Alterations in the expression of genes related to contractile function and hypertrophy of the left ventricle in chronically paced patients from the right ventricular apex.

AIM: Long-term right ventricular apical (RVA) pacing may lead to left ventricular (LV) remodelling and heart failure. This study assessed changes in the expression of genes regulating LV contractile function and hypertrophy, after permanent RVA pacing and investigated whether such changes proceed or even predict LV remodelling. METHODS AND RESULTS: We enrolled 52 consecutive patients (age 79.1 ± 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic indications: Group A, 24 individuals with atrioventricular conduction disturbances and group B, 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase decreased at 3, 6, and 12 months' follow-up, while α-myosin heavy chain (MHC) decreased and ß-MHC increased until 6 months follow-up. In this group, 25% of patients demonstrated significant LV remodelling. At 4 years, LV end-systolic diameter increased from 29.67 ± 3.39 mm at baseline to 35.38 ± 4.22 mm, LV end-diastolic diameter increased from 50 ± 4.95 to 56.71 ± 5.52 mm, and ejection fraction declined from 63.04 ± 10.22 to 52.83 ± 10.81%. Early alterations in gene expression were associated with a deterioration in LV function and geometry that became apparent months later. In group B, echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no statistically significant changes. CONCLUSIONS: Permanent RVA pacing in patients with preserved ejection fraction is associated with alterations in the expression of genes regulating LV contractile function and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and are associated with LV remodelling that becomes evident in the long term.

Biventricular pacing in paced patients with normal hearts.

Right ventricular apical (RVA) stimulation, although beneficial in the treatment of symptomatic bradycardia, has proven detrimental in a substantial percentage of pacemaker recipients, leading to iatrogenic deterioration of left ventricular structure and function. Alternative right ventricular pacing sites appeared advantageous but their superiority has not been proven. Biventricular stimulation is effective in reducing ventricular dyssynchrony in subgroups of heart failure patients, improving their functional capacity, morbidity, and mortality. Therefore, it seems logical that this pacing strategy, by eliminating ventricular dyssynchrony, could play an important role in preventing the deleterious effects of chronic RVA stimulation in patients with normal hearts who undergo cardiac pacing for bradycardia indications. Preliminary investigations have yielded encouraging results, but further studies with harder endpoints such as quality of life, morbidity, and mortality are necessary to clarify the potentially advantageous effect of biventricular stimulation in paced patients with normal hearts.

Appropriate management of syncope in a patient with hypertrophic cardiomyopathy: rationale behind long-term cardiac rhythm monitoring.

We describe the case of a patient with hypertrophic cardiomyopathy who had recurrent syncopal episodes, the cause of which remained unexplained despite a thorough evaluation. Two years after his first evaluation, an implantable loop recorder revealed asymptomatic episodes of advanced second degree atrioventricular block while the patient was awake. Although a permanent pacemaker was implanted, the patient continued to suffer syncopal episodes, during which the pacemaker recorded episodes of ventricular tachycardia. Accordingly, the device was upgraded to an implantable cardioverter-defibrillator.

Angiotensin II type 1 receptor inhibition is associated with reduced tachyarrhythmia-induced ventricular interstitial fibrosis in a goat atrial fibrillation model.

BACKGROUND: Using a goat animal model, we tested the hypothesis that angiotensin-II inhibition reduces fibrotic degeneration of both the atrial and ventricular myocardium as well as AF induction susceptibility. METHODS: We studied three groups of five goats over a 6-month period. The study animals in the first two groups were implanted with a pacemaker capable of maintaining AF with burst pacing. Additionally, in one group, goats were administered candesartan (AF+candesartan group). The third group (SR group) of animals served as control. Animals were tested for AF induction on day 0, 1, 30, 90 and 180. A "Vulnerability Index" (VI) for AF induction was calculated, defined as the ratio of total time in AF per number of bursts needed to induce sustained AF, in each session. At the end of the study, all four heart chambers were examined and fibrosis quantified. RESULTS: Both AF goat groups developed cardiomegaly due to tachy-cardiomyopathy. Although, the VI was significantly increased in AF group over time (28.8+/-43 to 284.7+/-291, p=0.045), this was not the case for AF+candesartan group (30.3+/-40 to 170.8+/-243, p=0.23). Histology revealed a significant increase of fibrous tissue in goats with induced AF, noticeable in all four heart chambers, compared to controls. However, the degree of fibrosis was significantly lower in AF animals on candesartan. CONCLUSIONS: Our study demonstrated a beneficial effect of angiotensin II inhibition on tachyarrhythmia-induced ventricular fibrosis. It is also consistent with previous studies indicating a reduction in burst-induced AF susceptibility in goats and confirms the favorable effects in atrial structural remodeling.

Continuous positive airway pressure therapy lowers vagal tone in patients with obstructive sleep apnoea-hypopnoea syndrome.

INTRODUCTION: Sleep apnoea, which constitutes a major social problem because of its high prevalence and its emerging association with cardiovascular morbidity and mortality, is known to affect autonomic nervous system activity. We assessed the hypothesis that treatment of sleep apnoea patients with continuous positive airway pressure (CPAP) alters the indices of heart rate variability (HRV) that reflect sympathetic and parasympathetic autonomic nervous system activity. METHODS: We studied 26 patients (18 men, aged 49.2 +/- 7.6 years) with obstructive sleep apnoea-hypopnoea syndrome. In all patients, a 24-hour Holter recording was obtained one week before initiation of CPAP treatment and another one two months later. From these recordings we assessed the time domain indices of HRV (pNN50, rMSSD, SDNN, SDANN, SD) during the day (08:00-23:00) and during the night hours (23:00-08:00) as well as their post-treatment changes. The same HRV indices were also assessed in a group of 19 age and sex matched controls, without sleep apnoea. RESULTS: No significant differences in the HRV indices were observed during the daytime hours, while during the night both pNN50 and rMSSD were significantly higher in patients compared to controls (19.5 +/- 12.5 vs. 13.8 +/- 9.7, p=0.001, for pNN50 and 54.7 +/- 23.1 vs. 44.0 +/- 15.9, p=0.001, for rMSSD, for patients and controls respectively). No such differences were observed in any of the monitored indices following CPAP treatment. CONCLUSIONS: The indices that reflect parasympathetic activity are increased during the night in patients with obstructive sleep apnoea syndrome. CPAP treatment reduces the night time vagal indices of HRV to resemble those of normal controls. The reduction of parasympathetic activity may be one of the mechanisms responsible for the alleviation of bradyarrhythmic episodes following the initiation of CPAP therapy.

Atrial overdrive pacing for the obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: The role of atrial overdrive pacing (AOP) in sleep apnea remains uncertain. We prospectively evaluated the effect of AOP after 24 hours and after one month in patients with the obstructive sleep apnea-hypopnea syndrome and compared it with the use of nasal continuous positive airway pressure (n-CPAP). METHODS: We studied 16 patients with a moderate or severe case of the obstructive sleep apnea-hypopnea syndrome (baseline mean apnea-hypopnea index, 49) and normal left ventricular systolic function in whom a dual-chamber pacemaker had been implanted. After 48 hours, the patients were randomly assigned to AOP (pacing at 15 bpm above the spontaneous mean nocturnal heart rate) or backup atrial pacing (pacing at a heart rate below 40 bpm); the latter group began n-CPAP therapy one day later. After one month, the two groups switched therapies and were followed for an additional month. Polysomnographic studies were performed at baseline, on the first night after randomization, at crossover, and at the end of the study. RESULTS: During AOP, no significant changes were observed in any of the respiratory variables measured. The change in the apnea-hypopnea index at one month with AOP was +0.2 (95 percent confidence interval, -2.7 to +2.3; P=0.87). In contrast, all variables improved significantly after one month of n-CPAP (change in the apnea-hypopnea index, -46.3; 95 percent confidence interval, -56.2 to -36.5; P<0.001). CONCLUSIONS: Nasal continuous positive airway pressure therapy is highly effective for the treatment of the obstructive sleep apnea-hypopnea syndrome, whereas AOP has no significant effect.

Ventricular special defect in the elderly: an uncommon clinical entity.

Ventricular septal defect (VSD) is the most frequent congenital heart disease in adults, with equal distribution in both sexes, and has an incidence of about 20% in children. In adults congenital VSDs represent about 10% of all cases and the mortality at age 60 is around 75%. For elderly patients >80 years old only one living case has been reported previously. Here we describe an 86-year-old patient, totally asymptomatic, with a muscular type of VSD that showed interesting, canal-like echocardiographic images.

Autonomic nervous system changes in vasovagal syncope: is there any difference between young and older patients?

Spectral analysis of heart rate variability was used to compare the changes in autonomic function during tilting in young and older patients with vasovagal syncope. Twenty-four young (age 28 +/- 8 years) and 31 older (56 +/- 5 years) patients with unexplained syncope and a positive tilt test and 25 controls (age 48 +/- 12 years) were included in the study. Frequency-domain measurements of the low (LF) (0.06-0.15 Hz) and high (HF) (0.15-0.40 Hz) frequency bands and the ratio of LF to HF were computed from Holter recordings for 4-minute intervals before and immediately after tilting and just before the end in all groups. Syncopal patients showed a different pattern of response to tilting from controls in all spectral indexes. Young and older patients showed the same pattern of changes in all measurements, even though certain differences were observed. The LF after tilting reduced more in the older (-20 +/- 7% vs -14 +/- 5%, P < 0.001), while HF reduced more in young patients (-17 +/- 8% vs -8 +/- 3%, P < 0.001). Young patients showed mainly a cardioinhibitory type (71%) of response whereas a vasodepressor type response predominated (68%) in the older patients. The autonomic nervous system appears to play an important role in the pathophysiological mechanism of vasovagal syncope. This role is similar in young and in older patients and this should be taken into account in the therapeutic approach to the condition. Specific differences between age groups may be related to the type of vasovagal syncope.

Severe bradyarrhythmias in patients with sleep apnoea: the effect of continuous positive airway pressure treatment: a long-term evaluation using an insertable loop recorder.

AIM: In this new era of insertable loop recorders, we studied obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients in order to evaluate their arrhythmias and the beneficial effect of Continuous Positive Airway Pressure treatment (CPAP), over a long-term period. METHODS AND RESULTS: We enrolled 23 patients (16 men, 50 +/- 11 years) with moderate and severe OSAHS. In all patients, an insertable loop recorder capable of monitoring the heart rhythm for 16 months was implanted. Cardiac pauses >3 s and bradycardic episodes <40 bpm during a 2-month period before, and for 14 months after, the CPAP application, were noted. In each period, the patients underwent two 24-h Holter recordings. Before treatment, 11 patients (47%) revealed severe cardiac rhythm disturbances, mostly nocturnal. Holter recordings showed disturbances in only 3 (13%) patients (P=0.039), those in whom the insertable loop device had recorded frequent episodes. Eight weeks after the initiation of treatment, the total number of the recorded episodes tended to decrease while, during the last 6 months of the follow-up, no episodes were recorded. CONCLUSION: Approximately half of OSAHS patients evidence severe cardiac rhythm disturbances, which are significantly reduced by CPAP. Holter recordings seem unable to precisely describe the incidence of severe brady-arrhythmias and the effect of treatment.

Late left ventricular diastolic flow propagation velocity determined by color M-mode Doppler in the assessment of diastolic dysfunction.

BACKGROUND: Early color M-mode Doppler flow propagation (Ep) through the left ventricle (LV) has been proposed as a useful noninvasive index for assessing LV relaxation, whereas data concerning late velocity propagation (Ap) is lacking. METHODS: We studied 51 patients with delayed relaxation (group I) and 50 with pseudonormal filling pattern (group II). Another 51 aged-matched healthy persons served as the control group. RESULTS: Patients showed increased left atrial dimensions, atrial wave of the pulmonary vein flow, and Ap, and reduced LV ejection fraction, Ep, and Ep/Ap ratio compared with the control group. Patients in group II revealed increased left atrial dimensions (P =.001), atrial wave of the pulmonary vein flow (P <.001), and Ep/Ap ratio (P <.001), and reduced LV ejection fraction and Ap (P <.001) compared with group I. Regression analysis showed that the strongest independent variable distinguishing normal from pseudonormal filling pattern was the Ep/Ap ratio. CONCLUSION: Ap evaluation offers a new diagnostic diastolic index, especially in the field of the pseudonormal pattern where the separation from normal is difficult.

Left ventricular mechanics and myocardial blood flow following restoration of normal activation sequence in paced patients with long-term right ventricular apical stimulation.

STUDY OBJECTIVES: Asynchronous ventricular activation, as induced by ventricular pacing, is known to affect left ventricular (LV) systolic and diastolic function and myocardial blood flow. However, it is not clear whether the long-term disturbances it causes are reversible after the restoration of the normal ventricular activation sequence. DESIGN: In this study, we used the conductance catheter method and a Doppler guidewire to assess the changes in LV mechanics, and correspondingly in myocardial blood flow, after the restoration of the normal ventricular activation sequence in patients with long-term right ventricular apical pacing. PATIENTS: Sixteen patients (mean [+/- SD] age, 61 +/- 11 years; 9 men) with right ventricular apical stimulation and complete ventricular pacing capture for a very long period were studied. In eight patients, we analyzed pressure-volume loops before and immediately after the restoration of the normal ventricular activation sequence, and in the remaining eight patients the myocardial blood flow and flow reserve were analyzed. MEASUREMENTS AND RESULTS: End-systolic elastance (Ees) [5.503 +/- 0.6 vs 4.287 +/- 0.28 mm Hg/mL, respectively; p = 0.003] and its ratio to effective arterial elastance (1.63 +/- 0.51 vs 2.00 +/- 0.64, respectively; p = 0.009), which are indexes of systolic function and ventriculoarterial coupling, respectively, improved significantly after restoration of the normal ventricular activation sequence. Indexes of diastolic function and the predicted myocardial oxygen consumption (MO(2)) showed no clear change. Coronary flow in the dominant coronary artery increased significantly (46.55 +/- 14.12 vs 71.55 +/- 27.53 mL/min, respectively; p = 0.002), while the coronary flow reserve in the same artery decreased (3.5 +/- 1.0 vs 2.6 +/- 0.5, respectively; p = 0.008). CONCLUSIONS: The restoration of a normal activation sequence after long-term ventricular asynchrony enhances acutely contractile function without affecting MO(2). These changes in LV function do not appear to have causal relationships with myocardial blood flow changes.

Myocardial perfusion and adrenergic innervation in patients with RBBB and LAfB: the effect of altering the activation sequence with right ventricular apical pacing.

The aim of this study was to investigate myocardial perfusion and adrenergic innervation in patients with intraventricular conduction disturbances and to detect any changes caused by alteration of the ventricular activation sequence as a result of right ventricular apical pacing. We studied 15 patients with right bundle branch block (RBBB) and left anterior fascicular block (LAFB), while 15 healthy individuals served as controls. All patients underwent planar and single-photon emission computed tomography (SPECT) myocardial imaging after intravenous infusion of 5mCi 123I-metaiodobenzylguanidine (123I-MIBG) and a SPECT thallium201 myocardial perfusion study before and 3 months after pacemaker implantation. The heart to mediastinum ratio was calculated during the 123I-MIBG study in order to assess the global cardiac sympathetic activity and was significantly smaller in patients than in controls (P < 0.001). Patients with RBBB and LAFB revealed regional adrenergic innervation defects, mostly in the inferior and posterior walls. After a medium-term pacing period, a redistribution of 123I-MIBG uptake was detected, with aggravation of adrenergic innervation defects in the apical and posterior walls and amelioration in septal and anterior walls. Five patients showed perfusion defects that remained unchanged after pacing. Two others displayed mild myocardial perfusion defects that did not exist before pacing. In conclusion, patients with RBBB and LAFB reveal global and regional disturbances of myocardial adrenergic innervation, which shows redistribution as a result of the altered propagation of the ventricular electrical activation. To a smaller degree these patients reveal myocardial perfusion disturbances in which pacing has a limited medium-term effect.

Electrocardiographic appearance of old myocardial infarction in paced patients.

This study evaluated the possibility of diagnosing chronic myocardial infarction in the presence of the pacing electrocardiogram. Forty-five patients with known myocardial infarction (anterior 23, inferior 22) and 26 healthy controls were studied. After coronary angiography, pacing was applied from the right ventricular apex, and the sensitivity, specificity, and average diagnostic accuracy of five criteria on the paced electrocardiogram were assessed: (1) Notching 0.04 second in duration in the ascending limb of the S wave of leads V3, V4, or V5 (Cabrera's sign); (2) Notching of the upstroke of the R wave in leads I, aVL, or V6 (Chapman's sign); (3) Q waves > 0.03 second in duration in leads I, aVL, or V6; (4) Notching of the first 0.04 second of the QRS complex in leads II, III, and aVF; (5) Q wave > 0.03 second in duration in leads II, III, and aVF. The most sensitive criteria, for anterior and inferior myocardial infarctions were Cabrera's and Chapman's (91.1 and 86.6%, respectively). All criteria had low specificity (range 42.3-69.2%). The combination of Cabrera's and Chapman's sign decreased the sensitivity to 77.7%, but increased specificity to 82.2%. The sensitivity and specificity of all the criteria were independent of the myocardial infarction site. In paced patients, the application of electrocardiographic criteria, and especially the combination of Cabrera and Chapman, provides useful clinical information in recognizing prior myocardial infarction but not in assigning the specific infarct site.

Anomalous collateral from the coronary artery to the affected lung in a case of congenital absence of the left pulmonary artery: effect on coronary circulation.

A case of congenital absence of the left pulmonary artery, in which perfusion of the affected lung was accomplished via an arterial shunt from the circumflex coronary artery, is discussed. Data from myocardial perfusion scintigraphy showed that myocardial perfusion was unaffected by the existence of the shunt, largely because the flow through the shunt occurred mainly during systole.