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Competing Interests: Conflict of interest: none declared.

Introduction: Cardiac resynchronization therapy (CRT) device implantation guided by an electroanatomic mapping system (EAMS) is an emerging technique that may reduce fluoroscopy and angiography use and provide information on coronary sinus (CS) electrical activation. We evaluated the outcome of the EAMS-guided CRT implantation technique in a multicenter registry., Methods: During the period 2011-2014 we enrolled 125 patients (80% males, age 74 [71-77] years) who underwent CRT implantation by using the EnSite system to create geometric models of the patient's cardiac chambers, build activation mapping of the CS, and guide leads positioning. Two hundred and fifty patients undergoing traditional CRT implantation served as controls. Success and complication rates, fluoroscopy and total procedure times in the overall study population and according to center experience were collected. Centers that performed ≥10 were defined as highly experienced., Results: Left ventricular lead implantation was successful in 122 (98%) cases and 242 (97%) controls (P = 0.76). Median fluoroscopy time was 4.1 (0.3-10.4) minutes in cases versus 16 (11-26) minutes in controls (P < 0.001). Coronary sinus angiography was performed in 33 (26%) cases and 208 (83%) controls (P < 0.001). Complications occurred in 5 (4%) cases and 17 (7%) controls (P = 0.28). Median fluoroscopy time (median 11 minutes vs. 3 minutes, P < 0.001) and CS angiography rate (55% vs. 21%, P < 0.001) were significantly higher in low experienced centers, while success rate and complications rate were similar., Conclusions: EAMS-guided CRT implantation proved safe and effective in both high- and low-experienced centers and allowed to reduce fluoroscopy use by ≈75% and angiography rate by ≈70%., (© 2016 Wiley Periodicals, Inc.)

Left-to-right systolic ventricular interaction (i.e., the phenomenon by which the left ventricle contributes to most of the flow and to two-thirds of the pressure generated by the right ventricle) originates from transmission of systolic forces between the ventricles through the interventricular septum and from the mechanical effect of the common muscle fibers encircling their free walls. As a consequence, any reduction of left ventricular free wall function translates in lower right ventricular pressure or function. We investigated whether systolic ventricular interaction could be evidenced in nine patients with dilated cardiomyopathy in whom a biventricular pacemaker was implanted. Changes in right and left ventricular pressures were measured with high-fidelity catheters, before and after periods of biventricular pacing from the right atrium with different stimulation intervals to the right and left ventricles, respectively. The steady-state changes of left and right ventricular systolic pressure obtained from any single pacing interval combination were considered. We then calculated, with a two-level mixed regression analysis of the entire data set, the relation between changes in left and right systolic pressures: the presence of a statistically significant slope was assumed as evidence of ventricular interaction. The slope of the regression replaced the crude pressure ratio as an estimate of the gain of the interaction; its value compared with values observed in experimental studies. Moreover, its dependence on septal elastance and on right ventricular volume was similar to that already demonstrated for ventricular interaction gain. In conclusion, the linear relationship we found between systolic pressure changes in the two ventricles of patients with dilated cardiomyopathy during biventricular pacing could be explained in terms of ventricular interaction.

Aims: Simultaneous biventricular pacing improves left ventricular (LV) systolic performance in patients with dilated cardiomyopathy and intraventricular conduction delay. We tested the hypothesis that further improvements can be obtained using sequential biventricular pacing by optimizing both atrioventricular and interventricular delays., Methods and Results: In 12 patients, LV pressure, right ventricular (RV) pressure and respective rates of change of pressure (dP/dt) were acutely measured during biventricular pacing with different atrioventricular and interventricular (VVi) intervals ranging from -60 to +40 ms. The average increase vs. baseline in maximum LV dP/dt was higher for sequential than for simultaneous biventricular pacing (VDD mode: 35+/-20 vs. 29+/-18%, P<0.01; DDD mode: 38+/-23 vs. 34+/-25%, P<0.01), with a minority of patients accounting for most of the difference. The mean optimal VVi was -25+/-21 ms in VDD mode and -25+/-26 ms in DDD mode. With these settings, RV dP/dt was not significantly different from baseline. QRS shortening was not predictive of LV dP/dt increase., Conclusion: A significant increase of LV dP/dt with no change in RV dP/dt can be obtained by sequential biventricular pacing as compared to simultaneous biventricular pacing. The highest LV dP/dt is achieved when LV is stimulated before RV. The hemodynamic advantage might be of clinical significance in selected cases.

The aim of this study was to investigate whether, in the short term, physiological blood pressure changes are coupled with changes in urinary sodium excretion in normotensive subjects, maintained at fixed sodium intake and under controlled postural and behavioural conditions. Twelve normotensive subjects were recruited. For each subject, seven urine samples were collected at fixed time intervals during an overall 26 h period: late afternoon (16.00-20.00 hours), evening (20.00-24.00 hours), night (24.00-06.00 hours), quiet wakefulness (06.00-09.00 hours), morning (09.00-12.00 hours), post-prandial (12.00-15.00 hours) and afternoon (15.00-18.00 hours). Blood pressure was monitored by an ambulatory blood pressure device during the whole 26 h period. Each urine sample was used to measure urinary sodium excretion and glomerular filtration rate (creatinine clearance). Blood pressure, heart rate, urinary sodium excretion and glomerular filtration rate recorded in the daytime were higher than those measured during the night-time. A significant positive correlation between mean blood pressure and urinary sodium excretion was found during the night, over the whole 26 h period, and during two subperiods of the daytime: quiet wakefulness and the post-prandial period. The coefficient of the pressure-natriuresis curve was significantly decreased by postural changes. We conclude that, in normotensive subjects, blood pressure and urinary sodium excretion are coupled in the short term. The assumption of an upright posture can mask this relationship, presumably by activating neurohumoral factors.

Introduction: To test the hypothesis that frequent nonsustained ventricular premature beats (VPBs) in patients without underlying heart disease are the first marker of mild systolic dysfunction of the left ventricle, we evaluated whether a subclinical abnormality of left ventricular function and/or an intraventricular conduction defect was present at the first clinical documentation of the arrhythmia., Methods and Results: We compared 57 patients (mean age 46 +/- 14 years) with > 30 VPBs/hour and no heart disease (A) to 32 healthy volunteers (mean age 42 +/- 12 years) without arrhythmia (B). Left ventricular echocardiographic parameters and signal-averaged ECG were evaluated. Filtered QRS duration (98 +/- 10 msec in A vs 98 +/- 7 msec in B) was similar in the two groups. End-diastolic left ventricular diameter (EDLVD) was 50 +/- 6 mm in A versus 47 +/- 3 mm in B (P < 0.005); 15 patients (26%) and none of the controls had EDLVD > or = 55 mm (P < 0.005). Filtered QRS interval was longer in the subgroup of patients (n = 15) with increased EDLVD (> or = 55 mm) compared with the subgroup (n = 42) with EDLVD < 55 mm (106 +/- 9 msec vs 95 +/- 9 msec; P < 0.001) and was related to greater left ventricular mass., Conclusion: We documented a subclinical but significant increase of left ventricular dimensions that suggests that frequent VPBs may be an initial marker of mild systolic dysfunction of the left ventricle. However, an effect of VPBs per se in modifying left ventricular dimensions cannot be excluded.

Purpose: World Health Statistic Annuals between 1973 and 1982 show that mortality from cardiovascular and coronary heart disease fell significantly during this period. Against this background, the present review analyses results from trials of antihypertensive therapy in elderly hypertensives., Study Selection: The review examined available trials specifically devoted to testing the hypothesis that antihypertensive treatment in the elderly hypertensive can lead to a decrease in morbidity and mortality., Results of Data Analysis: Different, randomly allocated, controlled trials have shown that a pharmacological reduction in blood pressure can reduce the incidence of cardiovascular events in the elderly to a similar extent as in young and adult hypertensive patients. Recent reviews have indicated, in contrast to previous suggestions, that the available antihypertensive agents do not have an age-dependent effect. Therefore the choice of antihypertensive therapy is more dependent on previous use or the presence of concomitant diseases., Conclusions: Arterial hypertension is a risk factor in the elderly which can be reduced with pharmacological intervention.

Hypertension becomes more prevalent with advancing age, and the hemodynamic pattern differs from that in younger patients. In the elderly, elevated blood pressure is primarily due to reduced compliance of large vessels, resulting in an increase in total peripheral resistance, but in younger subjects it mainly reflects an increase in cardiac output. Vasodilator drugs, such as calcium antagonists, might therefore be expected to be particularly effective in lowering blood pressure in the elderly. Clinical experience has confirmed the safety and antihypertensive efficacy of these drugs, with some workers suggesting that calcium antagonists are particularly effective in the elderly. A 6-month multicenter study involving 2,184 patients has shown a direct correlation between pretreatment blood pressure and the degree of blood pressure reduction observed during nicardipine treatment with or without other antihypertensive drugs. Isolated systolic hypertension was significantly reduced but diastolic blood pressure was not affected. The incidence of side effects among elderly hypertensive patients, both with and without concomitant disease, was slightly lower than in younger patients.

In 12 mild to moderate hypertensive patients we investigated the acute antihypertensive efficacy of three different doses of nicorandil, a new vasodilating agent which probably acts by increasing the potassium efflux from smooth muscle cells and causing a cellular hyperpolarization. After a 3-day placebo period the patients were given, according to a double-blind Latin-square randomized design, 10, 20 and 30 mg nicorandil as a single acute dose every other day. Blood pressure and the heart rate were measured in both supine and upright positions at various times for 24 h after the dosing; fractional urine collections were obtained at the end of the placebo period and after each active dose. All doses of nicorandil similarly and significantly (P less than 0.01) reduced supine blood pressure, with a peak after 4-6 h (10 mg: -21/-8 mmHg; 20 mg: -20/-9 mmHg; 30 mg: -29/-17 mmHg), and the effect was still present, though reduced, after 24 h; no change in the heart rate was observed. The results from the upright position were similar. There were no significant changes in urine volume and electrolyte excretion during the nicorandil administration. The three different doses of nicorandil caused similar acute blood pressure reductions without change in the heart rate, nor in the urine volume and urinary sodium.

The antihypertensive, humoral, and renal effects of acute single oral administration of placebo and isradipine, a new dihydropyridine calcium antagonist, at doses of 2.5 mg, 5.0 mg, and 7.5 mg once daily were investigated in 11 patients with mild-to-moderate uncomplicated essential hypertension. The patients maintained a constant daily intake of 100 mmol of sodium and 40 mmol of potassium. Placebo and isradipine were randomly administered to each patient, according to a Latin-square design, at intervals of at least 48 hours. The antihypertensive effect was dose-dependent and peaked at two hours after oral administration; changes at the lowest dose were already statistically significant (p less than 0.01). Increases in heart rate were mild and similar with all isradipine doses. Glomerular filtration rate and renal plasma flow showed a trend towards a dose-dependent rise; plasma renin activity was statistically increased (p less than 0.05) following the highest isradipine dose, whereas plasma aldosterone was unmodified. Isradipine resulted in a statistically significant rise (p less than 0.05) in sodium excretion and urine volume, which was similar with all active doses. In conclusion, the antihypertensive efficacy of isradipine is dose-dependent, whereas the natriuretic and diuretic effects are already at maximum following 2.5 mg per day, the lowest dose in this study.