Abstract: The present disclosure relates to a method of protein structure and amino acid residue interaction prediction based on saturation suppressor mutagenesis screening of a protein of interest. The method of the instant disclosure can be adapted for multi-protein complexes, and is useful where crystal structure of a protein of interest is not available.

Abstract: The present disclosure relates to a method of protein structure and amino acid residue interaction prediction based on saturation suppressor mutagenesis screening of a protein of interest. The method of the instant disclosure can be adapted for multi-protein complexes, and is useful where crystal structure of a protein of interest is not available.

Abstract: Diastolic function is monitored within a patient based on dynamic cardiogenic impedance as measured by a pacemaker or other implantable medical device. In one example, the device uses ventricular cardiogenic impedance values to detect E-wave parameters representative of passive filling of the ventricles. Atrial cardiogenic impedance values are used to detect A-wave parameters representative of active filling of the ventricles. Diastolic function is then assessed or evaluated based on the E-wave and A-wave parameters. Various functions of the implantable device are then controlled based on the assessment of diastolic function, such as by adjusting atrioventricular delay parameters to improve diastolic function. In some examples, the detection of E- and A-wave parameters is achieved by aligning impedance signals to atrial activation, and separately to ventricular activation, during asynchronous VOO pacing or while artificially inducing a 2:1 block.

Abstract: Diastolic function is monitored within a patient based on dynamic cardiogenic impedance as measured by a pacemaker or other implantable medical device. In one example, the device uses ventricular cardiogenic impedance values to detect E-wave parameters representative of passive filling of the ventricles. Atrial cardiogenic impedance values are used to detect A-wave parameters representative of active filling of the ventricles. Diastolic function is then assessed or evaluated based on the E-wave and A-wave parameters. Various functions of the implantable device are then controlled based on the assessment of diastolic function, such as by adjusting atrioventricular delay parameters to improve diastolic function. In some examples, the detection of E- and A-wave parameters is achieved by aligning impedance signals to atrial activation, and separately to ventricular activation, during asynchronous VOO pacing or while artificially inducing a 2:1 block.

Abstract: Methods and systems are provided to deliver a neural stimulation therapy to treat apnea episodes. The methods and systems detect a respiratory pattern of a patient and identify a type associated with the respiratory pattern. A sleep stage is detected that the patient is experiencing and the method and system identify when the sleep stage warrants therapy. When the respiratory pattern corresponds to an apnea episode (AE) and the sleep stage warrants therapy, the methods and systems deliver an apnea episode terminating neuro-stimulation (AET-NS) therapy configured to terminate the AE. A type of AE therapy that is delivered may be based on the sleep stage that was detected. The methods and systems may determine whether the AET-NS therapy successfully terminated the AE, and, if not, adjust the AET-NS therapy and deliver a new AET-NS therapy.

Abstract: Methods and systems are provided to deliver a neural stimulation therapy to treat apnea episodes. The methods and systems detect a respiratory pattern of a patient and identify a type associated with the respiratory pattern. A sleep stage is detected that the patient is experiencing and the method and system identify when the sleep stage warrants therapy. When the respiratory pattern corresponds to an apnea episode (AE) and the sleep stage warrants therapy, the methods and systems deliver an apnea episode terminating neuro-stimulation (AET-NS) therapy configured to terminate the AE. A type of AE therapy that is delivered may be based on the sleep stage that was detected. The methods and systems may determine whether the AET-NS therapy successfully terminated the AE, and, if not, adjust the AET-NS therapy and deliver a new AET-NS therapy.

Abstract: Methods, systems and devices described herein can be used for automatically adjusting one or more cardiac resynchronization therapy (CRT) pacing parameters (and more generally stimulation parameters), to achieve a long term reduction in left ventricular (LV) diastolic pressure (and more generally, preload) of a heart failure (HF) patient. A reduction in LV diastolic pressure is indicative of a reduction in preload (the force of blood the fills the left ventricle), which is typically indicative of an improvement in a patient's HF condition. In accordance with certain embodiments, when a set of stimulation parameters is tested, the set is tested for a period that is sufficiently long enough to allow the patient's compensatory mechanisms to react to the set of stimulation parameters and achieve a substantially steady-state LV diastolic pressure corresponding to the using the set of stimulation parameters.

Abstract: Methods, systems and devices described herein can be used for automatically adjusting one or more cardiac resynchronization therapy (CRT) pacing parameters (and more generally stimulation parameters), to achieve a long term reduction in left ventricular (LV) diastolic pressure (and more generally, preload) of a heart failure (HF) patient. A reduction in LV diastolic pressure is indicative of a reduction in preload (the force of blood the fills the left ventricle), which is typically indicative of an improvement in a patient's HF condition. In accordance with certain embodiments, when a set of stimulation parameters is tested, the set is tested for a period that is sufficiently long enough to allow the patient's compensatory mechanisms to react to the set of stimulation parameters and achieve a substantially steady-state LV diastolic pressure corresponding to the using the set of stimulation parameters.

Abstract: A method and system are provided for characterizing chamber specific function. The method and system comprise collecting cardiac signals associated with asynchronous timing between first and second chambers of the heart; collecting dynamic impedance (DI) data along a chamber-specific function (CSF) vector to form a DI data set, the DI data set collected during a collection window that is temporally aligned based on a timing feature of interest (FOI); repeating the collection operations over multiple cardiac cycles (CC) to obtain an ensemble of DI data sets; and combining the ensemble of DI data sets to form a composite DI data set that is coupled to a chamber functional mechanic of interest (FMOI) associated with the first chamber and decoupled from functional mechanics associated with the second chamber; and analyzing the composite DI data set to obtain a CSF indicator associated with the chamber FMOI of the first chamber.

Abstract: A renal denervation system includes a renal denervation catheter and a flow determining system. The renal denervation catheter includes a plurality of ablation members positioned at a distal end portion thereof. The renal denervation catheter is insertable into a renal artery. The flow determining system includes a processor and first and second flow determining members spaced apart on the renal denervation catheter. The processor is configured to determine a change in blood flow through the renal artery resulting from a renal denervation procedure using the renal denervation catheter in response to input from the first and second flow determining members.

Abstract: A method and system are provided for characterizing cardiac function. The method and system comprise collecting cardiac signals associated with electrical or mechanical behavior of a heart over at least one cardiac cycle; identifying a timing feature of interest (FOI) from the cardiac signals; collecting dynamic impedance (DI) data over at least one cardiac cycle (CC), designated by the timing FOI, along at least one of i) a venous return (VR) vector or ii) a right ventricular function (RVF) vector; and analyzing at least one morphologic characteristic from the DI data based on at least one of i) a VR-DI correlation metric to obtain a VR indicator associated with the CC or ii) a RVF-DI correlation metric to obtain a RVF indicator associated with CC.

Abstract: Methods, systems and devices described herein can be used for automatically adjusting one or more cardiac resynchronization therapy (CRT) pacing parameters (and more generally stimulation parameters), to achieve a long term reduction in left ventricular (LV) diastolic pressure (and more generally, preload) of a heart failure (HF) patient. A reduction in LV diastolic pressure is indicative of a reduction in preload (the force of blood the fills the left ventricle), which is typically indicative of an improvement in a patient's HF condition. In accordance with certain embodiments, when a set of stimulation parameters is tested, the set is tested for a period that is sufficiently long enough to allow the patient's compensatory mechanisms to react to the set of stimulation parameters and achieve a substantially steady-state LV diastolic pressure corresponding to the using the set of stimulation parameters.

Abstract: A method and system are provided to analyze valve related timing and monitor heart failure. The method and system comprise collecting cardiac signals associated with an atrial chamber of interest; collecting dynamic impedance (DI) data along an atria-function focused (AFF) vector to form a DI data set, the DI data set including information corresponding to a mechanical function (MF) of a valve associated with the atrial chamber of interest; identifying, from the cardiac signals, an intra-atrial conduction timing (IACT) associated with the atrial chamber of interest; estimating an MF landmark at which the mechanical function of the valve occurs based on the DI data set; analyzing a timing delay between the MF landmark and the IACT; and adjusting a therapy, based on the timing delay, to encourage atrial contribution to ventricular filling.

Abstract: Methods and systems are provided to deliver a neural stimulation therapy to treat apnea episodes. The methods and systems detect a respiratory pattern of a patient and identify a type associated with the respiratory pattern. A sleep stage is detected that the patient is experiencing and the method and system identify when the sleep stage warrants therapy. When the respiratory pattern corresponds to an apnea episode (AE) and the sleep stage warrants therapy, the methods and systems deliver an apnea episode terminating neuro-stimulation (AET-NS) therapy configured to terminate the AE. A type of AE therapy that is delivered may be based on the sleep stage that was detected. The methods and systems may determine whether the AET-NS therapy successfully terminated the AE, and, if not, adjust the AET-NS therapy and deliver a new AET-NS therapy.

Abstract: An implantable medical device, comprised of at least one lead configured to be located proximate to a heart, the at least one lead including electrodes, at least a portion of the electrodes configured to sense cardiac activity. A therapy module configured to control delivery of pacing pulses in accordance with a therapy timing and based on the cardiac sensed activity sensed. Cardiac impedance (CI) sensor circuitry configured to be coupled to at least a first combination of the electrodes to sense cardiac impedance (CI), the CI sensor circuitry generating an impedance data stream associated with a corresponding CI sensing vector.

Abstract: Methods, systems and devices described herein can be used for automatically adjusting one or more cardiac resynchronization therapy (CRT) pacing parameters (and more generally stimulation parameters), to achieve a long term reduction in left ventricular (LV) diastolic pressure (and more generally, preload) of a heart failure (HF) patient. A reduction in LV diastolic pressure is indicative of a reduction in preload (the force of blood the fills the left ventricle), which is typically indicative of an improvement in a patient's HF condition. In accordance with certain embodiments, when a set of stimulation parameters is tested, the set is tested for a period that is sufficiently long enough to allow the patient's compensatory mechanisms to react to the set of stimulation parameters and achieve a substantially steady-state LV diastolic pressure corresponding to the using the set of stimulation parameters.

Abstract: A method and system are provided for characterizing chamber specific function. The method and system comprise collecting cardiac signals associated with asynchronous timing between first and second chambers of the heart; collecting dynamic impedance (DI) data along a chamber-specific function (CSF) vector to form a DI data set, the DI data set collected during a collection window that is temporally aligned based on a timing feature of interest (FOI); repeating the collection operations over multiple cardiac cycles (CC) to obtain an ensemble of DI data sets; and combining the ensemble of DI data sets to form a composite DI data set that is coupled to a chamber functional mechanic of interest (FMOI) associated with the first chamber and decoupled from functional mechanics associated with the second chamber; and analyzing the composite DI data set to obtain a CSF indicator associated with the chamber FMOI of the first chamber.

Abstract: A method and system are provided for determining fluid status with a central venous system of a heart. Dynamic impedance (DI) data and static impedance (SI) data are collected over multiple cardiac cycles (CC) for a persistent time period of interest (POI). The DI and SI data are collected along a central venous (CV) vector that extends through a superior vena cava (SVC). The DI and SI data are analyzed to obtain DI long-term variation (LTV) information and SI LTV information, respectively, and to detect whether the DI LTV information and the SI LTV information include decreasing persistent trends in the DI and SI data. When decreasing persistent trends are detected in the DI and SI data, an overload output is generated to indicate that the heart is experiencing a volume overload state. The DI and SI data represent a surrogate for central venous pressure.

Abstract: A method and system are provided to analyze valve related timing and monitor heart failure. The method and system comprise collecting cardiac signals associated with an atrial chamber of interest; collecting dynamic impedance (DI) data along an atria-function focused (AFF) vector to form a DI data set, the DI data set including information corresponding to a mechanical function (MF) of a valve associated with the atrial chamber of interest; identifying, from the cardiac signals, an intra-atrial conduction timing (IACT) associated with the atrial chamber of interest; estimating an MF landmark at which the mechanical function of the valve occurs based on the DI data set; analyzing a timing delay between the MF landmark and the IACT; and adjusting a therapy, based on the timing delay, to encourage atrial contribution to ventricular filling.

Abstract: Diastolic function is monitored within a patient based on dynamic cardiogenic impedance as measured by a pacemaker or other implantable medical device. In one example, the device uses ventricular cardiogenic impedance values to detect E-wave parameters representative of passive filling of the ventricles. Atrial cardiogenic impedance values are used to detect A-wave parameters representative of active filling of the ventricles. Diastolic function is then assessed or evaluated based on the E-wave and A-wave parameters. Various functions of the implantable device are then controlled based on the assessment of diastolic function, such as by adjusting atrioventricular delay parameters to improve diastolic function. In some examples, the detection of E- and A-wave parameters is achieved by aligning impedance signals to atrial activation, and separately to ventricular activation, during asynchronous VOO pacing or while artificially inducing a 2:1 block.