Ventricular and Dual Chamber Pacing for Treatment of Carotid Sinus Syndrome

Thirty-nine consecutive patients with recurrent syncope and either cardioinhibitory or mixed type carotid sinus syndrome were studied to determine the efficacy of ventricular (VVI) pacing in 16, and dual chamber (DDD/DVI) in 23 patients. Only those patients affected by the isolated vasodepressor form were excluded. Follow-up lasted 12 ± 5 months. Symptoms were totally eliminated in 67% of patients and ameliorated with persistence of minor symptoms in 33%. All patients underwent an initial 2-month follow-up in the VVI mode. Evaluation of the 19 patients who remained symptomatic and the 20 who became asymptomatic with VVI pacing demonstrated that factors observed prior to pacemaker implant were related to failure of the VVI mode. These included symptomatic pacemaker effect (42% vs 0%), mixed carotid sinus syndrome (95% vs 65%), orthostatic hypotension (47% vs 15%), or ventriculoatrial conduction (68% vs 38%). In the 23 patients with dual chamber pacing, random 2 month comparisons were performed between VVI and DVI/DDD pacing. The dual chamber mode was preferred by 14 patients, none preferred the VVI mode and nine noted no difference. Comparison of the two groups found that the factors linked to DVI/DDD preference were symptomatic pacemaker effect (50% vs 0%), ventriculoatrial conduction (78% vs 44%), or orthostatic hypotension (50% vs 11 %). VVI pacing is efficacious in a high proportion of patients affected by cardioinhibitory or mixed carotid sinus syndrome. The identification of causes of VVI pacing failure allows determination of those who will benefit from VVI pacing and those who should have DVI/DDD. VVI pacing is suggested for the cardioinhihitory type with no symptomatic pacemaker effect and for the mixed type with no symptomatic pacemaker effect or orthostatic hypotension or ventriculoatrial conduction. Dual chamber pacing should be used in all other instances.     

Fourier Analysis in Patients with Different Pacing Modes

The purpose of this study was to evaluate the usefulness of phase analysis in detecting the altered activation sequence induced by different pacing modes. Radionuclide ventriculography and planar gated blood pool scintigraphy were performed at rest in 56 patients with different pacemakers. This method permitted us to localize the pacemaker impulse site in the right ventricle and its diffusion in the heart. In patients with VVI pacemaker, this technique showed an evident asynchronism of contraction and relaxation of each ventricle and the standard deviation of phase angle (sigma), calculated by computer, is greater during pacing than sinus rhythm for left (LV) and right (RV) ventricles (LV sigma: 17 degrees +/- 4 vs 11 degrees +/- 3, less than 0.001; RV sigma: 31 degrees +/- 7 vs 14 degrees +/- 4, P less than 0.001). In the patients with VVI rate responsive pacemakers, the LV sigma changed from 18.5 +/- 3 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.001, while the RV sigma changed from 30 degrees +/- 8 to 14 degrees +/- 4, P less than 0.001. Instead in the patients with DDD pacemakers, the LV sigma changed from 15.5 degrees +/- 2 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.05, while the RV sigma changed from 29.1 degrees +/- 6 to 14 degrees +/- 4, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrapatient Comparison Between Chronic VVIR and DDD Pacing 'In Patients Affected by High Degree AV Block Without Heart Failure

MENOZZI, C., ET AL.: Intrapatient Comparison Between Chronic VVIR and DDD Pacing in Patients Affected by High Degree AV Block Without Heart Failure. In patients affected by high degree AV block without preexisting congestive heart failure there is no definite demonstration that DDD pacing gives real clinical advantages in respect to VVIR pacing. We performed an intrapatient, long-term study between the two pacing modes in 14 high degree AV block patients, using the Medtronic Synergyst 7027 dual chamber pacemaker, who could be programmed alternatively in DDD or VVIR mode. After a 4-week run-in period following the pacemaker implant, patients completed a randomized, double-blind, cross-over study to compare the effect of 6-week period VVIR and DDD pacing on symptoms and cardiovascular parameters. A semiquantitative score scale was used to quantify the symptoms of general well-being, palpitations, dizziness, pulsating sensation in the neck or abdomen, shortness of breath at rest and during effort, chest pain, and NYHA classification. The sum of symptom scores was 10.4 ± 6.7 in VVIR period and 4.6 ± 2.7 in DDD period (p < 0.001); five patients (36%) crossed over early from VVIR to DDD because of intolerable symptoms; overall, eight patients preferred the DDD mode and no one preferred the VVIR. Cardiac output at rest (echo-Doppler method) was 4.7 ± 1.4 versus 5.7 ± 1.6 liter/min (p < 0.01), body weight was 65.9 ± 6.6 versus 64.9 ± 6.1 kg (p < 0.02), atrial natriuretic peptide was 236 ± 112 versus 198 ± 110 pg/mL (p < 0.01), respectively, during VVIR and DDD modes. Effort tolerance was similar with the two modes of pacing (68 ± 15 vs 70 ± 18 watt/min). In conclusion, hemodynamic advantages of atrial synchronization reflect a better quality of life for the patients even if an individual variability exists.     

Assessment of VVI Diagnostic Pacing Mode in Patients with Cardioinhibitory Carotid Sinus Syndrome

In this study, we used Holter pacemakers in a group of 13 patients affected by severe carotid sinus syndrome in order to evaluate its evolution. All the patients had one to three syncopal episodes and frequent other symptoms such as fainting, dizziness, lightheadedness and pre-syncope interferring with their daily activity so that pacemaker therapy was considered necessary. Patient selection criteria were: presence of the isolated cardioinhibitory type, absence of associated sinus dysfunction and absence of symptomatic WI pacemaker effect. All the patients received a Micropacer 1 device; among special functions, bradycardia events counter was activated and programmed so that each sequence of three consecutives beats at a cycle length 1.5 sec (i.e., 4.5 sec total interval) could he recognized and stored in its memory. The follow-up lasted 13±7 months. Brady events occurred in eight out of 13 patients (62%), during this period. Syncope and major symptoms disappeared in ail the patients; mild dizziness recurred rarely in two patients and were not linked to brady-events recording. In conclusion, disappearance of severe symptoms observed after pacemaker implant in cardioinhibitory carotid sinus syndrome seems to depend from pacing therapy, in most cases, yet from the benign natural course of the disease in some other cases.     

The Effect of Exogenous Adenosine in Patients with Neurally-Mediated Syncope and Sick Sinus Syndrome

The effects of a 20-mg IV, bolus of adenosine 5'triphosphate (ATP) on the heart rhythm was studied in 79 patients affected by neurally-mediated syncope (26 cases) or sick sinus syndrome (22 cases) or both syndromes (31 cases) and in 31 healthy control subjects in order to examine the sensitivity of cardiac purinoceptors in such circumstances. During ATP infusion, the sinus cycle lengthened to > 2 seconds in no control, in 1 (4%) patient with neurally-mediated syncope, in 5 (23%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated and sick sinus syndromes (P = 0.01). Atrioventricular block occurred in 14 (45%) of controls, in 10 (38%) patients with neurally-mediated syncope, in 4 (18%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated syncope and sick sinus syndrome (n.s.). Thus, exogenous ATP exerts different effects on patients with neurally-mediated syncope and patients with sick sinus syndrome. In fact, intrisic disease of the sinus node is necessary to modulate an abnormal adenosine-mediated sinus arrest, whereas patients affected by neurally-mediated syncope alone show a normal sensitivity to the drug administration. The effect of ATP on atrioventricular conduction is greater than that on sinus node and is of similar magnitude in patients and controls; thus the clinical meaning of ATP induced atrioventricular block remains uncertain.     

Solid-phase synthesis of the native sequence of horse heart cytochrome c-(66–104)-nonatriacontapeptide and of a C-terminal carboxyamide analog selectively modified at Met-80

The peptide corresponding to the (66–104) sequence of horse heart cytochrome c and its carboxyamide analog, selectively modified at the critical Met⁸⁰ residue, have been synthesized by stepwise solid-phase methods on PAM and BHA resins respectively. The correctness of the growing peptide chain as well as the homogeneity of the final products have been monitored by several analytical methods including quantitative Edman degradation. After HF cleavage both peptides were purified by semipreparative HPLC. The overall yields were 24% for the native (66–104) and 10% for the carboxyamide analog. The homogeneity of the purified synthetic peptides have been determined by different criteria including HPLC, amino acid composition, Edman degradation, electrophoresis, and tryptic peptide mapping. The synthetic fragments have been utilized for preliminary semisynthesis experiments with the native [Hse〉⁶⁵](1–65)H heme-sequence.     

Extremely fast hydrogen exchange of ribonuclease-(1–118) as compared with native RNase A and its implication for the conformational energy state

RNase-(1–118) containing native disulfide bonds is similar in fold to native RNase A but not of lowest Gibbs energy as compared with the isomers containing non-native disulfide bonds. The present n.m.r. studies have indicated a dramatic increase in the exchange rate of all of the ‘protected’ amide protons of RNase-(1–118) over RNase A. A calculation shows a large increase in the rate of ‘opening’ of the structure. The exchange rate of the protected amide protons of RNase-(1–120) is slower than RNase-(1–118) but much faster than RNase A. Binding with a synthetic complementing fragment (114–124) markedly reduces the exchange rate of 20 to 25 amide protons of RNase-(1–118). It has previously been shown that binding with a complementing fragment of RNase-(1–118) generates a lowest Gibbs energy state. Thus, using available thermodynamic information for interpretation, we suggest that a) removal of six carboxy terminal residues of RNase A would disrupt coupling between these residues and those distant in the structure (loss of extra stabilizing energy), b) this would, in turn, alter the enthalpy-entropy compensation in such a way that the magnitude of Gibbs energy change favoring folding is significantly reduced without a large change of fold and c) in this activated state the molecule would be highly motile.     

The Replacement of the Ascending Aorta and Aortic Valve with a New Design Composite Graft: A Six-Year Experience

The problems encountered in coronary artery reattachment when the ascending aorta and aortic valve are replaced with a composite graft induced Gallucci and one of the authors to develop a new aortovalvular prosthesis in clinical practice. The unique transverse ovoidal shape of this graft is intended to conform to the natural aortic root and facilitate the coronary anastomoses and minimize bleeding. We present our 6-year experience with 56 patients operated upon with this prosthesis. In all patients we were able to connect the coronary arteries directly to the graft without complications including hemorrhage or distortion of the coronary ostia. The survivors were evaluated with chest X ray, two-dimensional echocardiography, and conventional or digital subtraction angiography to detect the presence of pseudoaneurysms at the site of the coronary anastomosis, reported by others that have used the composite graft technique. The notable absence of this complication in our patients at a mean follow-up of 41 months (range 3-71) documents that this ovoidal composite graft is a reliable tool in the treatment of aortic root pathology.     

Visualization of Pattern Flow in Abdominal Arteries by Transgastric Echocardiography After Aortic Dissection Repair

The persistence of false lumen after surgical repair of aortic dissection is frequent. This event has a negative impact on the prognosis and is secondary to the persistence of unrepaired entry sites and of dissected major aortic branches. We describe three cases in which visualization of a dissected celiac trunk with an anomalous flow pattern was possible with transesoghageal echocardiography. Two of these cases died in the early postoperative period and the echo findings were confirmed at necropsy. We suggest that visualization of anomalous pattern flow in the celiac trunk is of prognostic relevance because it plays a major role in mantaining the false lumen persistence and, therefore, should be part of the routine examination after surgical repair of aortic dissection.     

Molecular Biology of the Long QT Syndrome: Impact on Management

The long QT syndrome (LQTS) is a familial disease characterized by prolonged ventricular repolarization and high incidence of malignant ventricular tachyarrhythmias often occurring in conditions ofadrenergic activation. Recently, the genes for the LQTS linked to chromosomes 3 (LQT3), 7 (LQT2), and 11 (LQTl) were identified as SCN5A, the cardiac sodium channel gene and as HERG and KvLQTl potassium channel genes. These discoveries have paved the way for the development of gene-specific therapy for these three forms of LQTS. In order to test specific interventions potentially beneficial in the molecular variants of LQTS, we developed a cellular model to mimic the electrophysiological abnormalities of LQT3 and LQT2. Isolated guinea pig ventricular myocytes were exposed to anthopleurin and dofetilide in order to mimic LQT3 and LQT2, respectively. This model has been used to study the effect of sodium channel blockade and of rapid pacing showing a pronounced action potential shortening in response to Na⁺channel blockade with mexiletine and during rapid pacing only in anthopleurin-treated cells but not in dofetilide-treated cells. Based on these results we tested the hypothesis that QT interval would shorten more in LQT3 patients in response to mexiletine and to increases in heart rate. Mexiletine shortened significantly the QT interval among LQT3 patients but not among LQT2 patients. LQT3 patients shortened their QT interval in response to increases in heart rate much more than LQT2 patients and healthy controls. These findings suggest thatLQT3 patients are more likely to benefit from Na⁺ channel blockers and from cardiac pacing because they are at higher arrhythmic risk at slow heart rates. Conversely, LQT2 patients are at higher risk to develop syncope under stressful conditions, because of the combined arrhythmogenic effect of cate-cholamines with the insufficient adaptation of their QT interval. Along the same line of development of gene-specific therapy, recent data demonstrated that an increase in the extracellular concentration of potassium shortens the QT interval in LQT2 patients suggesting that intervention aimed at increasing potassium plasma levels may represent a specific treatment for LQT2. The molecular findings on LQTS suggest the possibility of developing therapeutic interventions targeted to specific genetic defects. Until definitive data become available, antiadrenergic therapy remains the mainstay in the management of LQTS patients, however it may be soon worth considering the addition of a Na + channel blocker such as mexiletine for LQT3 patients and of interventions such as K⁺ channel openers or increases in the extracellular concentration of potassium for LQTl and LQT2 patients.