Vincent Juvé
email: vincent.juve@univ-lemans.fr

Gwenaëlle Vaudel

Zoltan Ollmann

Janos Hebling

Vasily Temnov

Vitalyi Gusev

Thomas Pezeril

Ultrafast tunable modulation of light polarization at terahertz frequencies

December 4, 2018

Controlling light polarization is one of the most essential routines in modern optical technology. Since the demonstration of optical pulse shaping by spatial light modulators and its potential in controlling the quantum reaction pathways, it paved the way for many applications as a coherent control of the photoionization process or as polarization shaping of terahertz (THz) pulses. Here, we evidenced efficient nonresonant and noncollinear χ (2) -type light-matter interaction in femtosecond polarization-sensitive time-resolved optical measurements. Such nonlinear optical interaction of visible light and ultrashort THz pulses leads to THz modulation of visible light polarization in bulk LiNbO 3 crystal. Theoretical simulations based on the wave propagation equation capture the physical processes underlying this nonlinear effect. Apart from the observed tunable polarization modulation of visible pulses at ultrahigh frequencies, this physical phenomenon can be envisaged in THz depthprofiling of materials.

Over the last decade, ultrafast terahertz (THz) spectroscopy has gained tremendous attention thanks to the development of high power ultrafast laser systems [START_REF] Kampfrath | Resonant and nonresonant control over matter and light by intense terahertz transients[END_REF], which allowed the generation of intense single-cycle picosecond pulses of electric field at THz frequencies [START_REF] Yeh | Generation of 10 µ j ultrashort terahertz pulses by optical rectification[END_REF][START_REF] Hirori | Single-cycle terahertz pulses with amplitudes exceeding 1 mv/cm generated by optical rectification in linbo 3[END_REF]. Their relatively long optical cycle period (1 ps for 1 THz) and high electric field (from hundreds of kV/cm to a few MV/cm) provide a new tool for studying fundamental aspects of lightmatter interactions like THz-driven ballistic charge currents in semiconductors [START_REF] Kuehn | Coherent ballistic motion of electrons in a periodic potential[END_REF][START_REF] Schubert | Sub-cycle control of terahertz high-harmonic generation by dynamical bloch oscillations[END_REF], linear [START_REF] Kampfrath | Coherent terahertz control of antiferromagnetic spin waves[END_REF] and nonlinear [START_REF] Baierl | Nonlinear spin control by terahertz-driven anisotropy fields[END_REF] control of antiferromagnetic spin waves, THz-induced dynamics in metallic ferromagnets [START_REF] Vicario | Off-resonant magnetization dynamics phase-locked to an intense phase-stable terahertz transient[END_REF] and transparent magneto-optical media [START_REF] Subkhangulov | Terahertz modulation of the faraday rotation by laser pulses via the optical kerr effect[END_REF], or even an ultrafast switching of electric polarization in ferroelectrics [START_REF] Mankowsky | Ultrafast reversal of the ferroelectric polarization[END_REF]. Field-resolved detection of ultrashort THz pulses has been well known for many years, and the most common technique is based on free-space electrooptic sampling, which can be implemented in two ways: non phase-matched electro-optic sampling in crystals like ZnTe [START_REF] Planken | Measurement and calculation of the orientation dependence of terahertz pulse detection in znte[END_REF] or GaP [START_REF] Wu | 7 terahertz broadband gap electro-optic sensor[END_REF] and phase-matched electro-optic sampling in a GaSe crystal [START_REF] Kübler | Ultrabroadband detection of multi-terahertz field transients with gase electro-optic sensors: Approaching the near infrared[END_REF][START_REF] Liu | Gase crystals for broadband terahertz wave detection[END_REF]. The latter relies on phasematched propagation of THz and visible pulses in a crystal leading to an efficient ordinary-to-extraordinary conversion for visible photons at approximately the same frequency, hω e = hω o ± hω THz o hω o . This leads to the polarization change of an optical pulse, which is detected by the polarization-sensitive scheme, and to the field resolved detection of a THz pulse. Since nonresonant THz induced optical nonlinearities in dielectric crystals are nearly instantaneous, the magnitude of the polarization change should be determined solely by the spatiotemporal dynamics of interacting THz and visible pulses propagating inside the crystal. Consequently, the polarization switching time lies in the picosecond range governed by the duration of the pulses involved. In other words, such nonresonant nonlinear optical interactions set the fundamental speed limits of electro-optical modulation, which is limited to nanosecond switching time for conventional electro-optic devices [START_REF] Lu | Wide-bandwidth high-frequency electro-optic modulator based on periodically poled linbo 3[END_REF]. Although phase-matched electro-optics seems to be appealing to achieve ultrafast control over the polarization state of light, to the best of our knowledge, it has been only applied to detect and characterize THz fields. Moreover, the relatively low efficiency and the third-order optical nonlinearity in a GaSe crystal are limiting its impact [START_REF] Sell | Phase-locked generation and field-resolved detection of widely tunable terahertz pulses with amplitudes exceeding 100 mv/cm[END_REF].

Here we report on the efficient modulation of light's polarization by THz ultrashort pulses via the second-order nonlinear optical interaction inside a LiNbO 3 crystal, where an intense THz pump and a visible probe pulse interact during their propagation inside the crystal of thickness 1 mm. Optical properties of visible probe pulses are monitored by polarization sensitive measurements (rotation and ellipticity) as a function of the pump-probe delay time. Two dis- ). Due to the polarization-sensitive detection scheme with a half waveplate, the measured signal is linked to the rotation of the polarization state of the visible probe pulses induced by nonlinear optical interaction with the THz pulses propagating in the crystal and exhibits time domain oscillations at two distinct frequencies of 0.22 THz (low frequency ν -) and 0.69 THz (high-frequency ν + ), respectively. For this particular experimental configuration, the rotation angle, denoted as the polarization rotation angle ∆θ, is ap-proximately 1 • , which corresponds to a polarization conversion efficiency of ∼ 5%. A similar transient shape is observed when measuring the ellipticity change with a quarter-wave plate (not shown). Moreover, the signals are of comparable amplitude when measuring the rotation or ellipticity changes, but they are phase-shifted by roughly π/2, which means that the rotation is maximum when the ellipticity is 0 and vice versa. The occurrence of high-frequency ν + and low-frequency ν -can be uniquely attributed to copropagating and counterpropagating THz and visible pulses, respectively. The frequency changes from high to low, and vice versa, each time the THz pulse is reflected at one of the crystal surfaces. with n gr o ∼ 3.06 the index of light polarized along the ordinary and n gr THz = n THz the refractive index of the THz pulse, considering that the LiNbO 3 is not dispersive in this frequency range. The different time intervals ∆τ +,-are experimentally found to be 12.1 ps and 32.3 ps, and, considering the value of the visible group refractive index, one can extract the THz ordinary refractive index n THz ≈ 6.75, which is in good agreement with the literature [START_REF] Schall | Far infrared properties of electro-optic crystals measured by thz timedomain spectroscopy[END_REF][START_REF] Unferdorben | Measurement of refractive index and absorption coefficient of congruent and stoichiometric lithium niobate in the terahertz range[END_REF]. Finally the signal duration of hundreds of picoseconds and the drops in amplitude for each reflection at the interfaces are explained by the absorption coefficient of the LiNbO 3 in the THz spectral range and by the THz reflection coefficient, which is roughly 75% for the field amplitude.

Measurements at different probe angles α in ranging from 0 to 16 • have been performed and are displayed in Fig. 1 (c) for a probe's wavelength λ o = 400 nm. The curve at 0 • reflects interfacial effect as described below. On top of this effect, noncollinear geometry gives birth to the single low and high frequencies, which increase continuously as a function of the angle α in . Systematic investigation of the evolution of the observed frequencies versus the probe angles α in and for two wavelengths λ o = 400 nm and λ o = 800 nm was carried out and is displayed in Fig. 2 (a). For each wavelength, two frequency branches (ν + and ν -) appear, which correspond to co-and counter-propagating THz and visible pulses as described previously. The maximum measured frequency is 1.6 THz (α in ≈ 15 • ) for λ o = 400 nm and 1.1 THz (α in ≈ 22 • ) for λ o = 800 nm. Dashed lines correspond to the results of the theoretical solution based on our model, which is summarized by Eq. ( 2), and are perfectly in agreement with experimental results. Fig. 2 (b) demonstrates perfect agreement between the experimental and simulated polarization rotation in time domain.

For a quantitative insight into the nonlinear process involved here, we have measured the amplitude of the change of the light's polarization angle ∆θ while sweeping the internal angle α in for a wavelength of 400 nm. In Fig. 3, ∆θ of the first occurring oscillations (ν + or ν -) is plotted as a function of the frequencies for the two experimental configurations namely the front-side and back-side probing Data ν +, _ for 400 nm Data ν +, _ for 800 nm Simulations for 400 nm Simulations for 800 nm geometries. The first striking feature is the measured maximum polarization rotation angle, occurring at 0.6 THz for ν + , which is as high as 6 • . This corresponds to a light polarization conversion efficiency of 20% upon the presence of the THz pulse. This light's polarization rotation angle is the largest, for the considered THz field amplitude, reported so far in the literature (in the order of 1 degree in ultrafast experiments [START_REF] Vicario | Off-resonant magnetization dynamics phase-locked to an intense phase-stable terahertz transient[END_REF][START_REF] Mikhaylovskiy | Colossal magneto-optical modulation at terahertz frequencies by counterpropagating femtosecond laser pulses in tb 3 ga 5 o 1 2[END_REF]). Furthermore, unlike GaSe [START_REF] Sell | Phase-locked generation and field-resolved detection of widely tunable terahertz pulses with amplitudes exceeding 100 mv/cm[END_REF], no saturation effect is evidenced (see the inset of Fig. 3), opening the way to improving conversion efficiency. The second striking feature is the difference in the maximum rotation angle for ν + and ν -with a almost 3 times higher amplitude for ν + .

Along with the experimental data points, the results of numerical evaluation of the analytical theoretical prediction of time integration of Eq. ( 2) are plotted for both co-(ν + ) and counter-propagating (ν -) pulses. These are in a good agreement with the experimental results. Moreover, the spectral amplitude of the polarization rotation transients is proportional to the spectral components of the THz pulse used in the experiments shown in the dashed line in Fig. 3. In light of these results, the main effect of tuning the angle is to fulfill the phase-matching condition for different frequency components contained in the pump THz spectrum, which directly leads to the THz pulse sampling in the frequency domain and, thus, allows to adjust the modulation frequency of the probe pulse. The experimental results were analysed by theoretical simulations of the scattering process between the light and THz pulses within the sample. We considered second-order nonlinear interaction between the electric field of the ordinary polarized THz pulse and of the ordinary polarized visible probe, leading to the generation of an extraordinary optical beam. Solving the wave propagation equation for the extraordinary beam generated by this interaction leads to the expression for the signal amplitude as the function of the time delay τ between the THz pump and the optical probe beam, which is governed by an interplay between distinct phase-and group-matching conditions for visible and THz electromagnetic fields. For the half-wave plate and Wollaston prism arrangement, the theoretical modelling gives nal S(τ, α in ) ∼ +∞ -∞ I ± λ/2 (t, τ, α in )dt is the time integral of Eq. ( 2) and leads to the time evolution of the polarization state (rotation and ellipticity) of the probe beam. The simulated transient (see figure 2 (b)) gives information about the modulation frequency and the amplitude as a function of the angle α in . Multiple reflections can also be simulated. In our model, we only consider the second-order nonlinear effect occurring in the bulk of the crystal. In the simulations, there are no free parameters: the model requires only the parameters of the material and of the pulse, which are determined independently. The simulated transients are in excellent agreement with the experimental ones as we included the reflection coefficient as well as the THz absorption of the crystal (see Fig. 2 (b)). The computed frequencies of the oscillations versus the angle α in are displayed in dashed lines in Fig. 2 and perfectly agree the experimental observation for two different wavelengths. There is as well a good agreement between the calculated and measured amplitudes of the oscillations, which are displayed in Fig. 3 with only a scaling factor. It is interesting to note that the ratio of the ν + and ν -simulated amplitudes is frequency independent and is equal to 2.7. This ratio can be explained by the longer interaction time of the THz pulse with the copropagating light field than with the counter-propagating one, We now discuss the physical effect underlying the THz controlled polarization rotation of the visible probe pulse. In conventional non phase-matched free-space electro-optic sampling, in ZnTe crystal for instance, the THz and optical gate pulses are group-matched. Thus, the optical probe pulse accumulates a phase shift at a constant rate during the propagation in the crystal proportional to the THz electric field value set by the relative time delay between the pulses. This technique has been widely used for decades in linear and nonlinear THz spectroscopy [START_REF] Grischkowsky | Far-infrared time-domain spectroscopy with terahertz beams of dielectrics and semiconductors[END_REF] and provides a sampling of the THz pulse in time domain by the light pulse. Moreover, the effect exists both for collinear [START_REF] Van Exter | High-brightness terahertz beams characterized with an ultrafast detector[END_REF][START_REF] Wu | Free-space electro-optic sampling of terahertz beams[END_REF] and noncollinear [START_REF] Shan | Single-shot measurement of terahertz electromagnetic pulses by use of electro-optic sampling[END_REF] propagation of THz and light pulses. In the case of LiNbO 3 , the optical and THz group indices are mismatched by roughly a factor of 2, which leads to a different interpretation of our experimental results. The observed experimental signals have two origins: from the interface region and from the bulk. The effect of the interface region can be clearly seen in Fig. 1 (c) for α in = 0 • at τ = 0, 32 and 47 ps corresponding to the injection or reflection of THz pulses from the surface as seen by the optical probe. Consequently, the non-zero polarization rotation will be proportional to τ -∞ E THz (t)dt = 0. Once the THz pulse is completely inside the crystal, the polarization rotation accumulated by the optical pulse will be proportional to the integral of the THz pulse +∞ -∞ E THz (t)dt = 0 and, thus, leads to no detectable signal. It has to be noted that the observed "interfacial" effect exploits the substan-tial group mismatch between the optical and THz pulses (common for most materials) and can be used to retrieve the temporal THz pulse shape. The periodic oscillation of the signal relies on the complex interplay between phase and group-matching conditions (see Eq. ( 2)) due to optical second order nonlinear effect occurring inside the sample and is observed only for noncollinear propagation of the THz and light pulses. Its frequency can be adjusted by tuning the angle between the two incident beams. The angular dependence of the oscillation amplitude makes possible to retrieve the THz spectrum as shown in Fig. 3.

I ± λ/2 (t, τ, α in ) ∼ πd 22 n e n 2 o 2λ o × A o (t -τ -Ln gr o /c) L 0 dzE THz t -(n THz ∓ n gr e ) z c × A o t -τ -(n gr o -n gr e ) z c sin 2π λ o (n e -n o )z + Φ(α in ) , (2)
One potential application would be to use picosecond pulses of visible light with a pulse duration roughly equal to ∆τ -or ∆τ + . This configuration would lead to an ultrafast periodic modulation of the polarization state of the visible light at THz frequency, depending on the crossing angle α in between THz and optical pulses. As the modulation frequency can be modified easily it can be tuned to resonantly drive systems like coherent THz optical phonon excitation in solids [START_REF] Sokolowski-Tinten | Femtosecond x-ray measurement of coherent lattice vibrations near the lindemann stability limit[END_REF][START_REF] Fritz | Ultrafast bond softening in bismuth: Mapping a solid's interatomic potential with xrays[END_REF] and Raman-active media [START_REF] Misawa | Applications of polarization-shaped femtosecond laser pulses[END_REF] for example. Another possible application of our experimental scheme is to add the third (axial) coordinate to the well-known "2D imaging with THz waves" [START_REF] Hu | Imaging with terahertz waves[END_REF][START_REF] Wu | Two-dimensional electro-optic imaging of thz beams[END_REF][START_REF] Nuss | Chemistry is right for t-ray imaging[END_REF][START_REF] Fitzgerald | An introduction to medical imaging with coherent terahertz frequency radiation[END_REF], which currently provides only lateral resolution. The micrometer axial resolution for depth-profiling of the suggested three-dimensional imaging technique is controlled by the spatial overlap of the THz and probe light pulses and, in case of their counter-propagation, could outperform the "echography with THz pulses" [START_REF] Jackson | Terahertz pulse imaging in archaeology[END_REF].

In conclusion, we have experimentally demonstrated an ultrafast tunable polarization modulation of optical pulses at a wavelength of 400 and 800 nm caused by nonresonant interaction with an ultrashort THz pulse in LiNbO 3 crystal. The maximum polarization rotation and ellipticity was measured to be ∼ 6% and ∼ 8% at the internal angle of ∼ 8.5 • between the THz pulse and a 400 nm visible probe. This effect is modelled by solving the wave propagation equation, and analytical expressions show that an interplay between distinct phase-and group-matching conditions for visible and THz electromagnetic fields determines the overall conversion efficiency. Being in excellent agreement with theoretical calculations, our experimental findings pave the way to the design of ultrafast and efficient miniaturized electrooptical devices for pulse shaping operating in the multi-THz range.

Funding

Campus France; Rgion Pays de la Loire (NNN-Telecom, Ultrasfast Acoustics in Hybrid Magnetic Nanostructures and Echopico projects).

Figure 1 :

 1 Figure 1: (a) Schematic of the time-resolved polarization change measurement in a z-cut LiNbO 3 crystal in the frontside probing configuration. HWP, half-wave plate; QWP, quarter-wave plate. WP, Wollaston prism. BPD, balanced photodiodes. LIA, lock-in amplifier. L, samples thickness. (b) Relative change of the probe light polarization orientation as a function of the time delay between the THz pump pulse and the 400 nm probe pulse for α out = 25 • (α in = 10 • ) the back-side probing configuration, shown by the small sketch. (c) Ultrafast transients obtained for different probe angles as a function of the time delay between the pump and the probe in the back-side probing configuration. The curves are normalized and shifted for the sake of clarity.

  The alternating time windows for the observation of copropagating and counterpropagating THz and visible pulses inside the crystal of thickness L= 1 mm (see Fig 1 (b)) are governed by group velocities, ∆τ + ≈ L c (n THz -n gr o ) and ∆τ -≈ L c (n THz + n gr o ) , (1)

Figure 2 :

 2 Figure 2: (a) Measured frequencies as a function of the probes incidence angle. Two different probing wavelengths (triangles) are plotted as well as the predictions of our model for both wavelengths (dashed lines). (b) Comparison of the experimental and simulated polarization rotation transients for an angle α in = 10 • and λ o = 400 nm. The corresponding oscillations frequencies are ν + = 0.69 THz and ν -= 0.27 THz. Vertical dotted lines separate the regions with co-and counter-propagating pump and probe pulses.

where d 22 Figure 3 :

 223 Figure 3: Polarization rotation angle as a function of the measured frequency for the high-and low-frequency modes. For comparison, the experimental THz spectrum is shown in the dashed line. Inset, polarization rotation angle for the high-frequency oscillation versus the THz electric field strength for α in = 9.3 • and λ o = 400 nm in the front-side configuration.

= 2 . 7 ,

 27 agreeing with the experimental value of ≈ 3. Deviation of the numerical simulation starting at around 0.4 THz for the back-side configuration, corresponding to an angle α in ≈ 15 • (α out ≈ 38 • ), can be explained by the geometrical effect of the beams crossing in the sample which is neglected in our model.


Vincent Juvé
email: vincent.juve@univ-lemans.fr

Gwenaëlle Vaudel

Zoltan Ollmann

Janos Hebling

Vasily Temnov

Vitalyi Gusev

Thomas Pezeril

Ultrafast tunable modulation of light polarization at terahertz frequencies

December 4, 2018

Controlling light polarization is one of the most essential routines in modern optical technology. Since the demonstration of optical pulse shaping by spatial light modulators and its potential in controlling the quantum reaction pathways, it paved the way for many applications as a coherent control of the photoionization process or as polarization shaping of terahertz (THz) pulses. Here, we evidenced efficient nonresonant and noncollinear χ (2) -type light-matter interaction in femtosecond polarization-sensitive time-resolved optical measurements. Such nonlinear optical interaction of visible light and ultrashort THz pulses leads to THz modulation of visible light polarization in bulk LiNbO 3 crystal. Theoretical simulations based on the wave propagation equation capture the physical processes underlying this nonlinear effect. Apart from the observed tunable polarization modulation of visible pulses at ultrahigh frequencies, this physical phenomenon can be envisaged in THz depthprofiling of materials.

Over the last decade, ultrafast terahertz (THz) spectroscopy has gained tremendous attention thanks to the development of high power ultrafast laser systems [START_REF] Kampfrath | Resonant and nonresonant control over matter and light by intense terahertz transients[END_REF], which allowed the generation of intense single-cycle picosecond pulses of electric field at THz frequencies [START_REF] Yeh | Generation of 10 µ j ultrashort terahertz pulses by optical rectification[END_REF][START_REF] Hirori | Single-cycle terahertz pulses with amplitudes exceeding 1 mv/cm generated by optical rectification in linbo 3[END_REF]. Their relatively long optical cycle period (1 ps for 1 THz) and high electric field (from hundreds of kV/cm to a few MV/cm) provide a new tool for studying fundamental aspects of lightmatter interactions like THz-driven ballistic charge currents in semiconductors [START_REF] Kuehn | Coherent ballistic motion of electrons in a periodic potential[END_REF][START_REF] Schubert | Sub-cycle control of terahertz high-harmonic generation by dynamical bloch oscillations[END_REF], linear [START_REF] Kampfrath | Coherent terahertz control of antiferromagnetic spin waves[END_REF] and nonlinear [START_REF] Baierl | Nonlinear spin control by terahertz-driven anisotropy fields[END_REF] control of antiferromagnetic spin waves, THz-induced dynamics in metallic ferromagnets [START_REF] Vicario | Off-resonant magnetization dynamics phase-locked to an intense phase-stable terahertz transient[END_REF] and transparent magneto-optical media [START_REF] Subkhangulov | Terahertz modulation of the faraday rotation by laser pulses via the optical kerr effect[END_REF], or even an ultrafast switching of electric polarization in ferroelectrics [START_REF] Mankowsky | Ultrafast reversal of the ferroelectric polarization[END_REF]. Field-resolved detection of ultrashort THz pulses has been well known for many years, and the most common technique is based on free-space electrooptic sampling, which can be implemented in two ways: non phase-matched electro-optic sampling in crystals like ZnTe [START_REF] Planken | Measurement and calculation of the orientation dependence of terahertz pulse detection in znte[END_REF] or GaP [START_REF] Wu | 7 terahertz broadband gap electro-optic sensor[END_REF] and phase-matched electro-optic sampling in a GaSe crystal [START_REF] Kübler | Ultrabroadband detection of multi-terahertz field transients with gase electro-optic sensors: Approaching the near infrared[END_REF][START_REF] Liu | Gase crystals for broadband terahertz wave detection[END_REF]. The latter relies on phasematched propagation of THz and visible pulses in a crystal leading to an efficient ordinary-to-extraordinary conversion for visible photons at approximately the same frequency, hω e = hω o ± hω THz o hω o . This leads to the polarization change of an optical pulse, which is detected by the polarization-sensitive scheme, and to the field resolved detection of a THz pulse. Since nonresonant THz induced optical nonlinearities in dielectric crystals are nearly instantaneous, the magnitude of the polarization change should be determined solely by the spatiotemporal dynamics of interacting THz and visible pulses propagating inside the crystal. Consequently, the polarization switching time lies in the picosecond range governed by the duration of the pulses involved. In other words, such nonresonant nonlinear optical interactions set the fundamental speed limits of electro-optical modulation, which is limited to nanosecond switching time for conventional electro-optic devices [START_REF] Lu | Wide-bandwidth high-frequency electro-optic modulator based on periodically poled linbo 3[END_REF]. Although phase-matched electro-optics seems to be appealing to achieve ultrafast control over the polarization state of light, to the best of our knowledge, it has been only applied to detect and characterize THz fields. Moreover, the relatively low efficiency and the third-order optical nonlinearity in a GaSe crystal are limiting its impact [START_REF] Sell | Phase-locked generation and field-resolved detection of widely tunable terahertz pulses with amplitudes exceeding 100 mv/cm[END_REF].

Here we report on the efficient modulation of light's polarization by THz ultrashort pulses via the second-order nonlinear optical interaction inside a LiNbO 3 crystal, where an intense THz pump and a visible probe pulse interact during their propagation inside the crystal of thickness 1 mm. Optical properties of visible probe pulses are monitored by polarization sensitive measurements (rotation and ellipticity) as a function of the pump-probe delay time. Two dis- ). Due to the polarization-sensitive detection scheme with a half waveplate, the measured signal is linked to the rotation of the polarization state of the visible probe pulses induced by nonlinear optical interaction with the THz pulses propagating in the crystal and exhibits time domain oscillations at two distinct frequencies of 0.22 THz (low frequency ν -) and 0.69 THz (high-frequency ν + ), respectively. For this particular experimental configuration, the rotation angle, denoted as the polarization rotation angle ∆θ, is ap-proximately 1 • , which corresponds to a polarization conversion efficiency of ∼ 5%. A similar transient shape is observed when measuring the ellipticity change with a quarter-wave plate (not shown). Moreover, the signals are of comparable amplitude when measuring the rotation or ellipticity changes, but they are phase-shifted by roughly π/2, which means that the rotation is maximum when the ellipticity is 0 and vice versa. The occurrence of high-frequency ν + and low-frequency ν -can be uniquely attributed to copropagating and counterpropagating THz and visible pulses, respectively. The frequency changes from high to low, and vice versa, each time the THz pulse is reflected at one of the crystal surfaces. with n gr o ∼ 3.06 the index of light polarized along the ordinary and n gr THz = n THz the refractive index of the THz pulse, considering that the LiNbO 3 is not dispersive in this frequency range. The different time intervals ∆τ +,-are experimentally found to be 12.1 ps and 32.3 ps, and, considering the value of the visible group refractive index, one can extract the THz ordinary refractive index n THz ≈ 6.75, which is in good agreement with the literature [START_REF] Schall | Far infrared properties of electro-optic crystals measured by thz timedomain spectroscopy[END_REF][START_REF] Unferdorben | Measurement of refractive index and absorption coefficient of congruent and stoichiometric lithium niobate in the terahertz range[END_REF]. Finally the signal duration of hundreds of picoseconds and the drops in amplitude for each reflection at the interfaces are explained by the absorption coefficient of the LiNbO 3 in the THz spectral range and by the THz reflection coefficient, which is roughly 75% for the field amplitude.

Measurements at different probe angles α in ranging from 0 to 16 • have been performed and are displayed in Fig. 1 (c) for a probe's wavelength λ o = 400 nm. The curve at 0 • reflects interfacial effect as described below. On top of this effect, noncollinear geometry gives birth to the single low and high frequencies, which increase continuously as a function of the angle α in . Systematic investigation of the evolution of the observed frequencies versus the probe angles α in and for two wavelengths λ o = 400 nm and λ o = 800 nm was carried out and is displayed in Fig. 2 (a). For each wavelength, two frequency branches (ν + and ν -) appear, which correspond to co-and counter-propagating THz and visible pulses as described previously. The maximum measured frequency is 1.6 THz (α in ≈ 15 • ) for λ o = 400 nm and 1.1 THz (α in ≈ 22 • ) for λ o = 800 nm. Dashed lines correspond to the results of the theoretical solution based on our model, which is summarized by Eq. ( 2), and are perfectly in agreement with experimental results. Fig. 2 (b) demonstrates perfect agreement between the experimental and simulated polarization rotation in time domain.

For a quantitative insight into the nonlinear process involved here, we have measured the amplitude of the change of the light's polarization angle ∆θ while sweeping the internal angle α in for a wavelength of 400 nm. In Fig. 3, ∆θ of the first occurring oscillations (ν + or ν -) is plotted as a function of the frequencies for the two experimental configurations namely the front-side and back-side probing Data ν +, _ for 400 nm Data ν +, _ for 800 nm Simulations for 400 nm Simulations for 800 nm geometries. The first striking feature is the measured maximum polarization rotation angle, occurring at 0.6 THz for ν + , which is as high as 6 • . This corresponds to a light polarization conversion efficiency of 20% upon the presence of the THz pulse. This light's polarization rotation angle is the largest, for the considered THz field amplitude, reported so far in the literature (in the order of 1 degree in ultrafast experiments [START_REF] Vicario | Off-resonant magnetization dynamics phase-locked to an intense phase-stable terahertz transient[END_REF][START_REF] Mikhaylovskiy | Colossal magneto-optical modulation at terahertz frequencies by counterpropagating femtosecond laser pulses in tb 3 ga 5 o 1 2[END_REF]). Furthermore, unlike GaSe [START_REF] Sell | Phase-locked generation and field-resolved detection of widely tunable terahertz pulses with amplitudes exceeding 100 mv/cm[END_REF], no saturation effect is evidenced (see the inset of Fig. 3), opening the way to improving conversion efficiency. The second striking feature is the difference in the maximum rotation angle for ν + and ν -with a almost 3 times higher amplitude for ν + . Along with the experimental data points, the results of numerical evaluation of the analytical theoretical prediction of time integration of Eq. ( 2) are plotted for both co-(ν + ) and counter-propagating (ν -) pulses. These are in a good agreement with the experimental results. Moreover, the spectral amplitude of the polarization rotation transients is proportional to the spectral components of the THz pulse used in the experiments shown in the dashed line in Fig. 3. In light of these results, the main effect of tuning the angle is to fulfill the phase-matching condition for different frequency components contained in the pump THz spectrum, which directly leads to the THz pulse sampling in the frequency domain and, thus, allows to adjust the modulation frequency of the probe pulse.

The experimental results were analysed by theoretical simulations of the scattering process between the light and THz pulses within the sample. We considered second-order nonlinear interaction between the electric field of the ordinary polarized THz pulse and of the ordinary polarized visible probe, leading to the generation of an extraordinary optical beam. Solving the wave propagation equation for the extraordinary beam generated by this interaction leads to the expression for the signal amplitude as the function of the time delay τ between the THz pump and the optical probe beam, which is governed by an interplay between distinct phase-and group-matching conditions for visible and THz electromagnetic fields. For the half-wave plate and Wollaston prism arrangement, the theoretical modelling gives nal S(τ, α in ) ∼ +∞ -∞ I ± λ/2 (t, τ, α in )dt is the time integral of Eq. ( 2) and leads to the time evolution of the polarization state (rotation and ellipticity) of the probe beam. The simulated transient (see figure 2 (b)) gives information about the modulation frequency and the amplitude as a function of the angle α in . Multiple reflections can also be simulated. In our model, we only consider the second-order nonlinear effect occurring in the bulk of the crystal. In the simulations, there are no free parameters: the model requires only the parameters of the material and of the pulse, which are determined independently. The simulated transients are in excellent agreement with the experimental ones as we included the reflection coefficient as well as the THz absorption of the crystal (see Fig. 2 (b)). The computed frequencies of the oscillations versus the angle α in are displayed in dashed lines in Fig. 2 and perfectly agree the experimental observation for two different wavelengths. There is as well a good agreement between the calculated and measured amplitudes of the oscillations, which are displayed in Fig. 3 with only a scaling factor. It is interesting to note that the ratio of the ν + and ν -simulated amplitudes is frequency independent and is equal to 2.7. This ratio can be explained by the longer interaction time of the THz pulse with the copropagating light field than with the counter-propagating one, We now discuss the physical effect underlying the THz controlled polarization rotation of the visible probe pulse. In conventional non phase-matched free-space electro-optic sampling, in ZnTe crystal for instance, the THz and optical gate pulses are group-matched. Thus, the optical probe pulse accumulates a phase shift at a constant rate during the propagation in the crystal proportional to the THz electric field value set by the relative time delay between the pulses. This technique has been widely used for decades in linear and nonlinear THz spectroscopy [START_REF] Grischkowsky | Far-infrared time-domain spectroscopy with terahertz beams of dielectrics and semiconductors[END_REF] and provides a sampling of the THz pulse in time domain by the light pulse. Moreover, the effect exists both for collinear [START_REF] Van Exter | High-brightness terahertz beams characterized with an ultrafast detector[END_REF][START_REF] Wu | Free-space electro-optic sampling of terahertz beams[END_REF] and noncollinear [START_REF] Shan | Single-shot measurement of terahertz electromagnetic pulses by use of electro-optic sampling[END_REF] propagation of THz and light In the case of LiNbO 3 , the optical and THz group indices are mismatched by roughly a factor of 2, which leads to a different interpretation of our experimental results. The observed experimental signals have two origins: from the interface region and from the bulk. The effect of the interface region can be clearly seen in Fig. 1 (c) for α in = 0 • at τ = 0, 32 and 47 ps corresponding to the injection or reflection of THz pulses from the surface as seen by the optical probe. Consequently, the non-zero polarization rotation will be proportional to τ -∞ E THz (t)dt = 0. Once the THz pulse is completely inside the crystal, the polarization rotation accumulated by the optical pulse will be proportional to the integral of the THz pulse +∞ -∞ E THz (t)dt = 0 and, thus, leads to no detectable signal. It has to be noted that the observed "interfacial" effect exploits the substan-tial group mismatch between the optical and THz pulses (common for most materials) and can be used to retrieve the temporal THz pulse shape. The periodic oscillation of the signal relies on the complex interplay between phase and group-matching conditions (see Eq. ( 2)) due to optical second order nonlinear effect occurring inside the sample and is observed only for noncollinear propagation of the THz and light pulses. Its frequency can be adjusted by tuning the angle between the two incident beams. The angular dependence of the oscillation amplitude makes possible to retrieve the THz spectrum as shown in Fig. 3.

I ± λ/2 (t, τ, α in ) ∼ πd 22 n e n 2 o 2λ o × A o (t -τ -Ln gr o /c) L 0 dzE THz t -(n THz ∓ n gr e ) z c × A o t -τ -(n gr o -n gr e ) z c sin 2π λ o (n e -n o )z + Φ(α in ) , (2)
One potential application would be to use picosecond pulses of visible light with a pulse duration roughly equal to ∆τ -or ∆τ + . This configuration would lead to an ultrafast periodic modulation of the polarization state of the visible light at THz frequency, depending on the crossing angle α in between THz and optical pulses. As the modulation frequency can be modified easily it can be tuned to resonantly drive systems like coherent THz optical phonon excitation in solids [START_REF] Sokolowski-Tinten | Femtosecond x-ray measurement of coherent lattice vibrations near the lindemann stability limit[END_REF][START_REF] Fritz | Ultrafast bond softening in bismuth: Mapping a solid's interatomic potential with xrays[END_REF] and Raman-active media [START_REF] Misawa | Applications of polarization-shaped femtosecond laser pulses[END_REF] for example. Another possible application of our experimental scheme is to add the third (axial) coordinate to the well-known "2D imaging with THz waves" [START_REF] Hu | Imaging with terahertz waves[END_REF][START_REF] Wu | Two-dimensional electro-optic imaging of thz beams[END_REF][START_REF] Nuss | Chemistry is right for t-ray imaging[END_REF][START_REF] Fitzgerald | An introduction to medical imaging with coherent terahertz frequency radiation[END_REF], which currently provides only lateral resolution. The micrometer axial resolution for depth-profiling of the suggested three-dimensional imaging technique is controlled by the spatial overlap of the THz and probe light pulses and, in case of their counter-propagation, could outperform the "echography with THz pulses" [START_REF] Jackson | Terahertz pulse imaging in archaeology[END_REF].

In conclusion, we have experimentally demonstrated an ultrafast tunable polarization modulation of optical pulses at a wavelength of 400 and 800 nm caused by nonresonant interaction with an ultrashort THz pulse in LiNbO 3 crystal. The maximum polarization rotation and ellipticity was measured to be ∼ 6% and ∼ 8% at the internal angle of ∼ 8.5 • between the THz pulse and a 400 nm visible probe. This effect is modelled by solving the wave propagation equation, and analytical expressions show that an interplay between distinct phase-and group-matching conditions for visible and THz electromagnetic fields determines the overall conversion efficiency. Being in excellent agreement with theoretical calculations, our experimental findings pave the way to the design of ultrafast and efficient miniaturized electrooptical devices for pulse shaping operating in the multi-THz range.

Funding

Campus France; Rgion Pays de la Loire (NNN-Telecom, Ultrasfast Acoustics in Hybrid Magnetic Nanostructures and Echopico projects).

Figure 1 :

 1 Figure 1: (a) Schematic of the time-resolved polarization change measurement in a z-cut LiNbO 3 crystal in the frontside probing configuration. HWP, half-wave plate; QWP, quarter-wave plate. WP, Wollaston prism. BPD, balanced photodiodes. LIA, lock-in amplifier. L, samples thickness. (b) Relative change of the probe light polarization orientation as a function of the time delay between the THz pump pulse and the 400 nm probe pulse for α out = 25 • (α in = 10 • ) in the back-side probing configuration, shown by the small sketch. (c) Ultrafast transients obtained for different probe angles as a function of the time delay between the pump and the probe in the back-side probing configuration. The curves are normalized and shifted for the sake of clarity.

  The alternating time windows for the observation of copropagating and counterpropagating THz and visible pulses inside the crystal of thickness L= 1 mm (see Fig 1 (b)) are governed by group velocities, ∆τ + ≈ L c (n THz -n gr o ) and ∆τ -≈ L c (n THz + n gr o ) , (1)

Figure 2 :

 2 Figure 2: (a) Measured frequencies as a function of the probes incidence angle. Two different probing wavelengths are plotted as well as the predictions of our model for both wavelengths (dashed lines). (b) Comparison of the experimental and simulated polarization rotation transients for an angle α in = 10 • and λ o = 400 nm. The corresponding oscillations frequencies are ν + = 0.69 THz and ν -= 0.27 THz. Vertical dotted lines separate the regions with co-and counter-propagating pump and probe pulses.

where d 22 Figure 3 :

 223 Figure 3: Polarization rotation angle as a function of the measured frequency for the high-and low-frequency modes. For comparison, the experimental THz spectrum is shown in the dashed line. Inset, polarization rotation angle for the high-frequency oscillation versus the THz electric field strength for α in = 9.3 • and λ o = 400 nm in the front-side configuration.

= 2 . 7 ,

 27 agreeing with the experimental value of ≈ 3. Deviation of the numerical simulation starting at around 0.4 THz for the back-side configuration, corresponding to an angle α in ≈ 15 • (α out ≈ 38 • ), can be explained by the geometrical effect of the beams crossing in the sample which is neglected in our model.


MD Duc Dang

MD Vincent Galand

Aurelie Loirat

MD Vincent Auffret

MD Nathalie Behar

MD Philippe Mabo

MD Jean-Claude Daubert

MD Christophe Leclercq

Raphael P Martins
email: raphael.martins@chu-rennes.fr

MD Aurélie Loirat

MD, PhD Raphaël P Martins

Raphaël P Martins

Procedural safety and long-term follow-up after pacemaker implantation in nonagenarians

Keywords: Pacemaker, Nonagenarian, Complications Atrial fibrillation AV: Atrio-ventricular CCI: Charlson comorbidity index CI: Confidence interval CRT: Cardiac resynchronization therapy CRT-P: Cardiac resynchronization therapy-Pacemaker OR: Odds ratio HR: Hazard ratio

Introduction

The implantation rate of pacemakers (PM) is increasing significantly each year in Europe, reaching 933 pacemakers per million inhabitants. [1] This increase is due in part to the ageing of the population, which causes an increased risk to develop atrioventricular (AV) block and sinus node dysfunction, but also related to the expansion of cardiac resynchronization therapy (CRT) indications or His ablation for heart rate control in patients with atrial fibrillation (AF).

The mean age at device implantation is currently 80.2, 77 and 75.5 years old for single chamber, dual chamber and CRT-devices, respectively [START_REF] Tuppin | Implantation and patient profiles for pacemakers and cardioverter-defibrillators in France (2008-2009)[END_REF]. In 2015, life-expectancy at birth in Europe was 80.5 years for the general population, reaching 83.3 and 77.9 years for women and men, respectively.[3] Over the past 50 years, it has increased by about 10 years. By 2060, life expectancy is projected to be 89.1 and 84.6 years for female and male, respectively, [4] and the number of patients aged 80 and more is expected to double. Currently, only few studies specifically reported the long-term outcome of PM implantation in elderly patients.

Mandawat et al evaluated the short-term mortality and complications of PM implantation in elderly patients, reporting 1.87% and 6.31% mortality and complications rates in nonagenarians, respectively. [START_REF] Mandawat | Safety of pacemaker implantation in nonagenarians: an analysis of the healthcare cost and utilization project-nationwide inpatient sample[END_REF] Also, Udo et al studied outcome of PM recipients aged > 80 and reported a cumulative 5-year survival of around 50% after implantation, with a 18.1% complication rate. [START_REF] Udo | Long-term outcome of cardiac pacing in octogenarians and nonagenarians[END_REF] More recently, Loirat et al described short and long term outcomes of pacemaker replacement in nonagenarians, reporting AF and non-physiological pacing as predictors of mortality. [START_REF] Loirat | Pacemaker replacement in nonagenarians: Procedural safety and long-term follow-up[END_REF] However, no studies specifically evaluated the short and long-term outcomes of PM primoimplantation in nonagenarian. Therefore, in the present study, we aimed at analyzing the procedural characteristics, survival rate and causes of deaths in nonagenarians.

Accepted Article

Methods

Study population and data collection

Consecutive patients aged > 90 yo referred to our tertiary centre for device implantation from January 2004 to December 2017 were retrospectively enrolled. The study was approved by local ethical committee and all patients gave their informed consent to participate.

Clinical information was obtained from patients' medical records, which included patient demographics, medical history and medication use. "Physiological pacing" was defined as the implantation of a dual chamber PM or CRT in patients in sinus rhythm and single chamber PM for patients in atrial fibrillation, while "non-physiological pacing" was defined as the implantation of a VVI chamber device in patients in sinus rhythm. The Charlson comorbidity index (CCI), a validated score to assess patients' comorbidities, was evaluated using dedicated scales available online. [START_REF] Charlson | Charl-son Comorbidity Index[END_REF][START_REF] Hall | An electronic application for rapidly calculating Charlson comorbidity score[END_REF] Various CCI have been proposed, depending on the number of variables included. We decided, as previously performed by Mandawat et al in their study about elderly pacemaker recipients, to use the one not including age, since all our patients were > 90 yo. [START_REF] Mandawat | Safety of pacemaker implantation in nonagenarians: an analysis of the healthcare cost and utilization project-nationwide inpatient sample[END_REF] Procedural characteristics of the device implantation were recorded, including indication of pacing, the type of PM implanted, the hospital length stay, and the procedural complications.

Procedural complications included lead-related re-interventions for displacement or dysfunction, hematoma requiring re-intervention, pneumothorax requiring drainage, hemothorax, pericardial effusion due to cardiac perforation, and pacemaker-related systemic infections or endocarditis.

Follow-up and outcomes

Accepted Article

Clinical follow-up data were obtained from clinical visits, or telephone interviews of patients or their families, general practitioners or nurses. The primary clinical endpoint was total mortality over the follow-up period.

Causes of death were obtained through hospital discharge notes, inquiries made with the family, the general practitioner or nursing homes, and classified using the International Statistical Classification of Diseases and Related Health Problems classification (ICD-10), as cardiovascular cause (I00-I99), pulmonary cause (J00-J99), digestive cause (K00-K93), neoplasic cause (C00-D48), renal cause (N00-N99), due to a multiple organ dysfunction (R65-10) or from an unknown origin (R99). Deaths were classified as unknown when no specific cause could be identified. Patients lost to follow-up were censored as alive the day of the last visit. Secondary endpoints included procedure-related and in-hospital complications.

Statistical analyses

Data are summarized as frequencies and percentages for categorical variables. Quantitative variables are expressed as mean ± standard deviation or median (inter quartile range (IQR)) for non-normally distributed variables. Qualitative data were compared using Fisher exact test, while quantitative data were compared using Mann and Whitney test. Survival curves were estimated using Kaplan-Meier method, with log-rank tests for comparisons. The prognostic relevance of different characteristics on long-term survival was assessed in univariate and multivariate fashion using Cox's proportional hazards regression analysis. All the values with a p≤0.2 in univariate analysis were used for multivariate analysis. All tests were 2 sided at the 0.05 significance level. All statistical analyses were carried out with the SPSS for Windows, version 16.0 (SPSS Inc., Chicago, Illinois, USA).

Results

Accepted Article

Study population

From January 2004 to December 2017, 172 nonagenarian patients were referred for PM implantation. Patients' characteristics are described in Table 1. The median age of patients included was 91.9 years (IQR 90.9-93.7; from 90.0 to 101.4 yo) at the time of PM implantation, and 67 (39.8%) were male. A total of 45 patients (26.2%) were living in nursing homes at the time of implantation and the median CCI was 2.0 (1.0-3.5).

The main indication for implantation was high degree AV block (144 patients, 83.7%). The other indications were sinus node dysfunction, sick-sinus syndrome, high rate AF with AV junction ablation, carotid sinus hypersensitivity and CRT for heart failure.

Procedural characteristics and short-term outcome

Procedures were short, lasting for a median time of 50.0 (IQR 35.0-60.0) minutes, and all were performed with local anesthesia using mild sedation. Median hospital stay was 3.5 days (IQR 2.0-7.0, from 1 to 30 days). Most of the patients had single chamber PM implanted (143 patients, 83.1%) and pacing was considered as "physiologic" only for 58 (33.7%), since most of the patients were in sinus rhythm on time of implantation (136 patients, 79.1%) and devices implanted mostly VVI pacemakers (83.1%).

To note, at the time of device implantation, many of the patients were under antithrombotic therapy with anticoagulant, antiplatelet therapies or both (25.0%, 47.7% and 4,7% respectively), and the median number of drugs taken by the patients was 5.0 (3.0-7.0).

Regarding the complications of the procedure (Table 2), four patients had a pocket hematoma, none of them requiring a surgical revision. Three patients had a lead displacement requiring a redo intervention, and one got a pneumothorax. One patient had a hemothorax needing a surgical drainage and a prolonged hospitalization (24 days).

Accepted Article

Twenty-six patients (16.2%) had post-procedural complications, non-related to the implantation (Table 2): 9 patients had congestive heart failure (8.0%) regressive after medical therapy, but leading to one death. The other complications were transient confusion for 2 patients, pneumonia for 2 patients, and renal failure for one patient. A 97 years old woman had a femoral fracture after a fall following PM implantation and one patient in AF had an embolic stroke. For all these patients, the complication extended the duration of hospital stay to 6.5 days (IQR 3.0-9.0, p<0.001). There was a significant difference in CCI between nonagenarians with or without procedure complication (Table 1). Indeed, as shown in Figure 1, panel A, the higher the CCI, the higher the risk of per-or post-procedural complications.

Furthermore, the CCI was found to be the only predictor of post-implantation complications (Table 3) in multivariate analysis (odds ratio (OR) = 1.33; 95% confidence interval (CI):

(1.05-1.69) per 1 unit increase, p= 0.02).

Four nonagenarians (2.3%) died before leaving hospital: two patients of severe geriatric cachexia, one of a myocardial infarction and one of a cerebral hemorrhage.

Long-term follow-up

The median time of follow-up was 22.5 months (IQR 7.1-37.1). Twelve patients (6.7%) were lost of follow-up, and censored as alive the day of the last visit.

During the follow-up, 94 patients died (54.7%), and one patient was still alive after more than 9 years of follow-up. Causes of death are described in Table 2. The median time of survival was 22.5 months (95% CI 7.3-38 months). The survival at 1, 2 and 5 years were 82.9% (95% CI: 76.0-88.0%), 73.7% (95% CI: 65.7-80.1%) and 37.5% (95% CI: 27.5-47.5%), respectively. Seventeen patients (18.1%) died from a cardiovascular cause, mainly due to heart failure (14 patients, among which pacing was considered "physiologic" in only 6).

Despite inquiries made with the general practitioner or medical service in case of patients

Accepted Article

living in nursing homes, 52 deaths remained of unknown cause (55.3%). To note, one patient with an aortic mechanic valve had an endocarditis (Streptococcus gallolyticus) 3 months after the implantation of the PM, leading to patients' death few weeks later.

Predictors of mortality

Predictors for all-cause mortality in univariate and multivariate analysis are shown in Table 3.

In univariate analysis, there was an increased mortality risk depending on a history of AF (Hazard Ratio (HR) = 1.80; 95%CI: 1.17-2.77, p= 0.08), on the presence of an ischemic or a valvular cardiomyopathy (HR = 2.48, 95% CI: 1.18-5.24 p= 0.0.17 and HR = 2.13, 95% CI:

1.07-4.26, p= 0.032) and on complications after PM procedure (HR = 2.17, 95% CI: 1.31-3.61, p= 0.003). Moreover in univariate analysis, the number of medications (HR = 1.12, 95% CI: 1.03-1.22, p= 0.01) per each additional treatment, the CCI (HR = 1.19 per unit increase, 95% CI: 1.06-1.33, p= 0.003) and AF (HR = 1.80, 95% CI: 1.17

Discussion

Main results

The main findings of this study are the following: 1) PM implantation in nonagenarians is a straightforward procedure in patients > 90 yo, but carries a significant risk of peri-procedural and post-procedural complications; 2) Many comorbidities can affect post-operative period Accepted Article and prolong the hospitalization; 3) The CCI is a predictive factor of post-operative complications 4) Post-operative complications and AF are predictors of mortality.

Nonagenarians in the general population

The percentage of nonagenarians is expected to increase in next decades, and according to the American Social Security Administration, one out of every four 65-year-olds today will live past age 90, and one out of 10 will live past 95. [10] In the United States, the number of nonagenarians has increased from approximately 230,000 in 1960 to approximately 1.8 million in 2010, and in the five biggest countries in the European Union (Germany, France, the United Kingdom, Italy, Spain) the number has increased from approximately 250.000 to 1.6 million. [START_REF] Thinggaard | Survival prognosis in very old adults[END_REF] This frail population is at high risk of symptomatic high degree AV block and sinus node dysfunction requiring PM implantation.

Safety of the procedure

Many short-term complications are described after PM implantation like hematoma, devicerelated infection, lead dislodgment, device extrusion or pericardial effusion. [START_REF] Udo | Long-term outcome of cardiac pacing in octogenarians and nonagenarians[END_REF] They affect approximately up to 9.5% of device recipients. [START_REF] Kirkfeldt | Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark[END_REF] Kirkfeldt et al analyzed all procedure of electronic device implantations in Denmark regardless of age. Lead related re-intervention was the most common complication (2.4%). [START_REF] Kirkfeldt | Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark[END_REF] In elderly patients (> 80 yo), the risk of any lead-related re-intervention was lower than for patients between 60 and 79 yo (1% vs 3.1%, p< 0.001).Similarly, Udo et al reported a significant 9.8% and 6.9% rate of complications in octagenarians, mostly lead-related, within 2 months and during long-term follow-up, respectively. [START_REF] Udo | Long-term outcome of cardiac pacing in octogenarians and nonagenarians[END_REF] Similarly, very elderly patients did not seem to have more complications than younger patients in other studies. [START_REF] Kirkfeldt | Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark[END_REF][START_REF] Eberhardt | Long term complications in single and dual chamber pacing are influenced by surgical experience and patient morbidity[END_REF] On the contrary, Ozcan et al demonstrated that the complication rate for elderly patients who had a permanent PM implantation was statistically Accepted Article lower than in patients who were < 70 yo. [START_REF] Ozcan | Pacemaker implantation complication rates in elderly and young patients[END_REF] However, in the largest epidemiologic study published so far about PM implantations, in the nonagenarians subgroup, including more than 12 000 patients from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample administrative database, Mandawat et al demonstrated a 1.87% and 6.31% mortality and complication rates, respectively, modestly but significantly more than in septuagenarians and octogenarians. These frail patients also had a significantly longer hospital stay than younger patients, whose cost was estimated to be more than $41 000. Severe comorbidities and older age were strong predictors of mortality. [START_REF] Mandawat | Safety of pacemaker implantation in nonagenarians: an analysis of the healthcare cost and utilization project-nationwide inpatient sample[END_REF] Various parameters may explain the higher rate of complications observed in elderly patients, including tortuous venous anatomy making lead placement sometimes challenging. [15] This may explain the higher rate of pneumothorax observed in the PASE trial in patients aged > 75 years. [START_REF] Lamas | Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker selection in the elderly investigators[END_REF] Elderly patients also have a thinner right ventricular wall, increasing the risk of cardiac perforation. Ventricular lead should be carefully placed to reduce this risk. In our study, 5.2% had early complications. No hematoma requiring re-intervention was noted during the follow-up period. Three patients had a lead displacement requiring a redo intervention and one had a hemothorax needing a surgical drainage and a prolonged hospitalization. Twenty-six patients (15.1%) had postprocedural complications, non-related to the implantation. This important rate of complications was related to nonagenarians' fragility, directly correlated to the CCI. As described, nearly 50% of the nonagenarians with a CCI between 6 and 8 had post procedural complication. For all these patients, the complication extended the duration of hospital stay.

Long-term survival

Among the study population, 92 patients (54.7%) died, mainly from unknown or cardiovascular causes, and survival rates were 82.9%, 73.7% and 37.5% after 1, 2 and 5 years, respectively, and median time of survival was 22.5 (95%CI: 7.1-37.1 months). These survival Accepted Article rates are quite similar to what has been previously described by Udo et al. in a population of octogenarians and nonagenarians implanted with PMs (86, 75 and 49% after 1, 2 and 5 years), [START_REF] Mandawat | Safety of pacemaker implantation in nonagenarians: an analysis of the healthcare cost and utilization project-nationwide inpatient sample[END_REF] In a prospective community-based study, Formiga et al found that better cognitive status and lesser comorbidities (evaluated by the CCI) were the best predictors to identify which nonagenarians will die after a 5-year follow-up period. [START_REF] Formiga | Predictors of long-term survival in nonagenarians: the NonaSantfeliu study[END_REF] In our study univariable analysis showed that CCI, number of medication, AF and complications during hospitalization are predictors of mortality. In multivariable analysis, the CCI was the only predictive factor of post procedure complications. AF and complications were significant predictive factors of mortality for nonagenarians.

Pacing mode in nonagenarians

The optimal pacing mode has been, for a while, a matter of debate. In 2005, the United Kingdom Pacing and Cardiovascular Events (UKPACE) study showed that in elderly (> 75 yo) patients with high degree AV block, the pacing mode (VVI or DDD) did not influence the rate of deaths from all causes and the incidence of cardiovascular events.[18] Healey et al. published a meta-analysis about pacing modes to analyze whether an atrial-based pacing mode was associated with better long-term outcomes in device recipients, including UKPACE[18] and 4 large studies (CTOPP, [START_REF] Kerr | Canadian Trial of Physiological Pacing: Effects of physiological pacing during long-term follow-up[END_REF] MOST, [START_REF] Lamas | Ventricular pacing or dual-chamber pacing for sinus-node dysfunction[END_REF] PASE [START_REF] Lamas | Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators[END_REF] and the Danish trial [START_REF] Andersen | Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome[END_REF][START_REF] Andersen | Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome[END_REF]). The authors showed that compared with ventricular pacing, the use of atrialbased pacing does not improve survival or reduce heart failure or cardiovascular death. Jahangir et al [START_REF] Jahangir | Relation between mode of pacing and long-term survival in the very elderly[END_REF] describe that in very elderly patients (≥ 80 years), the mode of pacing was not found to be a predictor of all-cause mortality. However, these results were contradicted by Krzemień-Wolska et al in a recent paper [START_REF] Krzemień-Wolska | Prognostic Factors in Patients with an Implanted Pacemaker after 80 Years of Age in a 4-Year Follow-Up[END_REF] that showed that DDD mode pacing decreased mortality among patients aged >80 years in long-term follow-up, and by Loirat et al. that found that non-physiological pacing was a predictor of mortality in nonagenarians scheduled

Accepted Article

for PM replacement, [START_REF] Loirat | Pacemaker replacement in nonagenarians: Procedural safety and long-term follow-up[END_REF] In our study, only 58 patients (33.7%) had a physiological stimulation, but there was no significant difference in terms of mortality between nonphysiological stimulation in univariate analysis neither in multivariate analysis.

Limitations

We acknowledge some limitations in our study. Our analysis was performed as a retrospective review of a cohort of patients, with the inherent limitations of such studies (i.e. some patients were lost of follow-up). Due to the retrospective nature of the study, only in-hospital complications could be carefully collected and described. Out-of-hospital complications, except device-related endocarditis in 1 patient, could not be gathered and detailed in the manuscript. Furthermore, the limited number of patients may not allow a precise determination of predictive factors of mortality.

As stated above, some patients developed heart failure during the study period. However, none of them were scheduled for CRT-P implantation, and all were treated medically.

Although this attitude is questionable, patients were considered too frail and/or too elderly to undergo a left ventricular lead implantation, and so, we cannot draw conclusions about device upgrade in nonagenarians. Moreover, a potential deleterious effect of right ventricular pacing on left ventricular function cannot be excluded in these patients. The pacing burden was not collected in our study, so we cannot incriminate with certainty the pacing as the cause of heart failure development.

The rate of VVI, DDD or other device type was similar among groups (p=0.926). One would probably expect higher risk of complications in patients with more than one single lead implanted, but our study was probably underpowered to show such effect.

Accepted Article

Lastly, despite inquiries made with the general practitioner or medical service in case of nursing homes, 52 (55.3%) deaths remained from unknown cause, patients for whom the devices were not interrogated post-mortem.

Conclusion

PM implantation in nonagenarians is a straightforward procedure, but carries a significant risk of complications occurring during the hospitalization. Many comorbidities-related complications can occur in this old and frail population, that eventually major the risk of mortality.

Accepted Article

  -2.77, p = 0.008) were significant predictors of mortality. In multivariate analysis, a complication during hospitalization (OR = 4.04, 95% CI: 1.79-9.11, p = 0.001) and a history of AF (OR = 1.63, 95% CI: 1.02-2.63, p = 0.043) were the only predictive factors of mortality. Neither the other comorbidities nor CCI were predictors of mortality. Kaplan-Meier survival curves depending on the occurrence of complications are shown in the figure, panel B.

Figure 1 .

 1 Figure 1. Complication rate depending of Charlson comorbidy index (panel A) and Kaplan

Table Legends Table 1 . Characteristics and comparison between nonagenarians with and without complication during hospitalization. AF

 Legends1

	: Atrial fibrillation; AV: Atrio-ventricular; CRT-P: Cardiac
	resynchronization therapy-pacemaker.

Table 2 . Procedure and in-hospital related complications, mortality and causes of death during the follow-up Table 3. Cox regression for all-cause mortality and logistic regression for all-cause complications in pacemaker recipients above 90 years of age.

 2

	HR= Hazard ratio ; OR= Odds ratio *Per each additional treatment, reference : 1; ** Per 1 unit increase ; † Per
	1g/dL increase

Table 1 . Characteristics and comparison between nonagenarians with and without complication during hospitalization

 1 . AF: Atrial fibrillation; AV: Atrio-ventricular; CRT-P: Cardiac resynchronization therapy-pacemaker.

		General population N=172	No complication N=136	Complication N=36	p
	Age (years)	91.9 (90.9-93.7)	92.1 (90.9-94.1)	91.5 (90.9-93.4)	0.584
	Male. n (%)	67(39.0%)	54 (39.7%)	13 (36.1%)	0.593
	Patients living in nursing home. n (%)	45 (26.2%)	36 (26.5%)	9 (25.0%)	0.972
	Body mass index, (kg/m²)	23.0 (21.1-25.9)	23.1 (21.1-25.8)	22.4 (20.8-26.0)	0.693
	Indication of implantation. n (%)
	High degree AV block	144 (83.7%)	114 (82.8%)	30 (83.3%)
	Sinus node dysfunction Sick-sinus syndrome High rate AF with AV junction ablation Carotid sinus hypersensitivity CRT-P for heart failure Type of PM. n (%) Single chamber VVI Dual chamber DDD Single chamber AAI VDD CRT-P Physiologic stimulation. n (%) Subclavian puncture. n (%) Duration of procedure (minutes) Mean hospital stay (days) Heart rhythm at the time of implantation. n (%) Sinus rhythm AF Cardiomyopathy. n (%) Valvular Ischemic Hypertrophic Primary dilated Tachycardia-induced cardiomyopathy Pulmonary hypertension Unknown (no TTE performed) Comorbities. n (%) History of AF Diabetes Mellitus Hypertension History of stroke Heart failure Valvular disease Coronary artery disease Cardiac surgery Median Charlson comorbidity index Charlson comorbidity index 0 1 2 3 4 5 6 7 8 Treatments. n (%) Accepted Article No antithrombotic treatment	14 (8.1%) 8 (4.7%) 4 (2.3%) 1 (0.6%) 1 (0.6%) 143 (83.1%) 26 (15.1%) 1 (0.6%) 1 (0.6%) 1 (0.6%) 58 (33.7%) 61 (35.5%) 50.0 (35.0-60.0) 3.5 (2.0-7.0) 136 (79.1%) 36 (20.9%) 35 (20.3%) 31 (18.0%) 14 (8.1%) 8 (4.7%) 1 (0.6%) 1 (0.6%) 48 (27.9%) 58 (33.7%) 17 (9.9%) 107 (62.2%) 29 (16.9%) 56 (32.6%) 43 (25.0%) 41 (23.8%) 15 (8.7%) 2.0 (1.0-3.5) 33 (19.2%) 37 (21.5%) 25 (14.5%) 34 (19.8%) 21 (12.2%) 14 (8.1%) 1 (0.5%) 6 (1.7%) 1 (0.5%) 55 (32.0%)	10 (7.4%) 7 (5.2%) 3 (2.2%) `1 (0.74%) 1 (0.74%) 112 (82.4%) 21 (15.4%) 1 (0.7%) 1 (0.7%) 1 (0.7%) 47 (34.6%) 51 (37.5%) 49.0 (35.0-60.0) 3.0 (2.0-6.0) 107 (78.7%) 29 (21,3%) 28 (20.6%) 23 (16.9%) 11 (8.1%) 7 (5.2%) 1 (0.7%) 1 (0.7%) 35 (25.7%) 45 (33.1%) 13 (9.6%) 84 (61.8%) 22 (16.2%) 42 (30.9%) 34 (25.0%) 32 (23.5%) 10 (7.4%) 2.0 (1.0-3.0) 33 (24.3%) 28 (20.6%) 22 (16.2%) 21 (15.4%) 17 (12.5%) 11 (8.1%) 1 (0.7%) 3 (2.2%) 0 (0%) 45 (33.1%)	4 (11.1%) 1 (2.8%) 1 (2.3%) 0 (0%) 0 (0%) 31 (86.1%) 5 (13.9%) 0 (0%) 0 (0%) 0 (0%) 11 (30.6%) 10 (27.8%) 50.0 (38.5-70.0) 6.5 (3.0-9.0) 29 (80.6%) 7 (19.4%) 7 (19.4%) 8 (22.2%) 3 (8.3%) 1 (2.8%) 0 (0.0%) 0 (0.0%) 13 (36.1%) 13 (36.1%) 4 (11.1%) 23 (63.9%) 7 (19.4%) 14 (38.9%) 9 (25.0%) 9 (25.0%) 5 (13.9%) 3.0 (1.5-4.0) 0 (0%) 11 (29.7%) 3 (8.1%) 13 (35.1%) 4 (10.8%) 3 (8.1%) 0 (0%) 3 (8.1%) 0 (0%) 10 (27.8%)	0.923 0.926 0.800 0.374 0.202 <0.001 0.987 0.931 0.870 0.971 0.968 0.829 0.477 0.829 0.971 0.366 0.003 0.713
	Anticoagulants	43 (25.0%)	32 (23.5%)	11 (30.6%)
	Antiplatlet agents	82 (47.7%)	65 (47.8%)	17 (47.2%)
	Association AC and AP agent	8 (4.7%)	6 (4.4%)	2 (5.6%)
	Number of medications	5.0 (3.0-7.0)	5.0 (3.0-7.0)	6.5 (4.5-8.0)	0.02
	Blood work
	Hémoglobin level (g/dl)	12.2 (11.3-13.0)	12.2±1.4	11.8±1.7	0.166
	Creatinin level (µmol/l)	102.5 (80.0-132.0)	101.0 (81.0-131.5)	111.0 (73.8-143.8)	0.543

Table 2 . Procedure and in-hospital related complications, mortality and causes of death during the follow-up

 2

	Accepted Article

Table 3 . Cox regression for all-cause mortality and logistic regression for all-cause complications in pacemaker recipients above 90 years of age.

 3

	Cox regression for mortality	Univariate HR (95% CI)	p	Multivariable HR (95% CI)	p
	Male sex	1.37 (0.90-2.08)	0.14	0.96 (0.60-1.55)	0.87
	Physiological pacing	1.55 (0.995-2.44)	0.052	1.12 (0.67-1.87)	0.67
	Cardiomyopathy		0.09		0.27
	Ischemic	2.48 (1.18-5.24)	0.017	2.09 (0.94-4.66)	0.07
	Valvular	2.13 (1.07-4.26)	0.032	1.94 (0.93-4.04)	0.08
	Other	1.79 (0.96-3.35)	0.069	1.68 (0.88-3.20)	0.12
	Atrial fibrillation	1.80 (1.17-2.77)	0.008	1.63 (1.02-2.63)	0.043
	Prior stroke	1.53 (0.92-2.54)	0.10	1.40 (0.78-2.51)	0.26
	Complication during index hospitalization	2.17 (1.31-3.61)	0.003	4.04 (1.79-9.11)	0.001
	Number of medications	1.12 (1.03-1.22)*	0.01	1.06 (0.97-1.16)*	0.24
	Charlson score	1.19 (1.06-1.33)**	0.003	1.08 (0.95-1.24) **	0.24
	Time*complications interaction	-	-	0.96 (0.92-1.002)	0.059
	Logistic regression for complications	Univariate OR (95% CI)	p	Multivariable OR (95% CI)	p
	Number of medications	1.17 (1.02-1.34)*	0.022	1.10 (0.94-1.29)*	0.22
	Charlson score	1.35 (1.11-1.64)**	0.003	1.33 (1.05-1.69)**	0.02
	Hemoglobin on admission	0.84 (0.65-1.09) †	0.19	0.95 (0.71-1.27) †	0.72
	Sub-clavian approach	0.55 (0.24-1.25)	0.15	0.55 (0.22-1.36)	0.20

HR= Hazard ratio ; OR= Odds ratio *Per each additional treatment, reference : 1; ** Per 1 unit increase ; † Per 1g/dL increase