolare accelerata.

The term "enhanced atrioventricular nodal conduction" (EAVN) is used to indicate an electrophysiologic condition characterized by subnormal conduction delay with reduced decremental properties in the AV node, which can be responsible for rapid ventricular rates in the event of fast atrial rhythms. Although identification of such an entity usually requires definition of the AV conduction intervals, some authors have suggested that EAVN can be diagnosed, by means of atrial pacing only, when 1:1 conduction with narrow QRS complexes occurs during atrial pacing at rate higher than 200 bpm. The use of incremental transesophageal atrial pacing (TAP) as a noninvasive tool for identification of EAVN was investigated in 19 patients. Fifteen had a history of supraventricular tachyarrhythmias (11 Wolff-Parkinson-White syndrome; 2 Lown-Ganong-Levine syndrome; 1 intranodal AV reentry tachycardia; 1 sick sinus syndrome); 4 patients exhibited an electrocardiographic pattern of preexcitation without a history of tachyarrhythmias. Analysis of AV conduction at fast induced rates was hampered in 5 patients because of the easy occurrence of reciprocating tachycardia and/or atrial fibrillation during TAP, as well as because of the persistence of delta wave at cycle lengths (CL) shorter than 300 ms. Among the remaining patients, in 7 (50%, Group A), 1:1 AV conduction was present at pacing CL shorter than 300 ms. In 7 patients (50%, Group B), AV block occurred at pacing CL longer than 300 ms.(ABSTRACT TRUNCATED AT 250 WORDS)