Effects of hypobaric hypoxia exposure at high altitude on left ventricular twist in healthy subjects: data from HIGHCARE study on Mount Everest.

AIMS: Previous studies investigating the effect of hypoxia on left ventricle focused on its global function, an approach that may not detect a selective dysfunction of subendocardial layers that are most sensitive to an inadequate oxygen supply. In the HIGHCARE study, aimed at exploring the effects of high altitude hypoxia on multiple biological variables and their modulation by an angiotensin receptor blocker, we addressed the effects of hypobaric hypoxia on both systolic and diastolic left ventricular geometry and function, focusing on echocardiographic assessment of left ventricle twist to indirectly examine subendocardial left ventricular systolic function. METHODS AND RESULTS: In 39 healthy subjects, physiological and echocardiographic variables, including left ventricular twist and a simplified torsion-to-shortening ratio (sTSR), were recorded at sea level, at 3400 m, and at 5400 m altitude (Mount Everest base camp). Both left ventricular twist and sTSR were greater at 5400 m than at sea level (12.6° vs. 9.6° and 0.285 vs. 0.202, P < 0.05 for both), were linearly related to the reduction in arterial oxygen partial pressure (P < 0.01 for both), and were associated with significant changes in LV dimensions and contractility. No effects of angiotensin receptor blockade were observed on these variables throughout the study. CONCLUSION: Our study, for the first time, demonstrates an increase in left ventricular twist at high altitude in healthy subjects exposed to high altitude hypoxia, suggesting the occurrence of subendocardial systolic dysfunction in such condition.

Left-to-right systolic ventricular interaction in patients undergoing biventricular stimulation for dilated cardiomyopathy.

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.

Improvement in left ventricular diastolic stiffness induced by physical training in patients with dilated cardiomyopathy.

BACKGROUND: Diastolic dysfunction in long-term heart failure is accompanied by abnormal neurohormonal control and ventricular stiffness. The diastolic phase is determined by a balance between pressure gradients and intrinsic ventricular wall properties: according to a mathematical model, the latter (ie, left ventricular [LV] elastance, K(LV)) may be calculated by the formula: K(LV) = (70/[DT-20])(2) mm Hg/mL, where DT is the transmitral Doppler deceleration time. METHODS AND RESULTS: In 54 patients with chronic systolic heart failure (39 men, 15 women; age 65 +/- 10 years; New York Heart Association [NYHA], 2.3 +/- 0.9; ejection fraction [EF], 32% +/- 5%), we analyzed the relationship between K(LV) and an index of neurohormonal derangement (levels of brain natriuretic peptide [BNP]), and investigated whether 3 months of physical training could modulate diastolic operating stiffness. Patients were randomized to physical training (n = 27) or to a control group (n = 27). Before and after training, patients underwent Doppler echocardiogram and cardiopulmonary stress test. At baseline, ventricular stiffness was related to BNP levels (P < .01). Training improved NYHA class, exercise performance, and estimated pulmonary pressure. BNP was reduced. Ventricular volumes, mean blood pressure, and EF remained unchanged. A 27% reduction of elastance was observed (K(LV), 0.111 +/- 0.044 from 0.195 +/- 0.089 mm Hg/mL; P < .01), whose magnitude was related to changes in BNP (P < .05) and to K(LV) at baseline (P < .01). No changes in K(LV) were observed in controls after 3 months (0.192 +/- 0.115 from 0.195 +/- 0.121 mm Hg/mL). CONCLUSIONS: In heart failure, left ventricular diastolic stiffness is related to neurohormonal derangement and is modified by physical training. This improvement in LV compliance could result from a combination of hemodynamic improvement and regression of the fibrotic process.

Simultaneous vs. sequential biventricular pacing in dilated cardiomyopathy: an acute hemodynamic study.

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.