CN119947647A - Method for maintaining serum potassium homeostasis by subcutaneous monitoring - Google Patents

Abstract

Imbalance of potassium levels is the leading cause of death in patients undergoing dialysis. Here, a method for maintaining serum potassium homeostasis by subcutaneous monitoring is provided. An electrocardiogram (ECG) clinical manifestation for indicating the onset and presence of loss of serum potassium homeostasis in dialysis patients is maintained, and in another embodiment, arrhythmia characteristics for indicating the onset and presence of loss of serum potassium homeostasis in dialysis patients are maintained. The ECG signal of the patient's heart is continuously monitored subcutaneously based on the beat-to-beat heartbeat. The ECG signal is processed in real time into a group of ECG traces, each of which represents the net electrical activity of the heart at a given moment. For this group of ECG performances, each ECG trace is evaluated, and in another embodiment, for arrhythmia characteristics, each ECG trace is evaluated over time. When at least one of the ECG performances is identified in the ECG traces, an alarm for a medical condition is generated.

Description

Methods for maintaining serum potassium homeostasis by subcutaneous monitoring

Technical Field

The present application relates generally to medical diagnosis and treatment of serum potassium imbalance, and in particular to a method for maintaining serum potassium homeostasis by subcutaneously monitoring physiological parameters.

Background

End Stage Renal Disease (ESRD) is a medical condition affecting over 50 tens of thousands of patients in the united states. ESRD is defined as glomerular filtration rate below 15mL/min, an advanced stage of Chronic Kidney Disease (CKD) where the kidneys permanently stop functioning. CKD and its sequelae ESRD remain significant causes of reduced quality of life and premature death.

To sustain life, patients with ESRD must undergo regular dialysis or receive kidney transplants. Dialysis removes waste and excess fluid from the blood by a combination of filtration and osmosis using a dialysis solution or dialysate. There are two types of dialysis, both of which take about four to six hours, performed three times per week. Peritoneal Dialysis (PD) uses tiny blood vessels within the abdominal lining (peritoneum) as natural filters to clean the blood with the aid of dialysate. PD can be conveniently performed during sleep at home. Hemodialysis (HD) uses a semi-permeable dialyzer to filter waste products from the blood, remove excess chemicals and fluids, and equilibrate the electrolyte with the dialysate. HD requires a specialized clinic with dialysis machines and trained medical personnel.

Although life is maintained in patients with ESRD, both HD and PD are never at considerable risk to the patient's health. There is a risk of over-and under-removal of critical blood components including electrolytes, especially potassium, which is essential for normal heart function. Serum potassium homeostasis must always be kept strictly within a limited range to prevent the frequent tachycardia manifestations of various fatal arrhythmias. It is well known that narrow ranges of potassium deviations below or above about 3.5 to 5.5mEq/L over days, hours or even minutes can be fatal for patients with ESRD, depending on the extent of low or high potassium levels and any underlying heart disease that is susceptible to such potassium abnormalities.

Patients with ESRD may have a particularly high risk of sudden death if dialysis is not timely and periodically performed to remove potassium that is no longer excreted by urine. Potassium levels above 6.0mEq/L can be easily fatal if not addressed in time. Such high potassium levels in patients with ESRD (known as hyperkalemia) can occur over a short period of time (frequently after dialysis) and can have a variety of common causes, including in delayed entry dialysis regimens, under-dialysis, or all those that can lead to dehydration of the patient resulting in elevated potassium levels or acute health conditions (such as infections COVID-19 or lower gastrointestinal discomfort resulting in diarrhea). Emergency medical care is needed to combat hyperkalemia. The opposite problem is that low potassium levels (known as hypokalemia) are also common in patients with ESRD and can be fatal. Unfortunately, there is no real-time or even near real-time test method to proactively identify serum potassium imbalances in ESRD patients, other than routine pre-dialysis blood withdrawal in HD patients, which makes dialysis patients vulnerable and at risk.

Untrained observers typically do not notice a loss of serum potassium homeostasis until severe symptoms develop. However, there is a robust and well-known correlation between potassium imbalance and Electrocardiographic (ECG) changes. Both high and low potassium levels exhibited identifiable ECG changes. These ECG changes may be accompanied by specific cardiac rhythm dysfunction in the typical progression of cardiac arrhythmias, which in severe cases may indicate that the patient is at serious risk, including Sudden Cardiac Death (SCD).

These characteristic ECG performances can be displayed within minutes. This typical ECG variation seen at low potassium levels begins with the potassium concentration falling below 2.5mEq/L and is exacerbated as the level is further reduced. Also, for high potassium levels (typically above 6.0 mEq/L), as the level rises and climbs to higher and higher levels, characteristic ECG changes will be exhibited. Since ESRD patients have limited ability to maintain potassium homeostasis in the event of dialysis-induced metabolic deviations from the normal range, the risk of serum potassium abnormalities causally linked to HD or PD treatment is enormous, especially because the survival rate of patients receiving dialysis in the united states is already at world minimum, and in particular, most patients begin dialysis with overt cardiovascular disease, thus putting them at increased risk of death due to the unexpected arrhythmia or complications associated with potassium abnormalities. From R.N.Foley et al ,Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis,N.Engl.J.Med.365:1099-10,2011.

Conventional approaches focus on avoiding hypokalemia and hyperkalemia by prophylactic means and periodic blood spot testing (periodic spot blood test), but fail to address the significant and dynamic risks faced by ESRD patients at all (especially during dialysis interval periods when serum potassium imbalance of these patients may be neglected). For example, one approach suggests the use of dialysate potassium profile analysis during HD treatment, as discussed in p.h. pun and J.P.Middleton,Dialysate Potassium,Dialysate Magnesium,and Hemodialysis Risk,J.Am.Soc.Nephrol.28:3441-3451,2017. In the analysis, optimal dialysate potassium levels are selected to balance, achieving adequate potassium removal, thereby avoiding hyperkalemia during dialysis, while minimizing potential risks due to too rapid potassium reduction during dialysis. Analysis includes frequent serum potassium monitoring and flexible medical intervention if necessary. However, in practice, the analysis requires physical changes in dialysate concentration throughout the HD treatment, thus making the analysis impractical when applied to a population of general ESRD patients at risk of potassium-triggered cardiac arrest that may occur within minutes or hours of dialysis.

A similar preventive approach applies dialysate potassium conditioning algorithms to HD treatment to avoid serum dialysate mismatch and achieve safe serum potassium concentrations. Adjustment algorithms are sometimes combined with non-dialysis methods that focus on patient analysis and management strategies through dietary consultation and use of potassium-lowering drugs. However, such algorithms can at best be only prophylactic and may even potentially increase risk by failing to distinguish individual changes in pre-dialysis serum potassium levels from chronic serum potassium trends due to acute or transient conditions, thus inadvertently causing acute serum potassium imbalance.

The last method involves using a higher concentration dialysate potassium bath or lower blood and dialysate flow rates to extend HD treatment time or increase frequency. However, there are limits to available dialysis clinics that can provide either extended HD therapy or daily HD therapy, and this approach is generally less desirable for patients and dialysis providers. Furthermore, there is limited evidence that this approach has any real effect on the prevention of death caused by arrhythmias associated with potassium disorders. The rapidity of the problem of severe potassium level changes, coupled with the complexity of the disease, daily life, mental, family circumstances, physical and mental capabilities, etc., of each patient, all combine to make efforts to predict and prevent who will die, futile (especially those who live alone for PD, lack of medical supervision by the HD center staff). Furthermore, humans tend not to follow strict courses of medical action, which is a well-known weakness in the management of any chronic disease, multiplied by complex problems like ESRD. Any change in the routine arrangement only aggravates the risk of potassium imbalance. Some simple examples include binge eating, travel affected by traffic, flight cancellation, bad mood, interfering family diseases, blackout, etc. Thus, potassium levels in ESRD patients are highly dynamic, highlighting the cardiovascular death concerns in those ESRD patients with intermittent dialysis schedules, and even varying medications. From R.N. Foley et al, 1099.

Thus, there remains a need for a proactive method for identifying, diagnosing, alerting, and timely alleviating a serum potassium imbalance, particularly when patients with ESRD are medically unattended and mostly at risk, during dialysis intervals where these patients may develop dangerous low or high potassium levels in a very short period of time.

Disclosure of Invention

Death due to arrhythmia associated with serum potassium disorders is preventable. By actively monitoring the patient's ECG and proactively identifying specific ECG changes that are indicative of the onset or presence of hypokalemia and hyperkalemia, the significant and potentially fatal risks associated with hypokalemia or hyperkalemia that develop rapidly in ESRD patients can be alleviated or even completely avoided. ECG traces are analyzed in real-time by an Implantable Cardiac Monitor (ICM) to identify these specific ECG changes for indicating hyperkalemia and hypokalemia, with or without arrhythmia. Desirably, the identification of ECG changes is indicative of the occurrence of an arrhythmia. For optimal efficiency, such active monitoring should be performed at any time during the dialysis interval, and during the post-dialysis interval. Except for the possibility of monitoring during hemodialysis, patients with ESRD tend to become a period of serum potassium imbalance that is easily ignored and not resolved in nearly all periods.

An efficient form of active ECG monitoring uses a continuous ICM that can take advantage of the correlation between electrocardiographic changes and serum potassium imbalance. The ICM may provide a continuous data stream of high quality ECG signals in a wireless manner and incorporate alarms when identifiable Electrocardiographic (ECG) changes (with or without specific arrhythmias that may indicate the onset or presence of hypokalemia or hyperkalemia). The continuous data stream enables the ICM to operate without memory limitations. Other forms of ECG monitors, both implantable and cutaneous, are possible, but ICMs with continuous data flow are only able to detect potassium imbalance. Depending on the degree of abnormality, such data may be used to alert one or more of the patient, family, doctor, and Emergency Medical Service (EMS) wirelessly through an algorithm based on 24 hours/7 days per week/365 days per year (24/7/365).

In one embodiment, the microcontroller in the ICM operates under micro-program control using firmware capable of recognizing in real-time the ECG performance in the sensed ECG signals that form the ECG traces. If the ECG trace has a depressed ST segment and a prolonged QT interval (or QTU interval), possibly with a distinct U-wave, then hypokalemia exists and an emergency event is triggered. If the ECG trace has a peak T wave, there is moderate hyperkalemia and an emergency event is triggered. If the ECG trace has a wider QRS complex than normal, a peak T wave, a longer PR interval, and a lower P wave amplitude, then severe hyperkalemia exists and an emergency event is triggered. Finally, if the ECG trace has QRS complex and T wave similar to a "sine" wave without P wave, there is severe hyperkalemia and an emergency event is triggered. Other ECG performances may lead to different or complementary types of alarms.

One embodiment provides a method for maintaining serum potassium homeostasis by subcutaneous monitoring. A set of ECG performances is maintained, the ECG performances being indicative of at least one of onset and presence of a loss of serum potassium homeostasis in dialysis patients. Electrocardiographic (ECG) signals of the heart of a patient are continuously monitored subcutaneously on a beat-by-beat basis. The ECG signal is processed in real time as a set of ECG traces, where each ECG trace represents the net electrical activity of the heart at a given moment. Each ECG trace is evaluated for a set of ECG performances. Upon identifying at least one of the ECG performances in one or more of the ECG traces, an alert of the medical condition is generated.

Another embodiment provides an implantable cardiac monitor for maintaining potassium homeostasis. The implantable housing is formed in a cylindrical shape with a rounded hemispherical end cap and comprises a biocompatible material suitable for implantation into a living body. At least one pair of ECG sensing electrodes disposed on the ventral surface and on opposite ends of the implantable housing are operatively disposed about the end caps to facilitate the closest sensing of low amplitude, low frequency content cardiac action potentials generated during atrial and ventricular activation of atrial and ventricular repolarizations. An electronic circuit is disposed within the housing assembly and includes a low power microcontroller operable under the control of a modular micro-program, an ECG front end circuit interfaced with the microcontroller and configured to capture cardiac action potentials sensed by a pair of ECG sensing electrodes as an ECG signal, the ECG signal including a set of ECG traces, each ECG trace representing net electrical activity of the heart at a given moment, firmware provided as part of the micro-program including identifying ECG performances in one or more of the ECG traces based on beat-to-beat, and a non-volatile memory electrically interfaced with the microcontroller and operable to continuously store samples of the ECG signal, wherein the microcontroller generates event triggers upon the microcontroller identifying at least one of the ECG performances in one or more of the ECG traces.

Still other embodiments will become readily apparent to those skilled in the art from the following detailed description, wherein embodiments are described by way of illustration of the best mode contemplated. As will be realized, other and different embodiments are possible and many details of the embodiments can be modified in various obvious respects, all without departing from the spirit and scope thereof. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.

Drawings

Fig. 1 is a diagram illustrating by way of example a patient undergoing dialysis treatment with a Hemodialysis (HD) machine, according to one embodiment.

Fig. 2 is a graph showing by way of example the relationship between long dialysis intervals and mortality in ESRD patients.

Fig. 3 is a graph showing by way of example the relationship between hyperkalemia and chance of death within one day of moderate and severe hyperkalemia events.

Fig. 4A-4E are graphs showing by way of example the relationship between Electrocardiographic (ECG) changes and serum potassium levels.

Fig. 5 is an external perspective view illustrating an Implantable Cardiac Monitor (ICM) for maintaining potassium homeostasis according to one embodiment.

Fig. 6 is an external perspective view illustrating an Implantable Cardiac Monitor (ICM) for maintaining potassium homeostasis according to another embodiment.

Fig. 7 is a block diagram illustrating the microarchitecture of the ICM of fig. 5.

Fig. 8 is a flow chart illustrating a method for continuously monitoring an electrocardiogram for use in the ICM of fig. 5.

FIG. 9 is a flow chart showing a procedure for identifying an ECG representation in an ECG signal for use in the method of FIG. 8.

FIG. 10 is a flow chart showing a procedure for evaluating timeliness of an ECG performance used in the method of FIG. 8.

Fig. 11 is a flow chart showing patient workflow.

Fig. 12 is a flow chart showing the physician and staff workflow.

Fig. 13A-13C are schematic diagrams showing, by way of example, a patient case study presented in tabular form, wherein events with patient history and 31 day summary are indicated by the table, along with comments reflecting significant morbidity associated with patient condition.

Detailed Description

Serum potassium steady state

Electrolyte balance is vital to life and serum potassium homeostasis must be maintained strictly within a limited range to ensure proper cardiac function and to prevent the manifestation of various fatal cardiac arrhythmias. It is well known that potassium deviations below or above a narrow range of about 3.5 to 5.5mEq/L, whether cardiovascular or renal disease or due to various medications, can be fatal within days, hours or even minutes for whatever reason, depending on the extent of low or high potassium levels and the underlying heart disease that is susceptible to such abnormalities. If not addressed in time, potassium levels above 7.0mEq/L (hyperkalemia) can be easily fatal, and levels above 9.0mEq/L almost certainly lead to death. Hyperkalemia in patients with ESRD can occur in a very short period of time and has a variety of common causes including delayed entry into a dialysis session (say a delay to go to the HD dialysis center), or due to under-dialysis (as in the case of patients who shorten their PD for social or psychological reasons), or all those diseases or acute health conditions that can lead to dehydration of the patient resulting in elevated potassium levels (such as infections COVID-19, influenza, or lower gastrointestinal discomfort resulting in diarrhea). COVID-19 is particularly alarming in view of its ability to mutate rapidly, so that it is prevented from spreading futile and it is highly contagious as an airborne virus. Frailty and immunosuppressors, many of which are undergoing dialysis, are at high risk of infection COVID-19. Furthermore, although COVID-19 is of interest as a public health emergency, in practice, diagnosis and treatment of COVID-19 typically takes days during which patient potassium level changes are not detected or even ignored, as other symptoms, such as those affecting the respiratory system, such as cough, shortness of breath and sore throat, are of greatest concern.

In addition, changes in dialysate prescription or changes in drugs for other conditions (e.g., heart failure) can affect potassium metabolism and raise potassium levels to dangerous levels. Potassium levels down to below 2.5mEq/L (hypokalemia) are also common and potentially fatal in patients with ESRD. Levels below 1.5mEq/L typically lead to sudden death. Typically, the dangerously low potassium levels are due to prolonged dialysis, say due to prolonged sleep during PD, or due to the use of newly prescribed over-concentrated dialysate that is too aggressively depleted of potassium, which is originally provided to ameliorate the previously identified hyperkalemia problem.

Since the deadly potassium transition is rapid in patients with ESRD, continuous potassium monitoring is necessary to prevent disasters. There is a well-known robust correlation between potassium level reduction and elevation and specific Electrocardiographic (ECG) changes, and this correlation can be effectively exploited to quickly identify serum potassium imbalances and save patient lives. Typical ECG changes seen at low potassium levels begin with potassium concentrations falling below 2.5mEq/L and progressively increase in severity as the level further decreases. Also, for high potassium levels (typically above 6.0 mEq/L), the ECG characteristic performance will change as the level rises and climbs to higher and higher levels.

Dialysis

There are two types of dialysis, both of which take about four to six hours, performed three times per week. Dialysis is close to the normal state of human kidney health, although the kidneys are not constantly focusing on removing toxins from the blood. Peritoneal Dialysis (PD) utilizes tiny blood vessels within the peritoneum as natural filters to filter blood with the aid of a dialysis solution or dialysate that enters the abdominal space through the abdominal tube. PD is more popular than Hemodialysis (HD) because PD can be more conveniently performed at home during sleep. In the case of PD, dialysate of glucose and other elements is used to remove toxins by osmosis to extract toxins from the blood circulation in the peritoneal lining and abdominal organs, including excess potassium produced from food and normal cellular metabolism. The dialysate is then drained from the abdomen at the end of the session.

Hemodialysis (HD) is a form of dialysis that goes directly into a patient's blood vessel and uses a semi-permeable dialyzer to filter waste from the blood, remove excess chemicals and fluids, and balance electrolytes (potassium, sodium, bicarbonate, chloride, calcium, magnesium, and phosphate). Fig. 1 is a diagram illustrating by way of example a patient 11 undergoing a dialysis treatment 10 using an HD machine 12 according to one embodiment. Patient 11 is a recipient of an Implantable Cardiac Monitor (ICM) 20, such as described in U.S. patent application entitled "configurable hardware platform for physiological monitoring of a living organism" (filed on even date 15 at 7 in serial No. 16/929,390,2020, the disclosure of which is incorporated herein by reference and will be discussed further below with reference to fig. 5). ICM 20 is capable of actively identifying, diagnosing, alerting, and timely alleviating serum potassium imbalance. ICM 20 relies on the correlation between identifiable Electrocardiographic (ECG) changes accompanied by specific arrhythmias and serum potassium imbalance. Thus, ICM 20 proactively protects patient 11 from hypokalemia and the fatal sequelae of hyperkalemia at all times, including during dialysis intervals when patients with ESRD are medically unattended and most at risk, where such patients may develop dangerous high potassium levels in a very short period of time. Other forms of ECG monitors (whether implantable or dermatological) are also possible.

Dialysis treatment typically takes about four to six hours. During HD therapy, the blood pump 16 draws blood from the patient 11 into the dialysis machine 12 via the arterial channel 13 and through the dialyzer 15, which removes excess waste and fluid from the blood. The cleaned blood is then returned to the patient 11 via the vascular access 14. The dialyzer 15 is constructed of a thin fibrous material for forming a semipermeable membrane that allows smaller particles and liquids to pass through. The fresh dialysis fluid 17 passes in the opposite direction of the blood and does not actually contact the blood, whereas the spent dialysis fluid 18 containing waste leaves the dialyzer 17.

In the case of both PD and HD, the rate of potassium decline is very fast during the first hour of dialysis, since the serum-dialysate gradient is greatest. In the next two hours or so, the rate of potassium decline decreases and during the last hour, the serum potassium level remains relatively stable.

Correlation of dialysis interval with patient death

The temporal aspect of regular dialysis is critical to the health of the patient and failure of ESRD patients to strictly follow the three-day dialysis schedule during dialysis can have fatal consequences. This fatal hazard has been statistically verified. Patients are typically subjected to dialysis treatment three times per week with 1 day intervals and 2 day intervals between each session, followed by sub-acute post-dialysis rebalancing and retarded accumulation of the same fluid and electrolyte during the dialysis intervals, with 1 day intervals and 2 day intervals between each session. In particular, it has been found that a2 day interval reflects an increased risk of cardiovascular complications and death. Note that dialysis is performed on day 1, typically on monday, after a 2-day interval, possibly at a later time of the day, as is the case with peritoneal dialysis. Fig. 2 is a graph showing by way of example a relationship 30 between a long dialysis interval 31 and mortality 32 of an ESRD patient. The x-axis 31 reflects the dialysis interval, where HD1 represents the day of the first dialysis in a week, HD1+1 represents the day after the first dialysis, and so on. The y-axis 32 reflects mortality of ESRD patients due to total cause 33, cardiac cause 34, infectious cause 35, and vascular cause 36, respectively. One study found that on the day after a long dialysis interval, on HD1, total cause mortality was 22.1 per 100 people per year (relative to 18.0 per 100 people per year), mortality from cardiac causes was 10.2 (relative to 7.5), mortality from infection-related mortality was 2.5 (relative to 2.1), mortality from cardiac arrest was 1.3 (relative to 1.0), and mortality from myocardial infarction was 6.3 (relative to 4.4). Increased risk of adverse complications due to serum potassium imbalance after a2 day interval can be ameliorated by using proactive intervention provided by ICM 20, introduced by r.n. foley et al ,Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis,N.Engl.J.Med.365:1099-10,2011..

Although patients with ESRD are life-sustaining, HD and PD are never without substantial risk. There is a risk of over-and under-removal of critical blood components, including electrolytes, especially potassium. Following dialysis, subacute rebound of serum potassium occurs and these acute changes in serum potassium levels risk first altering the electrocardiogram and then causing severe arrhythmias. Furthermore, dialysis patients are still at significant risk of serum potassium imbalance during the dialysis interval period, as various factors, such as diet and potassium-lowering drugs, may affect the patient's serum potassium balance. The dialysis interval period is critical because potassium levels are not actively monitored and potentially fatal shifts above or below the safe range may be ignored and not resolved. Note that 7 days per week and that continuous and even daily dialysis is practically impossible, makes fluctuations in potassium balance a continuously existing reality.

Regardless of the dialysis interval, both forms of dialysis have the potential to disrupt the serum potassium balance of ESRD patients, as dialysis will remove potassium that has accumulated in the blood during the dialysis interval, and thus the risk of serum potassium production during or immediately after treatment may be too low or not low. The normal range of serum potassium in the general population is 3.5 to 5.0mEq/L, while the optimal potassium concentration range in HD patients is slightly higher. Recent studies have shown that patients with pre-dialysis serum potassium levels of 5.1mEq/L exhibit the lowest risk of Sudden Cardiac Death (SCD) in peridialysis, while serum potassium levels above and below 5.1mEqg/L are associated with increased risk due to equally fatal problems with hyperkalemia, as discussed in p.h.pun and J.P.Middleton,Dialysate Potassium,Dialysate Magnesium,and Hemodialysis Risk,J.Am.Soc.Nephrol.28:3441-3451,2017.

While pre-dialysis risks associated with serum potassium levels can generally be adjusted, the potential effects of potassium level reduction during and after dialysis treatment remain problematic. The potassium removal rate and the amount of potassium removed are largely a function of the potassium gradient of the serum potassium dialysate. A higher serum dialysate gradient results in a faster drop in serum potassium levels during treatment and a rapid rebound of potassium levels after dialysis when compared to a smaller serum dialysate gradient. Rapid decline and rebound of serum potassium results in acute changes in serum potassium levels, which in turn can cause hypokalemia or hyperkalemia, which can lead to palpitations, shortness of breath, chest pain, nausea, vomiting, or worse, conditions including stroke, dysrhythmias, myocardial infarction, and peri-dialysis SCD.

Hyperkalemia

In particular, sudden hyperkalemia or severe hyperkalemia is a life-threatening condition requiring immediate medical care, statistically indicating a link between abnormal serum potassium levels and death. Fig. 3 is a graph showing by way of example a relationship 40 between hyperkalemia 41 and chance of death 42. The x-axis 41 reflects the severity of Chronic Kidney Disease (CKD), progressing from stage 3 to stage 5 (i.e., ESRD), plus the control group labeled "none". The y-axis 42 reflects the mortality probability within one day of moderate and severe hyperkalemia events, respectively. One study found that patients with CKD were more likely to have hyperkalemia events at all stages of kidney disease than patients without CKD, with a greater 1-day mortality rate for hyperkalemia patients than normal blood events. Interestingly, as drawn by l.m. einhorn et al ,The Frequency of Hyperkalemia and Its Significance in Chronic Kidney Disease,Arch.Intern.Med.169(12):1156-1162 2009., hyperkalemia events in patients without CKD were instead associated with a higher 1-day mortality rate than hyperkalemia events in patients with CKD, with a negative correlation between the severity of CKD (per stages 43, 44, 45, 46) and the 1-day mortality rate resulting from hyperkalemia events, and with a higher mortality rate for more severe hyperkalemia. Patients with CKD sometimes moderately develop less defense mechanisms against higher potassium levels when repeatedly exposed to higher potassium levels than patients with secondary exposure to higher potassium levels. Nevertheless, this modest defensive response is extremely insufficient to offset the significant risk of hyperkalemia, regardless of the duration of exposure.

Correlation of ECG manifestations with serum Potassium imbalance

The onset or presence of hypokalemia and hyperkalemia during the dialysis and peridialysis phases can be detected by using ICM 20. ICM 20 is able to detect potassium imbalance and algorithmically trigger text, email, and telephone alerts to patients, families, doctors, and emergency medical services to varying degrees based on 24 hours/7 days/week/365 days/year (24/7/365) worldwide. The correlation between ECG changes, possibly but not always accompanied by the accompanying specific cardiac arrhythmias ("ECG manifestations"), and serum potassium imbalance, such as discussed in D.B. Diercks et al, electrocardiographic Manifestations: electrolyte Abnormalities, J.Emerg. Med.27:153-160 2004, is known and these characteristic ECG manifestations can be used to effectively trend in real-time diagnosis and treatment of hypokalemia and hyperkalemia by use of ICM 20. Fig. 4A-4E are graphs showing by way of example the relationship between Electrocardiographic (ECG) changes and serum potassium levels. The x-axis represents time and the y-axis represents electrical signal strength, typically in millivolts. Referring first to fig. 4A, an individual's ECG trace 50 is shown with normal serum potassium levels between 2.5-5.5mEq/L, with the ECG trace having three major components, P-wave, which represents depolarization of the atria, QRS complex, which represents depolarization of the ventricles, and T-wave, which represents repolarization of the ventricles. (note that the repolarization of the atrium is too small to see on the ECG and is hidden by the large amplitude QRS.)

Hypokalemia, which is an indication of hypokalemia, is associated with Ventricular Tachycardia (VT) and Ventricular Fibrillation (VF). Referring next to FIG. 4B, an ECG trace 55 of an individual having a serum potassium level below 2.5mEq/L and in a hypokalemia condition is shown. The ECG trace 55 has a depressed ST segment 56 and a prolonged QT interval 57 (or prolonged QTU interval), possibly with a distinct U-wave 58. Note that the U wave is not always visible in the patient's ECG, appears after the ventricular repolarized T wave, and may not always be observed due to its small size. Thus, there may be no significant U wave 58. That is, the U wave becomes very pronounced in the case of hypokalemia. These changes in ST segment and QTU intervals increase as hypokalemia becomes more severe, a trend being detectable by ICM. As serum potassium decreases, rapid death due to VT and VF becomes increasingly likely. The concomitant presence of ventricular arrhythmias was observed, in combination with low potassium levels detectable by ICM, added a higher level of urgency to the ascending intervention.

Hyperserum potassium, which is an indicator of hyperkalemia, is associated with bradycardia, heart block, asystole, and Congestive Heart Failure (CHF). Referring next to FIG. 4C, an ECG trace 60 of an individual with elevated serum potassium levels in the range of 7.0-8.0mEq/L is shown. The ECG trace 60 has a "peak" T wave 61, wherein the amplitude of the T wave increases gradually. Referring next to fig. 4D, at moderate potassium elevations in the range of 8.0-9.0mEq/L, ECG trace 65 has a widened QRS complex in addition to the specific peak T wave, plus a longer PR interval and a lower P wave amplitude. Finally, referring to FIG. 4E, there is the most severe hyperkalemia when potassium levels exceed 9.0mEq/L, and ECG trace 70 has a widened QRS complex and a widened T wave (which together resemble a "sine" wave without a P wave). Such events are predictive of death (in minutes). With a sustained rise in serum potassium, death due to asystole, myocardial paralysis and rhabdomyoparalysis becomes very probable.

ICM for identifying ECG performance

The risk of abnormal serum potassium causally related to HD or PD treatment is severe but can be greatly reduced and completely avoided by using ICM which, by monitoring patient ECG in real time, can identify, diagnose and trigger the treatment of hypokalemia and hyperkalemia by alerting appropriate individuals. The ICM wirelessly provides a continuous data stream of high quality ECG signals and incorporates an alarm when identifiable Electrocardiographic (ECG) changes and specific arrhythmias are detected, both of which together indicate the onset or presence of hypokalemia or hyperkalemia. The continuous data stream enables the ICM to operate without memory limitations. Fig. 5 is an external perspective view illustrating an Implantable Cardiac Monitor (ICM) 80 for maintaining potassium homeostasis according to one embodiment. The ICM 80 continuously captures the cardiac action potentials sensed by a pair of ECG sensing electrodes 82, 88 (or in another embodiment, three ECG sensing electrodes) as an ECG signal. In another embodiment, ICM 80 is combined with cloud-based diagnostics and monitoring, as discussed further below with reference to fig. 9.

The ECG signals form ECG traces that can be analyzed by ICM 80 in real time to identify the ECG changes described above, with or without arrhythmia for indicating hyperkalemia and hypokalemia. Desirably, the identification of an ECG change is indicative of the occurrence of an arrhythmia. In some cases they may occur simultaneously. If a medical condition is detected that is alarming, the data center and ICM 80 (if equipped with direct wireless communication) will contact the patient 11 and, if necessary, the medical care provider to take immediate intervention.

Based on 24/7/365, the ECG signal of the patient's heart is continuously monitored on a beat-by-beat basis. The ECG trace is evaluated by ICM 80 based on the beat-to-beat heartbeat and the unity of ECG and heart rhythm as it evolves over time. Each ECG trace represents real-time net electrical activity of the heart at a given moment and is evaluated beat-to-beat for a set of ECG performances. The ECG trace is stored as a set of data representing the heart rhythm and evaluated as a rhythm evolving over time for arrhythmia characteristics. ICM 80 captures the individual waveform components of each heartbeat and their characteristics (including their presence or absence, duration and amplitude). Furthermore, when capturing each heartbeat, ICM 80 is able to compare the heartbeats to identify any changes that may occur over time, for example, a gradual increase in T-wave amplitude will be detected along with timing the increase, which is notable because a rapidly evolving increase in T-wave amplitude is a key indicator of fatal hyperkalemia. By storing heartbeats, ICM 80 may also compare heartbeats observed over the entire two-day interval between heartbeats and dialysis sessions from an early recording period, i.e., for example, the occurrence of an increase in T-wave amplitude may indicate an offset toward hyperkalemia that, while not conforming to the clinical definition of potassium levels rising above 6.0mEq/L, may be sufficient to warrant physician interrogation and patient follow-up. Furthermore, the ability to identify beat-to-beat variations also enables ICM 80 to identify various possible arrhythmias. Thus, both beat-to-beat ECG changes and specific arrhythmias may be fully identified on a real-time, full-time basis by ICM 80.

Inapplicability of existing implantable devices

Notably, existing implantable cardiac monitoring devices have traditionally been used to detect arrhythmias by occasionally using algorithms based on a limited amount of binned data and stored data, such that cardiac activity is not tracked on a beat-to-beat basis. Instead, these devices digitize the ECG voltages and process them to identify specific arrhythmia patterns (primarily atrial fibrillation and ventricular tachycardia), but represent only an extremely small subset of the known and potentially fatal arrhythmia patterns.

More specifically, existing implantable cardiac monitoring devices do not capture characteristics of the various waveform artifacts that make up the ECG used to track potassium metabolism. Data critical to determining serum potassium homeostasis or its loss, such as the amplitude and polarity of the T wave or the presence or absence of the U wave, are not captured or even measured at all. Furthermore, these devices are unable to detect the same important beat-to-beat variations that may occur for these artifacts, such as gradual and abrupt increases in T-wave amplitude. Thus, existing implantable cardiac monitoring devices fail to identify ECG changes and, where applicable, specific arrhythmias indicative of hyperkalemia and hypokalemia, as described above. These types of monitoring devices are memory-constrained and are not constructed at all for continuous monitoring of trends in any critical parameter that is critical for detecting low or high serum potassium levels on a beat-to-beat basis. Instead, such devices focus on identifying arrhythmia episodes (episode) by relying on a form of loop recorder that is forced to continually re-record on early ECG observations to preserve memory, ECG traces being binned and averaged to generalized "episodes" to lose critical beat-to-beat (heartbeat) data. Since no beat-to-beat data is stored, it cannot be used for beat-to-beat comparison analysis of ECG features that are not associated with arrhythmias. This sporadic approach means that because these devices effectively seek "snapshots" of the ECG trace that match an arrhythmia pattern, such as Atrial Fibrillation (AF), the evolving changes in the patient's ECG over time as serum potassium levels fall or rise cannot be captured. Furthermore, when the device is focused on sporadic ECG monitoring, individual ECG artifacts (such as T-waves) have at most limited visibility, and the increase in T-wave amplitude required to identify the onset of hyperkalemia is not discernable.

Continuous real-time monitoring

ICM 80 is designed to be implanted in a living body and to operate over an extended period of time while potentially monitoring different types of patient physiology at different times and in different manners. The ICM 80 may record each heartbeat, perform a real-time transmission or delay a transmission, which may occur, for example, two days or more after recording or live monitoring. ICM 80 is equipped with ECG sensing electrodes 82, 88 and, in another embodiment, is equipped with one or more physiological sensors including, but not exhaustive, temperature, pulse oximeter, oxygen saturation, respiration, blood glucose, blood pressure, and drug levels or any suitable measure of medical condition or disease.

By using ICM 80, the significance of making long-term continuous ICM data viable is profound. Long-term disease management data facilitates home medical care and web-based medical practice, and continuous data of key physiological parameters will provide new insight into disease progression and management for all health conditions (not just those related to CKD). Thus, continuous ICM data will be available for medical decisions affecting a variety of chronic diseases, and drug, device and program management may be optimized to ensure optimal medical care over years of care. The long-term view provided by continuous ICM data will enable healthcare providers to begin grasping early signs of devastating disease through extensive population studies (which has heretofore been impossible).

When a change in the ECG is detected with a specific arrhythmia indicating the onset or presence of hypokalemia or hyperkalemia, ICM 80 generates an emergency trigger that is transmitted to a data center for immediate real-time action and patient follow-up as further described below with reference to fig. 10. In another embodiment, ICM 80 may alert the patient directly through a wireless access point or other wireless communication interface using a mobile phone or wirelessly connectable device, including a tablet or notebook or wired desktop.

In yet another embodiment, ICM 80 may also monitor non-physiological data, such as gestures derived from data measured by an actigraphy sensor, an accelerometer, or an inertial motion sensor, when equipped with an appropriate type of sensor. Other types of physiological and non-physiological data capture sensors and forms are also possible, such as cardiac input levels, thoracic impedance, and sound recordings (including supersonic recordings and subsonic recordings). In addition, medical history, diagnostic test reports, dialysate changes, surgery and treatment procedures may be entered into the ICM database as portable self-contained medical records.

ICM assembly

ICM 80 includes three main components. The main intermediate portion of ICM 80 is a central body 81, which may be formed of medical grade titanium or similar medical implant security material. The central body 81 has a tubular or cylindrical shape defining an axial bore providing a hollow tubular or cylindrical lumen extending longitudinally along the length of the central body 81 and opening at both end caps. Other shapes are possible, with non-circular, non-tubular or non-spherical shapes. Circular hemispherical end caps 82 and 83 are welded or otherwise secured to the center body 81 to form a hermetically sealed device housing. The end caps 82 and 83 may be formed in other shapes, such as tips or half tips.

ICM 80 is shaped for long-term comfortable permanent implantation into a subcutaneous site located axially in the parasternal region of the chest and slightly offset to the left or right of the midline of the sternum. This location is ideal for the type of cardiac ECG monitoring that emphasizes the propagation of low amplitude, relatively low frequency content cardiac action potentials (particularly P-waves generated during atrial and ventricular activation of atrial and ventricular repolarization), in contrast to existing implantable cardiac monitoring devices that are intended for short-term subcutaneous implantation into the left chest that sits diagonally relative to the heart.

The central body 81 houses a flexible circuit board, a low frequency resonant charging antenna to facilitate device charging, and an on-board power supply including a rechargeable energy battery, battery or super capacitor. ICM 80 needs to be charged only about once a month, with a charging time of about 10 minutes. One of the hemispherical end caps, referred to as the "guard electrode" 82, serves the dual purpose of acting as an electrode as well as housing the patient and device guard components. The other hemispherical end cap, called a "radar dome" 83, houses a high frequency antenna for transmitting data over an RF link, for example using bluetooth or WiFi. In addition, a "radar dome" 83 may be used to house the sensing antenna and sensing link. The RF link may also be used for device calibration and configuration. In another embodiment, the "radar dome" 83 may also house physiological sensors, such as pulse oximeters and blood pressure meters. In yet another embodiment, an optically transparent "radar dome" 83 may allow light or other forms of radiation to be received and transmitted therefrom to passively facilitate collection of other vital signs, such as pulse oximetry and blood pressure. In yet another embodiment, an optical fiber or lens implanted in the "radar dome" 83 may facilitate collection of vital signs by sensors housed elsewhere within the ICM 80.

In one embodiment, ICM 80 has a total length of about 5.5cm to about 8.5cm, with an outer diameter of about 5-8mm and a wall thickness of about 0.3mm measured on central body 81, however, other dimensions (including total length, wall thickness, and outer diameter) are possible depending on the type and number of electronic circuitry and power supplies and physiological and non-physiological sensors that need to be housed therein.

In another embodiment, ICM 80 may be filled with a gas, such as argon or other inert gas. In particular, argon is typically used when welding titanium components, and also serves to protect the electrical components and promote device life when oxygen to be purged is blown into the interior of ICM 80. In addition, a support structure, such as an acrylic rod, may be used as an internal spacer to help hold the internal components in place.

In one embodiment, the center body 81 and the "guard electrode" 82 may be bead blasted to increase the roughness of the center body 81 to improve silicone or parylene bonding, respectively, and to increase the surface area of the "guard electrode" 82 for better signal quality. Titanium nitride coatings may also be applied to significantly increase the surface area of the device.

The conductive surface 88 is formed by partially insulating the outer surface of the center body 81 using a non-conductive insulating surface treatment or coating ("insulating coating") 89. An insulating coating 89 is typically applied to the outer surface nearest the "guard electrode" 82, which maximizes the electrode dipole spacing. In one embodiment, the insulating coating 89 may be a chemical vapor deposited multipolymer such as parylene C. In another embodiment, the insulating coating 89 may be a silicone polymer-based (polysiloxane) coating. Alternatively, two forms of coating may be employed, namely a multipolymer and a silicone polymer. The multipolymer exhibits excellent moisture resistance and insulation, but is susceptible to damage from scratches and gouges. The silicone polymer coating forms a durable protective layer and, when applied to a multi-polymer coating (such as parylene C), can protect the underlying coating from scratches and gouges when ICM 80 is inserted, repositioned, or removed.

The end 22 of the central body 81 closest to the conductive surface 88 interfaces with a "radar dome" 83. In one embodiment, the high frequency antenna is a discrete component contained within the "radar dome" 83. The high frequency antenna may be held in place by filling the cavity of the "radar dome" 83 with a filler material (such as acrylic, urethane, glass, or the like), and the high frequency antenna may be interfaced to the flexible circuit board via the electrical contacts 20, and the electrical contacts 20 may be soldered or bonded to the high frequency antenna. In another embodiment, the high frequency antenna is formed on a foldable "ear" portion of the flexible circuit board and routed into a "radar dome" 83 assembly.

In one embodiment, the "guard electrode" 82 and the exposed conductive surface 88 of the central body 81 act as an electrode dipole when configured to measure electrocardiographic signals. Other forms of electrode dipoles are also possible. The end cap 84 of the "guard electrode" 82 forms an electrode. The exposed conductive surface 88 of the central body 81 distal to the "guard electrode" 82 forms another distal electrode 90. The metal housing of the power supply provides an electrical feedthrough from the "guard electrode" 82 to the flexible circuit board, thereby simplifying the structure.

In another embodiment, a third electrode 91 is provided on ICM 80 as an additional exposed conductive surface on center body 81. The third electrode 91 allows additional electrode dipole pairs to be configured, including pairs comprising "guard electrode" 82 and distal electrode 90, "guard electrode d"82 and third electrode 91, and distal electrode 90 and third electrode 91. The multiple electrode dipoles enhance the ability of ICM 80 to discriminate the propagation of low-amplitude, relatively low frequency content cardiac action potentials, particularly P-waves generated during atrial and ventricular activation of atrial and ventricular repolarization. In still other embodiments, ICM 80 may have more than three electrodes.

Informally, the nonconductive hemispherical end caps form a "radar dome" (radar dome) 83 that serves as a housing for the high frequency antenna for RF data exchange. A high-frequency antenna for data exchange is accommodated in the "radar dome" 83. Note that more than one high frequency antenna may be included. The "radar dome" 83 is an assembly that includes an electrically insulating hemisphere 87 formed from a medical implant security grade material (such as acrylic, glass, dark red crystal or ceramic) and a metal weld ring formed from medical grade titanium or similar medical implant security metals. These parts are bonded together using press fit, brazing, laser welding or electron beam welding. In another embodiment, the high frequency antenna is defined as a part of a flexible circuit board or folded metal shape, fold line or other similar structure.

Informally, the conductive hemispherical end cap forms a "guard electrode" (feeder electrode) 82 that serves the dual purpose of an electrode as well as for housing patient and device guard components. The "guard electrode" 82 is an assembly that includes a conductive hemisphere 84 formed from medical grade titanium or similar medical implant safety conductor, an insulating ring 85 formed from medical implant safety material (such as acrylic, glass, dark red crystal or ceramic), and a metal weld ring 86, which metal weld ring 86 may include a chamfered edge to facilitate welding to a center body 81 formed from medical grade titanium or similar medical implant safety metal. These parts are bonded together by heat fitting, crimping, soldering, epoxy adhesive, silicone adhesive or other similar bonding agent.

In some cases, the proximity of the high frequency antenna to the conductive surface 88 exposed on the outer surface of the tubular body 81 may pose a risk of degradation of the ECG signal. Fig. 6 is an external perspective view showing ICM 100 for maintaining potassium homeostasis according to another embodiment. The electrode 101 formed as part of the "guard electrode" segment of the ICM 100 and the electrode 102 formed on the outer surface of the tubular body 81 are formed with scalloped cuts in their respective inward facing aspects. The electrode configuration minimizes potential parasitic coupling of electrodes 101 and 102 to the ground strap for the high frequency antenna loop. In addition, the shape of the electrode 101 of the "guard electrode" improves the performance and durability of the ceramic-titanium weld joint that connects the "guard electrode" 84 to the tubular body 81 when in use.

Microarchitecture

The operation of ICM 80, including data capture, analysis, and communication, is controlled by a programmable microcontroller. Fig. 7 is a block diagram illustrating the microarchitecture of ICM 80 of fig. 5. The microcontroller is remotely interfaced through a wireless Radio Frequency (RF) data communication link using a high frequency antenna housed within a "guard electrode" 84, which enables ICM 80 to provide continuous beat-to-beat monitoring and to be remotely reconfigured or reprogrammed to utilize one or more physiological sensors.

In one embodiment, a low power consumption, high efficiency microcontroller 111 may be used, such as a microcontroller from the RL78 series of microcontrollers provided by tokyo-rapa electronics, japan. Architecturally, microcontrollers are built around a Harvard architecture that physically separates the signal and storage paths for instruction and data storage. The microcontroller runs under a dedicated microprogram that is stored as firmware (rather than a general purpose operating system) as microcode in a non-volatile storage device, which helps to run efficiently and extend power life, but in another embodiment an operating system that includes a real-time operating system may be used. Note that memory is placed both above and outside the microcontroller and program instructions are expected to be stored in the flash memory of the microcontroller. The use of programmable firmware means that ICM 80 is not dependent on-board algorithms and can be field upgraded with enhanced functionality.

Microcontroller 111 interfaces with both the integrated and off-chip components that provide continuous and scalable monitoring capabilities for ICM 80. The voltage regulation/charge control circuit 118 interfaces with the low frequency resonant charge antenna 117 and the microcontroller 111, which together regulate and control the charging of the power supply 119. An integrated bluetooth system on a chip (SoC) transceiver circuit 112 interfaces similarly with high frequency antenna 34 and microcontroller 111 to provide data communication capabilities to ICM 80. The electrode dipoles are formed by electrodes 115 and 116, which electrodes 115 and 116 interface with an Analog Front End (AFE) 114 and a microcontroller 111 to enable electrocardiographic monitoring. In one embodiment, temperature, body motion recorder and motion sensing are provided by temperature sensor 120, hall effect switch 121 and accelerometer 122, respectively. Finally, the monitoring data containing the continuous ECG data waiting to be downloaded is stored in the mass memory 123 in the form of random access memory or other volatile or non-volatile memory means.

Other possible signs of ICM

ICM 80 implements a configurable hardware platform based on a reprogrammable microcontroller. ICM 80 is not dependent on-board algorithms and may be field upgraded with enhanced functionality. In one embodiment, the microcontroller is programmed with an uploadable firmware capable of identifying in real-time ECG manifestations indicative of underlying hypokalemia and hyperkalemia, as described above with reference to fig. 4B-4E, and upon identifying such ECG manifestations indicative of particular arrhythmias of hypokalemia and hyperkalemia onset or presence, ICM 80 generates an emergency trigger that is transmitted to a data center for immediate real-time action and patient follow-up, as further described below with reference to fig. 10.

The microcontroller-based design also provides flexibility in selecting the signal filtering and processing algorithm options appropriate for each patient. This microarchitecture allows for an optimal patient experience by eliminating designs that employ a cut-away approach and are dominant in considering accommodating the most difficult cases. The microarchitecture further accommodates changes in patient morphology, modifications to the filtering software can be dynamically selected and updated in the field as configuration updates pushed by the physician from the "cloud" (i.e., a server-side function virtualized as a server paradigm of widely available services through access to the internet or other wide area data communication network).

In another embodiment, transceiver 112 may be used in conjunction with a microcontroller to communicate with an ingestible sensor, such as that provided by protein DIGITAL HEALTH, inc (radwood city, california). The ingestible sensor is a pellet made of a biocompatible material that combines remotely monitored microelectronics with a drug or inert material that can be safely administered by a patient. Typically, the ingestible sensor is activated by gastric fluid dissolving or acting on its surface, after which the sensor begins to measure gastrointestinal physiology, and possibly other types of physiology. Ingestible sensors capable of communicating wirelessly, such as via bluetooth, medradio, or via WiFi, may be used as a real-time functional replacement in place of those that store recorded physiological information on-board the device. Such wireless-enabled ingestible sensors allow for the capture of sensory data in real-time. Furthermore, these types of ingestible sensors may be coupled with the ICM 80, and thus, may monitor patient drug compliance by providing accurate, time-dependent data that may be used to evaluate non-compliance and provide positive reinforcement. The patient's caregivers may be notified in real-time about the patient's behavior in terms of adhering to prescribed medications.

The described platform facilitates monitoring each heartbeat as compared to conventional non-rechargeable platforms that do not have sufficient power to store and transmit each heartbeat. In addition to monitoring each heartbeat, since the heartbeat may be downloaded (offload), the heartbeat may be suitably analyzed by intelligent algorithms that are not located in the ICM 80, which allows for better identification of arrhythmias and disease conditions than would otherwise be obtained using the computing resources of the ICM 80 alone, as the complexity of the algorithms is not limited by the processing, memory, storage, power and other resources available to the analysis device.

The microcontroller may be supplemented with additional physiological sensors including SpO ₂ sensors, blood pressure sensors, temperature sensors, respiratory rate sensors, glucose sensors, airflow sensors, and volumetric pressure sensors, as well as non-physiological sensors including accelerometers and inertial motion sensors. By the microcontroller 111, the sensor can be selectively activated over the implant lifetime, either in real-time or during reprogramming, to tailor patient monitoring to the continued diagnostic needs. These additional sensors may be effective in managing other disease conditions and helping doctors address a range of problems including, preferentially treating kidney transplants in stage 4 CKD patients with potassium problems, helping to protect stage 3-4 CKD patients, managing hyperkalemia in new york heart disease association (HYHA) stage 3-4 CHF patients who are using inhibitors of the renin-angiotensin-aldosterone system, managing hypokalemia in NYHA 1-4 CHF patients and hypertensive patients (i.e., patients who are using diuretics), and using thermometers (i.e., temperature monitoring in ICM, which is provided as an in-built diagnostic tool in connection with battery charging) for infectious, oncological, and chronic pulmonary diseases, and the like.

Method for identifying ECG performance

The ICM 80 continuously monitors the heart rate of the patient on a beat-to-beat basis, and in another embodiment, monitors physiological and other non-physiological metrics of the patient, depending on the sensors with which the ICM 80 is equipped. Fig. 8 is a flowchart illustrating a method 130 for continuously monitoring an electrocardiogram for use with the ICM 80 of fig. 5. Initially, after successful implantation, the microcontroller 111 performs a power-up sequence (step 131). During the power up sequence, the voltage of the power supply 119 is checked, the state of the mass memory (flash) 123 is confirmed (both in terms of operability check and available capacity), and the microcontroller operation is confirmed diagnostically.

Continuous real-time ECG monitoring

After the power-up sequence is satisfactorily completed, microcontroller 111 continues to execute a set of iterative processing loops (steps 132-146). Each processing cycle is performed simultaneously. The first processing cycle deals with continuous real-time monitoring of the ECG signal and, where applicable, with other data as well. During each iteration of this first processing cycle, the AFE 114 continuously senses the electrocardiographic signal through the electrode dipole created by the sensing electrodes 82, 88 (step 133), and furthermore, samples the patient physiological and non-physiological metrics at appropriate intervals, as applicable, depending on the sampling frequency selected for the particular type of data sensed. One or more physiological functions may be sensed at any given time. The type and sampling rate of the physiological functions are selectively activated by program control via the microcontroller 111 throughout the life cycle of the ICM 80, which in turn determines the hardware device used. For example, reading the patient's body temperature once per minute would require activating the temperature sensor 120. Non-physiological data, such as position or posture, is sensed in a similar manner, mutatis mutandis.

By sampling the AFE 114 and appropriate physiological function sensing hardware, the microcontroller 111 reads samples of the ECG signal and reads physiological functions and other data at appropriate intervals (step 134). Any ECG manifestations in the sensed ECG signals forming the ECG trace are identified, which may be indicative of the onset or presence of hypokalemia or hyperkalemia (step 135), as discussed further below with reference to fig. 9. Additional types of identification and evaluation of medical diagnostic artifacts may also be performed.

Each of the sampled ECG and physiological signals (in quantized and digitized form) is temporarily segmented in a buffer (step 136) for compression preparation for storage in mass memory 123 (step 137). After compression, the compressed ECG digitized samples are buffered again (step 138) and then written to mass storage 123 using the communication bus (step 139). Processing continues (step 146) and terminates only when ICM 80 is disabled or depleted of power. Still other operations and steps may be performed.

Alert and data download

The second processing cycle deals with the continuous real-time processing of the ECG signal and, if applicable, with other data. ICM 80 generates alerts and downloads stored monitoring data to a data center or other external device. Whenever any ECG manifestation in the sensed ECG signal, which may indicate the onset or presence of hypokalemia or hyperkalemia, is identified, the time as well as the type of dialysis is critical to the type of alert to be performed, and thus the timeliness of the occurrence of the ECG manifestation is evaluated (step 140), as further described below with reference to fig. 9. Other considerations may also be an element of the temporal assessment, in addition to or instead of timing and type of dialysis.

Based on the assessment of the severity and timing of the occurrence of hypokalemia or hyperkalemia, if this occurrence is deemed urgent (step 141), the doctor and his staff (for clarity and convenience, the expression "his" will be used herein, but should be understood as being a single vision for both sexes) is notified using, for example, a cell phone, a cellular enabled tablet, a network connected notebook or desktop computer, or other portable or stationary computing device executing a software application (step 142). ICM 80 may contact doctors and his staff directly through wireless communication or indirectly through a data center. Furthermore, if this occurrence is considered severe (step 143), such as in the case where fatal hyperkalemia has progressed, the patient participates directly on his own using, for example, a bedside monitor executing a software application, a cell phone, a cellular enabled tablet, a network-connected notebook or desktop computer, or other portable or stationary computing device. ICM 80 may contact the patient directly through wireless communication or indirectly through a data center. In extremely severe cases, especially when death due to cardiovascular causes is imminent, emergency medical services may also be used to automatically dispatch medical assistance to patients.

Finally, as part of this processing cycle, data is downloaded from ICM 80 (step 145). To download the stored data from mass storage, the ICM 80 is typically connected to the bedside monitor using bluetooth or other form of short range wireless communication and transmits the stored samples from mass storage 123 to the bedside monitor. Alternatively, ICM 80 may be connected to a computing device executing a software application to communicate with ICM 80, such as a cell phone, cellular enabled tablet, network-connected notebook or desktop computer, or other portable or stationary computing device, or may be connected directly to the data center itself. Further, the bedside monitor or other device relays the uploaded ECG and physiological function samples to the data center. After completion of the data download, the ICM 80 may or may not be disconnected from the bedside monitor depending on the ECG results. Processing continues (step 144) and terminates only when ICM 80 is disabled or depleted of power. Still other operations and steps may be performed.

ECG performance identification

As described above with reference to fig. 4B-4E, identifiable ECG changes and specific arrhythmias for indicating the onset or presence of hypokalemia or hyperkalemia are known and can be identified in real-time using ICM 80. FIG. 9 is a flow chart showing a procedure for identifying an ECG representation in an ECG signal for use in the method of FIG. 8. Although described with reference to an ECG signal sensed using ICM 80, other types of cutaneous and subcutaneous cardiac and physiological monitoring devices may be used provided that sufficient signal fidelity is available to distinguish the propagation of low-amplitude, relatively low-frequency content cardiac action potentials (particularly P-waves generated during atrial and ventricular activation atrial and ventricular repolarization).

At high levels, ICM 80 can detect high and low serum potassium in real time by:

1) QT interval or QTU interval is measured continuously with or without VT for low potassium.

2) The T-wave amplitude for high potassium was measured continuously.

3) The broadening of QRS intervals for high potassium is measured continuously.

4) The ECG metrics described above are tracked and correlated with any episodes or frequency variations of all arrhythmias (particularly VT and bradycardia).

Other methods are also possible in addition to or instead of the above methods. Details of the ECG performance identification performed by ICM 80 will now be discussed in detail.

First, the onset or presence of hypokalemia is assessed. Hypokalemia, in which the potassium content is below 2.5mEq/L, is marked based on its ECG characteristics (step 151), which include a depressed ST segment 56 and QT interval prolongation 57 (or QTU intervals), possibly accompanied by a distinct U-wave 58 (step 152). Hypokalemia is usually caused by dialysis, diuretics and CHF drugs, and can be alleviated by ICM 80 to increase the alert as QT interval increases, and by the physician changing dialysate concentration and administering potassium supplements during dialysis.

The onset or presence of hyperkalemia is then assessed. Note that the order of evaluation of hypokalemia and hyperkalemia is interchangeable. Evaluation begins with consideration of the onset of hyperkalemia. Hyperkalemia, in which potassium is greater than 6.0mEq/L, is marked based on early ECG features (step 153), including peak T-waves 61, with P-wave broadening or flattening and P-R interval lengthening (step 154).

As serum potassium levels rise, ECG performance becomes more pronounced as hyperkalemia progresses from early to moderate severity. ICM 80 detects sustained changes in ECG trace 50 by identifying both ongoing ECG changes and the occurrence of a particular arrhythmia pattern. As potassium rises, hyperkalemia where potassium is greater than 7.0mEq/L is marked based on mid-term ECG features including QRS complex broadening, peak T-waves, longer PR intervals, and lower P-waves (step 156). These ECG manifestations are associated with specific arrhythmias including sinus bradycardia, atrioventricular block, slow junctional or ventricular escape rhythms, and slower AF.

Finally, it is well known that, depending on high or low potassium levels and any underlying heart disease that is susceptible to such potassium abnormalities, a narrow range of potassium deviations above safe potassium levels are potentially fatal to ESRD patients over days, hours, and even minutes. Thus, ICM 80 continues to detect progressive hyperkalemia when early or mid-term ECG features have been identified and marks hyperkalemia where potassium is greater than 9.0mEq/L based on ECG features that indicate impending fatal hyperkalemia including a QRS complex similar to a "sine" wave without a P wave and a developmental wave of a T wave, i.e., a pre-death rhythm (step 157). ECG features may include Pulseless Electrical Activity (PEA) with a singular, broad-wave group rhythm. These ECG manifestations are associated with specific arrhythmias including asystole, slow VF and eventual patient death.

Emergency notification

The timing of a dialysis session is related to the identification of an ECG performance that may indicate the onset or presence of hypokalemia or hyperkalemia, which is critical for determining the urgency of medical assistance. Patients with ESRD may develop dangerously low or high potassium levels in a short period of time. FIG. 10 is a flow chart showing a procedure for evaluating timeliness of an ECG performance used in the method of FIG. 8. As identified by the ICM 80 via ECG traces, the timeliness of the dialysis is considered as a factor to determine the urgency of hypokalemia and hyperkalemia. Furthermore, taking the type of dialysis (whether HD or PD) as a factor is taken into account in the form of medical assistance provided, as HD patients are more often visiting doctors and their staff at any time during the dialysis and peri-dialysis periods, while PD patients may be at home and may fall asleep during the dialysis session. In another embodiment, the medical devices used to perform HD and PD dialysis are interfaced with the data center and, if suitably configured for direct wireless communication, with the ICM 80, so that the data center personnel (and ICM 80) are aware of the start and stop of dialysis, which will enable the notification to better accommodate the patient's real-time situation (especially for the dialysis session and the peri-dialysis session).

At a higher level, once the crossing of the preset threshold occurs, a notification is sent to the doctor and his patient by various methods, including telephone calls, sms, email or EMS dispatch:

1) For low potassium, an early alert is generated once an increase in QT interval is detected (with or without abrupt VT).

2) For high potassium, an early warning is generated once an increase in T-wave amplitude is detected.

3) For high potassium, an emergency alert is generated once an increase in QRS interval width is detected.

4) For high potassium, an emergency notification is generated once a significant increase in QRS interval width (with or without concomitant heart block and significant bradycardia occurrence) is detected.

5) For high potassium or low potassium, an emergency notification is generated once a long VT trace of over 20 or over 180bpm and a heart rate pause of over 5 seconds (regardless of the extent of ECG variation) are detected.

Other thresholds are also possible in addition to or instead of the above-described thresholds.

When notified, a doctor or medical care provider may apply interventions including:

1) The potassium supplement is used directly for low potassium or the potassium absorber is used directly for high potassium.

2) The dialysate concentration or type is increased or decreased as indicated by the ECG, for example, increasing or decreasing glucose concentration, or switching from glucose to icodextrin.

3) Changing the dialysate schedule and considering dynamic scheduling based on ECG data.

4) Prompting a doctor or healthcare provider to make a medical call, scheduling an ER visit, or dispatching an Emergency Medical Service (EMS) as directed by the severity of the ECG data.

Other interventions may also be performed.

The data center securely maintains patient medical information in Electronic Medical Records (EMRs) that are used as historic and persistent resources for medical diagnosis, prognosis, and treatment. Each EMR may include specific details regarding the type of dialysis treatment being performed, including the type of dialysate and other drugs used or administered, their amounts, concentrations or dosages, and timing and frequency. These specific details may be considered as factors in the specific advice of medical staff.

Importantly, the data center and ICM 80 can advantageously utilize the patient's EMR to quickly make a historical review of the patient's medical history to identify early events involving hypokalemia or hyperkalemia, cardiac arrhythmias, or any other medical problem, and can automatically make medical diagnoses, if applicable, or generate advice that can be provided to a doctor, his staff, the patient, or his caregivers. As an example, when the patient recovers from HD, his T wave may start to rise. Knowing that he had previously suffered from an increase in T-wave amplitude and then became a VT complication has important implications for how the doctor would provide care in the current event. This ability to access, process and factor the patient's complete medical history (implemented as EMR), particularly those related to dialysis treatment and serum potassium homeostasis, can be critical to ensure proper patient care because external factors, such as the patient being traveling and caring at a dialysis center away from home, can cause the existing healthcare provider to lose the necessary information, which can lead to a distinct outcome, i.e., an aggressive solution or patient sad news (of someone's death). Details of physician and patient notification will now be discussed in detail.

Hyperkalemia can occur in a short period of time, usually after dialysis, and has a variety of common causes. Factors are known to the patient, such as delaying entry into a dialysis session, rescheduling the dialysis session time, or experiencing under-dialysis due to shortened treatment time or complications in fistula entry. Other factors may be less pronounced for patients, including diseases or acute health conditions where infection is sudden but invasive. Such diseases include infection COVID-19, influenza or other infections, even minor infections. Acute health conditions include lower gastrointestinal discomfort leading to diarrhea. Each of these examples COVID-19, influenza, and lower gastrointestinal discomfort can lead to dehydration of the patient, resulting in elevated potassium levels.

Ideally, any acute health condition affecting the patient's health should be informed to his doctor. Thus, the patient will typically record his acute health condition using a bedside monitor (described further below with reference to fig. 11) or a mobile device (such as a cell phone, tablet, etc.) when possible. Further, the bedside monitor or mobile device will connect with the data center and alert the patient's physician to the acute health condition. In cases where the condition is known to have an effect on potassium levels, such as in patients with COVID-19, influenza and reports of lower gastrointestinal distress, the ICM and data center may automatically take action on the acute health condition (step 171) by increasing the urgency of seeking medical assistance (step 172), or the doctor or its staff may increase the urgency of seeking medical assistance after reviewing the acute medical condition and any related factors. If acute conditions occur with alarming rapidity through the data available to the ICM (including ECG), the urgency of seeking medical assistance will also automatically increase, as severe episodes of diarrhea therein will rapidly dehydrate the patient, raise potassium levels and rapidly raise T-wave amplitudes.

During the dialysis interval, the patient undergoing dialysis is typically left unattended medically and is therefore at significant risk of suffering from adverse consequences, as their hypokalemia or hyperkalemia is typically not found and resolved. The two-day interval between dialysis sessions is extremely critical and sometimes fatal to the ESRD patient undergoing dialysis (step 173). In practice, "two days" may be misleading. Generally, the two-day interval is from the end of the friday dialysis treatment to the beginning of the monday dialysis treatment. The amount of time between the start and end of dialysis may actually exceed two days, for example, a patient completing dialysis in friday noon may be scheduled to begin dialysis at 6 pm on monday, which is a 78 hour pause. During the course of one week, the patient's dialysis session may be as long as 36 hours, with a 78 hour pause in this example being more than twice as long as he spends between monday to wednesday and friday to friday dialysis sessions, so his serum potassium imbalance may be severe and even fatal. In order to help address the serious problems associated with the two-day interval (as discussed in detail above with reference to fig. 2, statistically high mortality rates of dialysis patients after the two-day interval are highlighted), special attention is paid to monitoring potassium levels during the two-day interval. In the event that low or high serum potassium levels are identified during the two day interval, the urgency of seeking medical assistance is increased (step 174), which may be achieved by notifying the physician and his staff, particularly the patient undergoing HD, and notifying the patient who should seek medical assistance. In the case of a patient undergoing PD, his partner may be notified, such as a spouse or other individual who is typically at home with the patient. The severity and rapidity of onset of hypokalemia or hyperkalemia can highlight the urgency of the notification, and if the patient's condition rapidly worsens, medical assistance can be immediately dispatched to the patient if necessary. The one-day interval between dialysis sessions remains very critical for the ESRD patient undergoing dialysis (step 175), but due to the shorter period of time, the degree of urgency to seek medical assistance (step 176) may be less, and the urgency of concern may be reduced, as the patient will be under medical supervision the next day if he is undergoing HD.

Because of the presence of trained medical personnel, the risk of patients undergoing HD during the dialysis and peri-dialysis periods may be minimal, but HD patients are at risk during longer dialysis intervals. However, the risk of PD patients during these same periods is always high, especially if PD patients are subject to dialysis during home sleep and may take weeks or even longer before receiving medical attention. The ICM 80 continuously monitors ECG signals whether the patient is HD or PD and analyzes these ECG manifestations and accompanying arrhythmias for indications of hypokalemia and hyperkalemia. In another embodiment, if the device for performing dialysis is equipped with direct wireless communication and the exact start and stop of dialysis is known and taken into account in the notification process, the device for performing dialysis is communicatively interfaced with the data center and possibly with the ICM 80. Otherwise, the medical personnel, patient, or their caregivers may need to tell the data center (or ICM 80) when to begin and end dialysis.

During the dialysis interval period (step 177), the medical personnel, and possibly the patient, are notified of the potassium imbalance, which for patients undergoing HD, the medical personnel can address by possibly adjusting the dialysate concentration and administering a potassium supplement or an ongoing dialysis treatment (step 178). In another embodiment, the notification may include specific advice regarding changes in dialysate concentration and drug dosage based on stored details maintained in the patient's EMR, rather than waiting for intervention by the attending physician or nurse.

For a patient who is doing PD, the patient is required to contact his doctor or medical care provider for assistance, and if the patient is not taking his body due to, for example, sleeping, the patient's caregivers may be contacted instead. During the peridialysis period (or pre-dialysis and recovery periods) (step 179), medical personnel or patients are notified of the potassium imbalance and appropriate remedial steps are taken (step 180). Although blood draws are typically performed prior to the beginning of an HD session, post-dialysis serum potassium levels are typically not measured, and the ICM 80 provides an alert to medical personnel and patients that the benefit is to be able to immediately resolve the potassium imbalance before the condition worsens. Still other temporal considerations may be made.

Patient workflow

ICM 80 is useful for identifying and diagnosing hypokalemia and hyperkalemia and providing appropriate medical advice or attention if necessary. ICM 80 works in conjunction with a data center or other cloud-based computing infrastructure to interact with the patient or its caregivers, medical personnel, and EMS as necessary.

A real-time and proactive approach for diagnosing and addressing serum potassium imbalance begins with providing an ICM 192 to a patient, such as described above with reference to fig. 5. Other forms of ECG monitors (whether implantable or dermatological) may also be used provided that adequate signal fidelity is available. Fig. 9 is a flow chart illustrating a patient workflow 190. Initially, doctor 191 implants ICM 80 into patient 11 (step 192). To optimize monitoring of cardiac electrocardiography (where low amplitude, relatively low frequency content is focused on propagation of cardiac action potentials, particularly P-waves generated during atrial and ventricular activation of atrial and ventricular repolarization), ICM 192 is preferably implanted in a subcutaneous site located axially and slightly to the left or right of the sternal midline in the parasternal region of the chest. Subcutaneous implantation may be performed as an outpatient procedure, such as at a doctor's office, using specialized implantation instruments including a trocar to cut the skin and form a subcutaneous tunnel, and a cannula through which ICM 192 may be guided into place, and then the implantation instrument withdrawn and the surgical incision closed. Other implantation sites within the body are also possible, depending at least in part on the desired physiological range to be monitored.

The patient 11 returns to home 193 and is equipped with a bedside monitor and ICM charging station (step 194). Alternatively, instead of a bedside monitor, the ICM 80 may be connected to a computing device, such as a cell phone, a cellular enabled tablet, a network-connected notebook or desktop computer, or other portable or stationary computing device, capable of executing software applications to communicate with the ICM 80. For example, in response to ICM 80 identifying ECG changes and specific arrhythmias for indicating the onset or presence of hypokalemia or hyperkalemia, a bedside monitor or other device provides patient 11 with access to immediate care via automatic data transmission and generated alerts. The bedside monitor and charging station also allows the ICM 192 to download stored monitoring data for relay to a data center or other external device and recharge the on-board power supply approximately once a month (step 195). The bedside monitor may also be used to download new programming to the ICM 192. The data center saves the uploaded monitoring data, including continuous ECG and physiological data, to the patient's Electronic Medical Record (EMR). Finally, the patient records the symptoms as a diary using a software application executed by a cell phone or computer, as needed (step 196).

Doctor and staff workflow

After the patient 11's curtain, the doctor and his staff members participate in supporting the workflow to ensure that the patient 11 is able to maintain serum potassium homeostasis. Fig. 10 is a flow chart showing doctor 191 and staff member workflow 200. Based on the patient's EMR maintained by the data center, the doctor 191 and staff members receive daily or periodic notifications of patient events and monthly summary reports (step 201). Notifications and reports are generated by the data center based on the uploaded ECG and physiological function samples sent by ICM 80, the patient EMR portal can be expanded to accommodate other medical records, test results, and patient medical history, and to allow for easy, long-term review and comparison by doctor 191. Thus, the physician 191 can view the entire ECG and other patient data and navigate through the data to any previous time period (step 202). Typically, the staff will be responsible for the task of the department of billing and insurance reimbursement for the patient. Accordingly, the staff bills the patient or insurer for the implantation procedure (step 203) and monthly for the summary report generated (step 204).

The real-time and proactive diagnosis and resolution of serum potassium imbalance is provided as a special sub-example of doctor 191 and staff workflow 200. If ICM 80 triggered the occurrence of an emergency event indicating hyperkalemia or hypokalemia, doctor 191 and the staff member may receive an emergency notification generated by the data center (step 205). In another embodiment, the data center generates an emergency event indicating hyperkalemia or hypokalemia based on the download data received from ICM 80.

Receiving an emergency notification may trigger two parallel tasks. First, doctor 191 and staff members may establish immediate contact with patient 11 (step 206) to provide guidance, such as in the case of marking hypokalemia or hyperkalemia, or to provide remedial action to be taken, including instructions reported to the hospital, such as in the case of marking moderate hyperkalemia. Also, emergency care assistance may be dispatched directly to the patient 11 where appropriate, such as in the case of marking severe hyperkalemia (step 207). Other steps for identifying, diagnosing and treating hypokalemia and hyperkalemia are also possible, including relaying instructions to a dialysis center or to a bedside monitor or patient's mobile device where appropriate.

Example case study

To illustrate the above-described method of monitoring a patient's ECG in real-time with the aid of an ICM to identify, diagnose and trigger treatment of hypokalemia and hyperkalemia, an illustrative set of case studies will now be discussed. Fig. 13A-13C are schematic diagrams showing, by way of example, patient case studies 210, 220, 230 presented in tabular form, wherein events 211, 221, 231 are indicated by the table, with patient history 212, 222, 232, and 31 day summaries 213, 223, 233, and comments reflecting significant morbidity associated with patient condition. In each case study, the ICM wirelessly provides a continuous data stream of high quality ECG signals and incorporates alarms upon detection of identifiable ECG changes and specific arrhythmias indicative of hypokalemia or hyperkalemia onset or presence, and then appropriate remedial action is taken.

63 Year old female patient with dialysate change

Referring first to fig. 13A, an illustrative case study of a 63 year old female patient with PD is shown. The patient did not lose sufficient body weight due to water retention (edema). Approximately mid-month, her physician changes her dialysate to higher (concentration) glucose dialysate (214) to increase urination or remove water. However, the changes in the dialysate are too strong, resulting in excessive potassium removal, which in turn leads to a marked prolongation of QT interval due to hypokalemia. This change is then a strong, more dangerous VT incident.

The use of ICM enables her QT interval changes to be observed on a beat-to-beat basis. Furthermore, her frequency of VT incidences may be related to an increase in her QT interval, indicating a subsequent risk towards impending cardiac arrest and a potentially fatal trend. In this example, as her QT interval lengthens and the frequency of VT episodes begins to increase, her physician may be called based on an alert generated using the ICM (215). Further, as her heart rate continues to rise above 180bpm, the EMS is called again based on the alert generated by using the ICM (216).

73 Year old male patient with Heart Failure (HF) drug change

Referring next to fig. 13B, an illustrative case study of a 73 year old male patient with PD is shown. The patient suffers from heart failure and is taking medicine. Approximately mid-month, his doctor changed his heart failure medications, which resulted in an increase in his serum potassium levels. As potassium increases his T wave amplitude increases, followed by a broadening of his QRS interval. After a while, cardiac arrest develops.

Note that QT interval also shortens with increasing potassium levels, contrary to what is observed in hypokalemia. Typically, as potassium levels rise, the P wave rises first, followed by a broadening of the QRS interval. These changes are accompanied by sinus bradycardia with a pause of 5 to 10 seconds. When a succession of sinus bradycardia occurs and a pause of at least five seconds is detected, the EMS is called (224) based on an alarm generated by using the ICM.

63 Year old male patient with mild COVID-19

Referring finally to fig. 13C, an illustrative case study of a 63 year old male patient with PD is shown. About mid-month, the patient had stained with mild COVID-19 cases, which resulted in dehydration of the patient. Furthermore, his dehydration leads to elevated potassium levels with typical ECG changes and subsequent arrhythmia, as shown in previous case studies of heart failure patients.

Note that any dehydration cause may result in higher potassium levels, including COVID-19, influenza, anorexia, lower gastrointestinal discomfort, other infections, and fever. When it involves detecting the occurrence of sinus bradycardia, the EMS is called (234) based on an alert generated by using the ICM.

Still other examples are possible regarding monitoring the patient's ECG in real time with the aid of ICM to identify, diagnose and trigger the efficacy of hypokalemia and hyperkalemia.

While the invention has been particularly shown and described with reference to embodiments thereof, it will be understood by those skilled in the art that the foregoing and other changes in forms and details may be made therein without departing from the spirit and scope.

Claims (27)

1. A method for maintaining serum potassium homeostasis by subcutaneous monitoring, comprising the steps of:

Maintaining a set of ECG performances indicative of at least one of onset and presence of loss of serum potassium homeostasis in dialysis patients;

continuously subcutaneously monitoring an electrocardiogram, ECG, signal of the heart of the patient on a beat-by-beat basis;

Processing the ECG signal in real time into a set of ECG traces, wherein each ECG trace represents net electrical activity of the heart at a given moment;

evaluating each ECG trace for the set of ECG performances, and

An alert of a medical condition is generated when at least one of the ECG performances is identified in one or more of the ECG traces.

2. The method of claim 1, further comprising the step of maintaining an arrhythmia signature for further indicating at least one of the onset and presence of a loss of serum potassium homeostasis in the dialysis patient;

Evaluating the ECG trace over time for the arrhythmia characteristic, and

A medical condition alert is generated when at least one of the ECG performances is identified in one or more of the ECG traces and at least one of the arrhythmias is identified in the ECG trace over time.

3. The method of claim 1, further comprising the step of:

for hypokalemia, a set of ECG performances is defined, the set of ECG performances including one or more of a depressed ST segment and at least one of a prolonged QT interval and a prolonged QTU interval, and

The QT interval and the QTU interval in each ECG trace are monitored.

4. A method according to claim 3, further comprising the step of:

for hypokalemia, defining arrhythmia characteristics including ventricular tachycardia;

Evaluating the ECG trace over time for the arrhythmia characteristic, and

A medical condition alert is generated when at least one of the ECG performances is identified in one or more of the ECG traces and ventricular tachycardia is identified in the ECG trace over time.

5. The method of claim 1, further comprising the step of:

For early hyperkalemia, a set of ECG performances is defined, including those accompanied by P-waves

One or more of broadening or flattening peak T-waves and P-R interval extension, and

T-waves in each ECG trace are monitored.

6. A method according to claim 3, further comprising the step of:

For mid-term hyperkalemia, a set of ECG performances is defined, including one or more of QRS complex broadening, peak T-waves, longer PR intervals, and lower P-waves, and

QRS intervals in each ECG trace are monitored.

7. The method of claim 6, further comprising the step of:

For fatal hyperkalemia, a set of ECG performances including one or more of a QRS complex resembling a "sine" wave and a developmental wave of a T wave are defined, and

QRST intervals in each ECG trace are monitored.

8. The method of claim 7, further comprising the step of:

For the fatal hyperkalemia, defining a set of ECG performances including one or more of pre-death rhythms, pulseless electrical activity PEA, and broad-wave group rhythms, and

Evaluating the ECG trace over time for the arrhythmia, and

A medical condition alert is generated when at least one of the ECG performances is identified in one or more of the ECG traces and one or more of a pre-death rhythm, PEA, and broad-wave group rhythm is identified in the ECG trace over time.

9. The method of claim 7, further comprising the steps of further defining an ECG presentation containing pauses greater than 5 seconds, and

The EMS is scheduled when one or more substantially continuous pauses of greater than 5 seconds occur in one or more of the ECG traces.

10. The method of claim 1, further comprising the steps of receiving an indication of an acute medical condition afflicting the patient, and

Increasing the urgency of the alert.

11. The method of claim 10, wherein the acute medical condition comprises a health condition selected from the group consisting of COVID-19, influenza, anorexia, lower gastrointestinal discomfort, other infections, and fever.

12. The method of claim 1, further comprising the steps of maintaining a schedule of the dialysis, and

The urgency of the alarm is increased if the alarm occurs during a two-day interval between the dialysis sessions.

13. The method of claim 1, further comprising the steps of maintaining a schedule of the dialysis, and

If the alarm occurs during a dialysis interval of a dialysis session, one or more of medical personnel, the patient and a caregiver of the patient are immediately notified of a recommendation to adjust the dialysis treatment.

14. The method of claim 1, further comprising the step of communicatively interfacing with a device for performing the dialysis on the patient.

15. The method of claim 14, further comprising the step of maintaining an electronic medical record of the patient including details regarding the type of dialysis treatment being performed, the type and amount of dialysate being used, the concentration, the frequency and the dosage, one or more of other medications being used and the amount, concentration, frequency and dosage, and

Based on the type of dialysis treatment being performed and the medical condition behind the alarm, it is suggested to adjust one or more of the dialysate and other drugs.

16. The method of claim 1, further comprising the steps of maintaining a schedule of the dialysis, and

If the alarm occurs during the peri-dialysis period of a dialysis session, one or more of the medical personnel, the patient, and the patient care provider are immediately notified of advice for seeking medical assistance.

17. An implantable cardiac monitor for maintaining potassium homeostasis, comprising:

an implantable housing formed in a cylindrical shape having a rounded hemispherical end cap and comprising a biocompatible material suitable for implantation into a living body;

At least one pair of ECG sensing electrodes disposed on the ventral surface and on opposite ends of the implantable housing, operatively disposed about the end caps to facilitate the closest sensing of low amplitude, low frequency content cardiac action potentials generated during atrial and ventricular activation atrial and ventricular repolarization, and

An electronic circuit disposed within the housing assembly, comprising a low power microcontroller operable under the control of a modular micro-program, an ECG front end circuit interfaced with the microcontroller and configured to capture cardiac action potentials sensed by the pair of ECG sensing electrodes as an ECG signal, the ECG signal comprising a set of ECG traces, wherein each ECG trace represents net electrical activity of the heart at a given moment, firmware disposed as part of the micro-program, the micro-program comprising identifying ECG manifestations in one or more of the ECG traces based on beat-to-beat beats, and a non-volatile memory electrically interfaced with the microcontroller and operable to continuously store samples of the ECG signal, wherein the microcontroller generates event triggers when the microcontroller identifies at least one of the ECG manifestations in one or more of the ECG traces.

18. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

the firmware also includes arrhythmia features identified in the ECG trace over time,

Wherein the microcontroller generates an event trigger when the microcontroller identifies at least one of the ECG manifestations in one or more of the ECG traces and at least one of the arrhythmias in the ECG traces over time.

19. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

for hypokalemia, the firmware includes an ECG representation that includes one or more of a depressed ST segment and at least one of a prolonged QT interval and a prolonged QTU interval.

20. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

for hypokalemia, the firmware also includes arrhythmia features including ventricular tachycardia,

Wherein the microcontroller generates an event trigger when at least one of the ECG manifestations is identified in one or more of the ECG traces by the microcontroller and ventricular tachycardia is identified in the ECG trace over time.

21. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

for early hyperkalemia, the firmware includes an ECG representation that includes one or more of peak T waves with P-wave broadening or flattening and P-R interval prolongation.

22. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

For moderate hyperkalemia, the firmware includes an ECG representation that includes one or more of QRS complex broadening, peak T waves, longer PR intervals, and lower P waves.

23. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

For fatal hyperkalemia, the firmware includes an ECG representation that includes one or more of a QRS complex resembling a "sine" wave and a developmental wave of a T wave.

24. The subcutaneously insertable cardiac monitor of claim 23, further comprising:

For the fatal hyperkalemia, the firmware also includes arrhythmia features including one or more of pre-death rhythms, pulseless electrical activity PEA, and broad-wave group rhythms,

Wherein the microcontroller generates an event trigger when the microcontroller identifies at least one of the ECG manifestations in one or more of the ECG traces and one or more of a pre-death rhythm, PEA, and broad-cluster rhythm in the ECG trace over time.

25. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

At least one additional ECG sensing electrode additionally disposed on the ventral surface of the implantable housing assembly,

Wherein the firmware includes programmatically selecting one or more pairs of the ECG sensing electrodes.

26. The subcutaneously insertable cardiac monitor of claim 17, wherein the ECG front end circuit is optimized to sense P-wave signals and T-wave signals in the cardiac action potential.

27. The subcutaneously insertable cardiac monitor of claim 17, further comprising:

an interface adapted to communicatively interface the microcontroller with a device for dialysis of a patient.