Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

[Is resting heart rate a cardiovascular risk factor?]. / Ist die Ruheherzfrequenz ein kardiovaskulärer Risikofaktor?

During recent years, resting heart rate was not considered as a cardiovascular risk factor. However, new evidences have showed that resting heart rate is an important prognostic factor for sudden cardiac death and heart failure in the general population, and especially among patients with known cardiac disease. Interestingly, resting heart rate not only predicts cardiac mortality but also all-cause mortality. The most common pathophysiological explanation is related to the fact that increased heart rate increases myocardial oxygen consumption and in parallel reduces coronary blood flow (reduction in the diastolic duration).

Activation of electrical triggers of atrial fibrillation in hyperthyroidism.

CONTEXT: A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved. OBJECTIVE: Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease. PATIENTS AND DESIGN: Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels. MAIN OUTCOME MEASURES: The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up. RESULTS: SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability. CONCLUSION: Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.

[Ventricular tachycardia--etiology, mechanisms and therapy]. / Kammertachykardien--Atiologie, Mechanismen, Therapie.

Prevention and therapy of cardiovascular diseases have undergone enormous changes over the last decades. However, ventricular tachycardias (VT) still pose a major problem in a number of cardiac patients. Analysis of the etiology and mechanism of the tachycardia is of paramount importance for initiation of specific therapies. The morphology of VTs on the surface ECG can be either polymorphic or monomorphic. Polymorphic VTs have a constantly changing QRS-morphology due to the variable ventricular activation, without specific origin. This kind of VT is mainly caused by an acute, often reversible condition, such as ischemia or QT-prolongation. These VTs are potentially malignant, they cannot be treated by catheter ablation. In contrast, monomorphic VTs have a constant QRS-morphology, indicative of repetitive ventricular depolarisation in the same activation sequence. This kind of VT is either caused by focal abnormal activity (triggered activity, automaticity, micro-reentry) or by an arrhythmogenic substrate (macro-reentry). Focal idiopathic VTs usually have a benign prognosis and catheter ablation is potentially curative. The majority of ventricular arrhythmias, however, are substrate-related reentry tachycardias, most commonly based on an infarct scar Therapy of first choice for these patients is the treatment with an implantable Cardioverter/Defibrillator (ICD). Catheter ablation is indicated in case of drug refractory recurrent VTs triggering repeated ICD therapies. The different therapeutic strategies are not alternative but complementary options in many patients.

[Radiofrequency catheter ablation of ventricular tachycardias]. / Radiofrequenz-Katheterablation ventrikulärer Tachykardien.

Management of patients with ventricular tachycardia (VT) is often difficult. Drug therapy is often ineffective. Implantable cardioverter defibrillators (ICDs) can terminate VT episodes but do not prevent them. Radiofrequency (RF) catheter ablation can suppress arrhythmias in selected patients. However, the procedure is often challenging and success rates lower than for ablation of supraventricular tachycardias. The mapping and ablation approach depends on the VT mechanism. Monomorphic VT in patients without structural heart disease is referred to as idiopathic and has a focal origin. These VTs can be abolished by ablation in most of the patients. In VT due to reentry within an area of scar from an old myocardial infarction or cardiomyopathic process, critical parts of the circuit may be difficult to localize, rendering RF ablation challenging. In patients with monomorphic VT, prevention of VT recurrence can be achieved in 55% to 80% of patients. Multiple morphologies of VTs and circuits that are located deep in the endocardium are common problems that reduce efficacy. Furthermore, mapping to identify target regions for ablation can be more difficult if VT is rapid and not tolerated, or not inducible. Recently, multisite mapping of the arrhythmia substrate during sinus rhythm or multisite activation mapping of a few VT beats were shown to be effective for ablation of these "unmappable VTs". Bundle branch reentry tachycardia occur in patients with nonischemic cardiomyopathies, mostly valvular heart disease and can be successfully abolished with RF ablation of the right bundle. However, some of these patients may develop recurrences due to other types of VT. Recent technical developments have increased efficacy and simplified the approach of RF ablation of VT in patients with structural heart disease. However, long-term efficacy is not accurately predictable and implantation of an ICD is mandatory in most of the patients with severely depressed left ventricular function.

Wide complex tachycardia and congenital heart disease.

We present a patient with congenital heart disease and haemodynamically poorly tolerated wide QRS tachycardia. Differential diagnosis and therapy are discussed. After the patient underwent heart transplantation, and the substrates for ECG abnormalities and arrhythmias were demonstrated in the explanted heart.

Increased central body fat deposition precedes a significant rise in resting blood pressure in male offspring of essential hypertensive parents: a 5 year follow-up study.

OBJECTIVES: As long as offspring of essential hypertensive parents (OHyp) are lean, their blood pressure usually remains within normal limits. The mechanism(s) transforming this 'genetically dysregulated normotension' into hypertension are unclear. We hypothesized that OHyp are not only genetically prone to develop hypertension, but may also have a particular propensity to accumulate central body fat. DESIGN: A 5-year follow-up cohort study. SETTING: University Hospital in Switzerland. PARTICIPANTS: Seventeen young (25 +/- 1 years, mean +/- SD), lean healthy normotensive male OHyp and 17 age- and sex-matched offspring of normotensive parents (ONorm) paired for baseline blood pressure with the OHyp. MAIN OUTCOME MEASURES: Resting and exercise blood pressure, body weight, body mass index (BMI) and waist-to-hip ratio were assessed at baseline and after 5 years. RESULTS: At baseline, body weight, BMI, waist-to-hip ratio and blood pressure did not differ significantly between OHyp and ONorm. At follow-up, body weight was increased in both groups (from 73.9 +/- 6.0 to 77.7 +/- 8.1 kg in OHyp, P = 0.008, and from 71.5 +/- 6.9 to 73.5 +/- 6.6 kg in ONorm, P = 0.03). BMI followed a similar pattern. In contrast, waist-to-hip ratio increased in OHyp (from 0.84 +/- 0.03 to 0.87 +/- 0.03, P = 0.012), but not in ONorm (from 0.84 +/- 0.03 to 0.84 +/- 0.04, P = 0.79) and was therefore higher in OHyp at follow-up (P = 0.011, OHyp versus ONorm). Peak systolic blood pressure during dynamic exercise also rose at 5 years in the OHyp (from 182 +/- 10 to 214 +/- 17 mmHg, P = 0.0001) while resting systolic blood pressure only tended to do so (from 121 +/- 7 to 128 +/- 12 mmHg, P = 0.07). In ONorm, resting and peak dynamic exercise systolic blood pressure remained unchanged (119 +/- 11 versus 121 +/- 9 mmHg, baseline versus follow-up, P = 0.40, and 186 +/- 12 versus 196 +/- 22 mmHg, P = 0.10, respectively). Thus, systolic peak exercise blood pressure was significantly (P = 0.014) elevated at follow-up in OHyp compared to ONorm, while resting systolic blood pressure only tended (P = 0.06) to do so. CONCLUSIONS: Initially lean normotensive OHyp have a disparate long-term course of central body fat as compared to ONorm. Thus, OHyp are not only genetically prone to develop hypertension, but they also have a particular propensity to accumulate central body fat, even before a distinct rise in resting blood pressure occurs. The exaggerated blood pressure response to exercise observed at follow-up in the OHyp represents another marker that confers them a greater risk of developing future hypertension.

Radial artery compliance in response to mental stress in normotensive offspring of hypertensive parents.

OBJECTIVES: Compared to normal subjects hypertensive patients have an increased radial artery isobaric distensibility, contrasting with a decrease in elasticity of large arteries and systemic compliance. To address the question whether elasticity is increased in response to long-standing elevated blood pressure or is present at an early stage of the disease, we compared normotensive offspring of hypertensive parents with control subjects. Furthermore, enhanced sympathetic response to mental stress was demonstrated in individuals predisposed to hypertension and might contribute to the elevation of blood pressure via a peripheral mechanism. Thus, an abnormal vasoconstrictive response of the radial artery to psychological stress was sought in these subjects. DESIGN: The geometry and the elastic porperties of the radial artery were assessed in normotensive offspring of hypertensive and normotensiven parents at baseline and during mental stress. METHODS: A high-precision echo-tracking ultrasound device was combined with photoplethysmography for continuous measurement of radial artery diameter and isobaric distensibility in 18 normotensive offspring of parents with essential hypertension and 18 control subjects under resting conditions and during a 3-minute mental stress test. RESULTS: Baseline arterial distensibility and compliance were comparable in offspring of hypertensive and normotensive parents. During mental stress, blood pressure and heart rate increased similarly in both groups. Adrenergic activation did not alter the elastic properties of the radial artery in the individuals with a genetic predisposition to essential hypertension. CONCLUSIONS: There was no alteration in elastic properties of the radial artery in normotensiven individuals at genetic risk to develop arterial hypertension. Furthermore, mental stress did not abnormally increase the vascular tone of this medium-sized muscular artery in these subjects as compared to controls. This indicates that functional and/or structural vascular alterations do not precede a distinct rise in blood pressure or abnormal blood pressure reactivity in subjects prone to develop essential hypertension.

Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping.

BACKGROUND: Extensive lines of radiofrequency (RF) lesions through infarct (MI) can ablate multiple and unstable ventricular tachycardias (VTs). Methods for guiding ablation that minimize unnecessary RF applications are needed. This study assesses the feasibility of guiding RF line placement by mapping to identify a reentry circuit isthmus. METHODS AND RESULTS: Catheter mapping and ablation were performed in 40 patients (MI location: inferior, 28; anterior, 7; and both, 5) with an electroanatomic mapping system to measure the infarct region and ablation lines. The initial line was placed in the MI region either through a circuit isthmus identified from entrainment mapping or a target identified from pace mapping. A total of 143 VTs (42 stable, 101 unstable) were induced. An isthmus was identified in 25 patients (63%; 5 with only stable VTs, 5 with only unstable VTs, and 15 with both VTs). Inducible VTs were abolished or modified in 100% of patients when the RF line included an isthmus compared with 53% when RF had to be guided by pace mapping (P=0.0002); those with an isthmus identified received shorter ablation lines (4.9+/-2.4 versus 7.4+/-4.3 cm total length, P=0.02). During follow-up, spontaneous VT decreased markedly regardless of whether an isthmus was identified. VT stability and number of morphologies did not influence outcome. CONCLUSIONS: A 4- to 5-cm line of RF lesions abolishes all inducible VTs in more than 50% of patients. Less ablation is required if a reentry circuit isthmus is identified even when multiple and unstable VTs are present.

[Implantable defibrillator. Update]. / Le défibrillateur implantable. Mise au point.

The implantable cardioverter-defibrillator is a device able to detect and efficiently treat life-threatening ventricular arrhythmias. Its decisive accomplishment in reducing sudden cardiac death and total cardiac mortality, opposed to the insufficient reliability of the traditional therapies explains its present ascendancy. In this review, the working principles and the implant techniques are developed, as well as the complications and the usual problems which could be encountered in implanted patients. Finally, the current indications are discussed in the light of recent clinical trials.

Single catheter determination of local electrogram prematurity using simultaneous unipolar and bipolar recordings to replace the surface ECG as a timing reference.

Bipolar recordings eliminate much of the far-field signal, while minimally filtered unipolar recordings contain substantial far-field signal components. These properties may allow the onset of the unipolar recording to serve as a timing reference for the bipolar recording obtained from the same electrode catheter during mapping of focal atrial or ventricular tachycardias. Mapping and RF ablation were performed in 26 patients with focal ventricular tachycardia and 14 patients with focal atrial tachycardia. At 205 mapping sites, simultaneous recordings of (1) minimally filtered unipolar electrograms (0.5-500 Hz), (2) high pass filtered unipolar electrograms (100 Hz), and (3) filtered bipolar recordings (30-500 Hz) were analyzed. The interval between the onset of the minimally filtered unipolar electrogram and the first peak of the bipolar electrogram (UniOn-BiP) correlated closely with the timing of the local electrogram referenced to the surface ECG (r = 0.85, P < 0.001). Of 53 sites where RF ablation was performed, UniOn-BiP was shorter at successful compared to unsuccessful sites (3.8 +/- 3.5 vs 9.2 +/- 5.2 ms, P < 0.001) and was < 15 ms at all successful sites. In conclusion, the comparison of simultaneous unipolar and bipolar electrograms from a single catheter allows assessment of the prematurity of local electrograms from a focal source without the use of the P wave or QRS onset as a timing reference.

Multi atrial maco-re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping.

OBJECTIVES: We sought to characterize re-entry circuits causing intra-atrial re-entrant tachycardias (IARTs) late after the repair of congenital heart disease (CHD) and to define an approach for mapping and ablation, combining anatomy, activation sequence data and entrainment mapping. BACKGROUND: The development of IARTs after repair of CHD is difficult to manage and ablate due to complex anatomy, variable re-entry circuit locations and the frequent co-existence of multiple circuits. METHODS: Forty-seven re-entry circuits were mapped in 20 patients with recurrent IARTs refractory to medical therapy. In the first group (n = 7), ablation was guided by entrainment mapping. In the second group (n = 13), entrainment mapping was combined with a three-dimensional electroanatomic mapping system to precisely localize the scar-related boundaries of re-entry circuits and to reconstruct the activation pattern. RESULTS: Three types of right atrial macro-re-entrant circuits were identified: those related to a lateral right atriotomy scar (19 IARTs), the Eustachian isthmus (18 IARTs) or an atrial septal patch (8 IARTs). Two IARTs originated in the left atrium. Radiofrequency (RF) lesions were applied to transect critical isthmuses in the right atrium. In three patients, the combined mapping approach identified a narrow isthmuses in the lateral atrium, where the first RF lesion interrupted the circuit; the remaining circuits were interrupted by a series of RF lesions across a broader path. Overall, 38 (81%) of 47 IARTs were successfully ablated. During follow-up ranging from 3 to 46 months, 16 (80%) of 20 patients remained free of recurrence. Success was similar in the first 7 (group 1) and last 13 patients (group 2), but fluoroscopy time decreased from 60 +/- 30 to 24 +/- 9 min/procedure, probably related to the increasing experience and ability to monitor catheter position non-fluoroscopically. CONCLUSIONS: Entrainment mapping combined with three-dimensional electroanatomic mapping allows delineation of complex re-entry circuits and critical isthmuses as targets for ablation. Radiofrequency catheter ablation is a reasonable option for treatment of IARTs related to repair of CHD.

Saline-cooled versus standard radiofrequency catheter ablation for infarct-related ventricular tachycardias.

BACKGROUND: Saline cooling of the electrode during radiofrequency (RF) ablation increases lesion size in animal models. If cooled RF also increases lesion size in human infarcts, it should facilitate the termination of ventricular tachycardia (VT). METHODS AND RESULTS: In 66 patients with VT due to prior infarction, 366 ablation sites, which were classified by entrainment and isolated potentials followed by ablation during VT with either standard RF energy (247 sites) or cooled RF (119 sites), were retrospectively reviewed to compare the efficacy for terminating VT. RF energy was applied at 259 isthmus sites, 62 bystander sites, 28 inner loop sites, and 17 outer loop sites. Compared with standard RF, cooled RF terminated VT more frequently at isthmus sites where an isolated potential was present (89% versus 54%, P=0.003), isthmus sites without an isolated potential (36% versus 21%, P=0.04), and at inner loop sites (60% versus 22%, P=0.04). Termination rates were similarly low for cooled and standard RF at bystander sites (14% versus 9%, P=0.56) and outer loop sites (13% versus 11%, P=0.93). CONCLUSIONS: Greater efficacy of cooled RF for terminating VT is consistent with the production of a larger lesion in human infarctions, which should facilitate successful ablation.

The N + 1 difference: a new measure for entrainment mapping.

OBJECTIVES: The purpose of this study was to develop and test a new entrainment mapping measurement, the N + 1 difference. BACKGROUND: Entrainment mapping is useful for identifying re-entry circuit sites but is often limited by difficulty in assessing: 1) changes in QRS complexes or P-waves that indicate fusion, and 2) the postpacing interval (PPI) recorded directly from the stimulation site. METHODS: In computer simulations of re-entry circuits, the interval from a stimulus that reset tachycardia to a timing reference during the second beat after the stimulus was compared with the timing of local activation at the site during tachycardia to define an interval designated the N + 1 difference. The N + 1 difference was compared with the PPI-tachycardia cycle length (TCL) difference in simulations and at 65 sites in 10 consecutive patients with ventricular tachycardia (VT) after myocardial infarction and at 45 sites in 10 consecutive patients with atrial flutter. RESULTS: In simulations, the N + 1 difference was equal to the PPI-TCL difference. During mapping of VT and atrial flutter, the N + 1 difference correlated well with the PPI-TCL difference (r > or = 0.91, p < 0.0001), identifying re-entry circuit sites with sensitivity of > or = 86% and specificity of > or = 90%. Accuracy was similar using either the surface electrocardiogram or an intracardiac electrogram (Eg) as the timing reference. CONCLUSIONS: The N + 1 difference allows entrainment mapping to be used to identify re-entry circuit sites when it is difficult to evaluate Egs at the mapping site or fusion in the surface electrocardiogram.

Diastolic dysfunction precedes myocardial hypertrophy in the development of hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and impaired diastolic function may occur early in systemic hypertension, but longitudinal studies are missing. METHODS: We performed an echocardiographic follow-up study in young initially normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive (ONorm) (n = 17) parents. Blood pressure (BP), LV mass, and mitral inflow were determined at baseline and after 5 years. Pulmonary vein flow pattern assessment and septal myocardial Doppler imaging were additionally performed at follow-up. RESULTS: At follow-up, BP was not significantly different between the two groups (128 +/- 11/84 +/- 10 v 123 +/- 11/81 +/- 5 mm Hg, OHyp v ONorm) but five OHyp had developed mild hypertension. LV mass index remained unchanged and was not different between the two groups at follow-up (92 +/- 17 v 92 +/- 14 g/m2). Diastolic echocardiographic properties were similar at baseline, but, at follow-up, the following differences were found: mitral E deceleration time (209 +/- 32 v 185 +/- 36 msec, P < .05) and pulmonary vein reverse A wave duration (121 +/- 15 v 107 +/- 12 msec, P < .05) were prolonged in the OHyp as compared to the ONorm. Compared to the normotensive subjects, the five OHyp who developed hypertension had more pronounced alterations of LV diastolic function, that is, significantly higher mitral A (54 +/- 7 v 44 +/- 9 cm/sec, hypertensives v normotensives, P < .05), lower E/A ratio (1.31 +/- 0.14 v 1.82 +/- 0.48, P < .05), increased systolic-to-diastolic pulmonary vein flow ratio (1.11 +/- 0.3 v 0.81 +/- 0.16, P < .005), longer myocardial isovolumic relaxation time (57 +/- 7 v 46 +/- 12 msec, P < .05) as well as smaller myocardial E (10 +/- 1 v 13 +/- 2 cm/sec, P < .05) and E/A ratio (1.29 +/- 0.25 v 1.78 +/- 0.43, P < .05), despite similar LV mass (91 +/- 16 v 93 +/- 18 g/m2). CONCLUSIONS: Over a 5-year follow-up, initially lean, normotensive, young men with a moderate genetic risk for hypertension, developed Doppler echocardiographic alterations of LV diastolic function compared to matched offspring of normotensive parents. These alterations were more pronounced in the OHyp who developed mild hypertension and occurred without a distinct rise in LV mass.