Assignment on: BIOMEDICAL INSTRUMENTATION

Submitted by KAUSIK BASAK Roll 08MM6103

1. One of the major unsolved problems in heart disease is HEART FAILURE. Your task is to research this disease. Identify technological technological solutions and come up with your own ideas. Focus on the mechnasims, alternative solutions, devices/technology, and comparison/summarize in your opinion and words. Answer : Heart failure (HF) is a condition in which a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. Common causes of heart failure include myocardial infarction and other forms of ischemic heart disease, hypertension, valvular heart disease and cardiomyopathy. Heart failure can cause a large variety of symptoms such as shortness of breath (typically worse when lying flat, which is called orthopnea), coughing, ankle swelling and reduced exercise capacity. Heart failure is often undiagnosed due to a lack of a universally agreed definition and challenges in definitive diagnosis. Treatment commonly consists of lifestyle measures (such as decreased salt intake) and medications, and sometimes devices or even surgery.

Classification There are many different ways to categorize heart failure, including:

the side of the heart involved, (left heart failure versus right heart failure) whether the abnormality is due to contraction or relaxation of the heart (systolic dysfunction vs. diastolic dysfunction) whether the problem is primarily increased venous back pressure (behind) the heart, or failure to supply adequate arterial perfusion (in front of) the heart (backward vs. forward failure)

whether the abnormality is due to low cardiac output with high systemic vascular resistance or high cardiac output with low vascular resistance (low-output heart failure vs. high-output heart failure)

the degree of functional impairment conferred by the abnormality (as in the NYHA functional classification)

Functional classification generally relies on the New York Heart Association Functional Classification.[11] The classes (I-IV) are:

Class I: no limitation is experienced in any activities; there are no symptoms from ordinary activities. Class II: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion. Class III: marked limitation of any activity; the patient is comfortable only at rest. Class IV: any physical activity brings on discomfort and symptoms occur at rest.

This score documents severity of symptoms, and can be used to assess response to treatment. While its use is widespread, the NYHA score is not very reproducible and doesn't reliably predict the walking distance or exercise tolerance on formal testing.[12] In its 2001 guidelines, the American College of Cardiology/American Heart Association working group introduced four stages of heart failure:[13]

Stage A: Patients at high risk for developing HF in the future but no functional or structural heart disorder; Stage B: a structural heart disorder but no symptoms at any stage; Stage C: previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment; Stage D: advanced disease requiring hospital-based support, a heart transplant or palliative care.

Technology solutions Diet and lifestyle measures Pharmacological management There is a significant evidencepractice gap in the treatment of CHF; particularly the underuse of ACE inhibitors and -blockers and aldosterone antagonists which have been shown to provide mortality benefit. Treatment of CHF aims to relieve symptoms, to maintain a euvolemic state (normal fluid level in the circulatory system), and to improve prognosis by delaying progression of heart failure and reducing cardiovascular risk. Drugs used include: diuretic agents, vasodilator agents, positive inotropes, ACE inhibitors, beta blockers, and aldosterone antagonists (e.g. spironolactone). Some drugs which increase heart function, such as the positive inotrope Milrinone, lead to increased mortality, and are contraindicated. Diuretics

Diuretic therapy is indicated for relief of congestive symptoms. Several classes are used, with combinations reserved for severe heart failure:

Loop diuretics (e.g. furosemide, bumetanide) most commonly used class in CHF, usually for moderate CHF.

Thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone, chlorthiazide) may be useful for mild CHF, but typically used in severe CHF in combination with loop diuretics, resulting in a synergistic effect.

Potassium-sparing diuretics (e.g. amiloride) used first-line use to correct hypokalaemia.

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Spironolactone is used as add-on therapy to ACEI plus loop diuretic in severe CHF. Eplerenone is specifically indicated for post-MI reduction of cardiovascular risk.

If a heart failure patient exhibits a resistance to or poor response to diuretic therapy, ultrafiltration or aquapheresis may be needed to achieve adequate control of fluid retention and congestion. The use of such mechanical methods of fluid removal can produce meaningful clinical benefits in patients with diuretic-resistant heart failure and may restore responsiveness to conventional doses of diuretics. American scientists behind the phase I clinical trial of gene therapy for heart failure patients have announced some promising results, including improvements in several measures of the conditions severity.The multi-centre CUPID trial involved a small group of people to test a new treatment, with a view to evaluating its safety, determine a safe dosage range, and identify side effects. The patients enrolled for the study underwent a minimally invasive cardiac catheterization procedure that introduces a specially engineered gene, which stimulates production of an enzyme necessary for the heart to pump more efficiently.

2. Now let us focus on device oriented solution. That is, we would like to come up with suitable device that would assist the mechanically failing heart. Describe one such commercial/research/grade assist device. Provide with reference/patent/commercial information. Identify companies and products. Mention their specification and performance. Answer: Patients with NYHA class III or IV, left ventricular ejection fraction (LVEF) of 35% or less and a QRS interval of 120 ms or more may benefit from cardiac resynchronization therapy (CRT; pacing both the left and right ventricles), through implantation of a bi-ventricular

pacemaker, or surgical remodeling of the heart. These treatment modalities may make the patient symptomatically better, improving quality of life and in some trials have been proven to reduce mortality. The COMPANION trial demonstrated that CRT improved survival in individuals with NYHA class III or IV heart failure with a widened QRS complex on an electrocardiogram.[45] The CARE-HF trial showed that patients receiving CRT and optimal medical therapy benefited from a 36% reduction in all cause mortality, and a reduction in cardiovascular-related hospitalization. Patients with NYHA class II, III or IV, and LVEF of 35% (without a QRS requirement) may also benefit from an implantable cardioverter-defibrillator (ICD), a device that is proven to reduce all cause mortality by 23% compared to placebo in patients who were already optimally managed on drug therapy. Patients with severe cardiomyopathy are at high risk for sudden cardiac death due to ventricular dysrhythmias. Although ICDs deliver electrical shocks to resynchronize heart rhythm which are potentially destressing to the patient, they have not been shown to affect quality of life. The number of (appropriate and inappropriate) shocks seems to be associated to a worse outcome. Although they are expensive, ICDs are potentially cost-effective in this setting. Another current treatment involves the use of left ventricular assist devices (LVADs). LVADs are battery-operated mechanical pump-type devices that are surgically implanted on the upper part of the abdomen. They take blood from the left ventricle and pump it through the aorta. LVADs are becoming more common and are often used by patients who have to wait for heart transplants.

3. Lately pacemaker companies have come up with a pacing therapy for heart failure. The idea is to use electrical stimulation to help with heart failure. Please describe the technology and the solution. Literature, patent, or pacemaker company data will provide you the answer. A pacemaker (or artificial pacemaker, so as not to be confused with the heart's natural pacemaker) is a medical device which uses electrical impulses, delivered by electrodes contacting the heart muscles, to regulate the beating of the heart. The primary purpose of a pacemaker is to maintain an adequate heart rate, either because the heart's native pacemaker is not fast enough, or there is a block in the heart's electrical conduction system. Modern pacemakers are externally programmable and allow the cardiologist to select the optimum pacing modes for individual patients. Some combine a pacemaker and defibrillator in a single implantable device. Others have multiple electrodes stimulating differing positions within the heart to improve synchronisation of the lower chambers of the heart.

Biventricular Pacing (BVP)

A biventricular pacemaker, also known as CRT (cardiac resynchronization therapy) is a type of pacemaker that can pace both the septal and lateral walls of the left ventricle. By pacing both sides of the left ventricle, the pacemaker can resynchronize a heart whose opposing walls do not contract in synchrony, which occurs in approximately 25-50 % of heart failure patients. CRT devices have at least two leads, one in the right ventricle to stimulate the septum, and another inserted through the coronary sinus to pace the lateral wall of the left ventricle. Often, for patients in normal sinus rhythm, there is also a lead in the right atrium to facilitate synchrony with the atrial contraction. Thus, timing between the atrial and ventricular contractions, as well as between the septal and lateral walls of the left ventricle can be adjusted to achieve optimal cardiac function. CRT devices have been shown to reduce mortality and improve quality of life in patients with heart failure symptoms; a LV ejection fraction less than or equal to 35% and QRS duration on EKG of 120 msec or greater. CRT can be combined with an implantable cardioverter-defibrillator (ICD).

4. Surgeons generally recommend myoplasty. Describe the method briefly, and give your opinion on the suitability of this method Vs pacemaker Vs mechanical assist device. Myoplasty is the plastic surgery on muscle in which portions of detached muscles are used, especially in the field of defects or deformities. Cardiac myopiasty offers the advantage of avoiding some of the more common and serious problems associated with cardiac transplant, namely a limited supply of donor hearts, rejection of the donated heart, or infection due to the immunosuppressive agents used to prevent rejection. Advantageously, there is almost always some healthy skeletal or other muscle tissue of the patient that may be translocated and wrapped around the patient's heart. Thus, unlike transplanted hearts (which are in limited supply; are usually only located after diligent searching and long waiting; and, when found, must still be safely transported to a medical facility where the transplant operation can take place), the skeletal or other muscle tissue is with the patient at all times. Further, because the translocated muscle tissue is the patient's own tissue, there is no risk of rejection, as commonly occurs when a heart is transplanted. Using translocated muscle tissue also eliminates the need for lifetime pharmacological therapy with agents designed to prevent rejection, yet which agents have a high incidence of side effects (such as atherosclerosis, altered post-immunocompetence resulting in infection and malignancy). Such agents also tend to be very expensive. Hence, cardiac myopiasty offers a very attractive alternative to cardiac transplant. In order for cardiac myopiasty to be a viable option for a patient suffering from congestive heart failure, there is a need in the art for a quick and safe method or technique of training the muscle tissue that has been translocated around the heart. Such training of the muscle tissue involves repetitive stimulation of the muscle tissue with a stimulation device, e.g., a pulse generator.Heretofore, such stimulation of the muscle tissue has involved two different pacing modes. Initially, to "train" the muscle, a pulse generator has been used with the stimulating electrode in contact with either the muscle or the neurovascular bundle supplying the muscle. The muscle tissue is then stimulated by delivering output pulses at progressively more rapid rates over a period of weeks. After such initial training, the muscle tissue is translocated so as to be wrapped around the heart. The tissue is then stimulated with a dual-chamber pulse generator. One channel of the dual-chamber pulse generator is used for cardiac sensing and pacing and is electrically connected to either the

ventricle or the atrium using either a conventional endocardial or myocardial lead. The other channel is electrically connected to the translocated muscle tissue using, either myocardial or intramuscular lead(s). There are two types of pulse generators currently in use to provide the dualchamber stimulation: a demand-type "DDD" pacemaker, and a dedicated cardiac myostimulator. A myostimulator sytem typically comprises a first intramuscular lead near the nerve branches of the translocated muscle tissue, a second intramuscular lead placed distal from the first to act as the anode, and a third lead for sensing native depolarizations of the heart. Unfortunately, there are several disadvantages associated with using a myostimulator system to train the translocated muscle tissue. First, such system requires a special purpose pulse generator designed to deliver burst pacing. Second, such burst pacing rapidly depletes the battery longevity of the device, causing it to have a relatively short life. Third, the size, weight and cost of the myostimulator device is very high.

5. Give the physiological basis of how either atrial or ventricular fibrillation is produced. Give 5 references citing the very current knowledge/theory on the subject. Fibrillation commonly refers to the rapid, irregular, and unsynchronized contraction of the muscle fibers of the heart. Atrial fibrillation (AF or afib) is the most common cardiac arrhythmia (abnormal heart rhythm) and involves the two upper chambers (atria) of the heart. Its name comes from the fibrillating (i.e. quivering) of the heart muscles of the atria, instead of a coordinated contraction. It can often be identified by taking a pulse and observing that the heartbeats don't occur at regular intervals. However, a conclusive indication of AF is the absence of P waves on an electrocardiogram (ECG), which are normally present when there is a coordinated atrial contraction at the beginning of each heart beat. Atrial fibrillation is diagnosed on an electrocardiogram (ECG), an investigation performed routinely whenever irregular heart beat is suspected. Characteristic findings are the absence of P

waves, with unorganized electrical activity in their place, and irregularity of R-R interval due to irregular conduction of impulses to the ventricles. When ECGs are used for screening, the SAFE trial found that electronic software, primary care physicians and the combination of the two had the following sensitivities and specificities:

Interpreted by software: sensitivity = 83%, specificity = 99% Interpreted by a primary care physician: sensitivity = 80%, specificity = 92% Interpreted by a primary care physician with software: sensitivity = 92%, specificity = 91%

If paroxysmal AF is suspected but an ECG during an office visit only shows a regular rhythm, AF episodes may be detected and documented with the use of ambulatory Holter monitoring (e.g. for a day). If the episodes are too infrequent to be detected by Holter monitoring with reasonable probability, then the patient can be monitored for longer periods (e.g. a month) with an ambulatory event monitor. Ventricular fibrillation (V-fib or VF) is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them tremble rather than contract properly. Ventricular fibrillation is a medical emergency. If the arrhythmia continues for more than a few seconds, blood circulation will cease, and death may occur in a matter of minutes. Ventricular fibrillation has been described as "chaotic asynchronous fractionated activity of the heart" (Moe et al. 1964). A more complete definition is that ventricular fibrillation is a "turbulent, disorganized electrical activity of the heart in such a way that the recorded electrocardiographic deflections continuously change in shape, magnitude and direction". Ventricular fibrillation most commonly occurs within diseased hearts, and, in the vast majority of cases, is a manifestation of underlying ischaemic heart disease. Ventricular fibrillation is also seen in those with cardiomyopathy, myocarditis, and other heart pathologies. In addition, it is seen with electrolyte disturbances and overdoses of cardiotoxic drugs. It is also notable that ventricular fibrillation occurs where there is no discernible heart pathology or other evident cause, the so-called idiopathic ventricular fibrillation.

Idiopathic ventricular fibrillation occurs with a reputed incidence of approximately 1% of all cases of out-of-hospital arrest, as well as 3%-9% of the cases of ventricular fibrillation unrelated to myocardial infarction, and 14% of all ventricular fibrillation resuscitations in patients under the age of 40[11]. It follows then that, on the basis of the fact that ventricular fibrillation itself is common, idiopathic ventricular fibrillation accounts for an appreciable mortality. Recentlydescribed syndromes such as the Brugada Syndrome may give clues to the underlying mechanism of ventricular arrhythmias. In the Brugada syndrome, changes may be found in the resting ECG with evidence of right bundle branch block (RBBB) and ST elevation in the chest leads V1-V3, with an underlying propensity to sudden cardiac death

References
1. "Atrial Fibrillation (for Professionals)". American Heart Association, Inc.. 2008-12-04. Archived from the original on 2009-03-28. http://www.webcitation.org/5fcMx8BUx. 2. "Minimally Invasive Atrial Fibrillation Treatment". Robert Wood Johnson University Hospital. 2008.
http://www.rwjuh.edu/medical_services/min_invasive_atrial_fibrillation.html. Retrieved on 2009-0208. 3. Lewis T (1909). Auricular fibrillation: a common clinical condition. Br Med J 2: 1528 4. Saumarez RC, Heald S, Gill J, et al (1995). "Primary ventricular fibrillation is associated with increased paced right ventricular electrogram fractionation 5. Viskin S, Belhassen B (1990). "Idiopathic ventricular fibrillation". Am. Heart J. 120 (3): 66171

6. What is the current state of art in the implantable pacemaker technology? You should review the literature/web to identify. Mention the key specifications of the latest generation devices. Pacemaker implantation today is minimally invasive surgery. It is done under local anesthesia, and generally takes less than 45 minutes.

After the area under the patient's collarbone is numbed, a small incision is made (usually about 3 inches long,) and a pocket is fashioned in the tissue overlying the muscle. The leads are inserted through a vein near the site of the pocket, and advanced into the heart using fluoroscopy (x-rays) for guidance. The leads are then attached to the generator, the generator is placed in the pocket, and the incision is closed. Once a pacemaker is implanted, it is important to program it. Pacemakers today are extremely flexible devices, and can vary their function according to the precise needs of the patient. But to do this, the doctor needs to program the devices. As noted, pacemaker generators are essentially tiny computers, and like any computer, before they can be optimally useful their software needs to be tweaked to suit the individual user. Pacemakers can be programmed non-invasively, with a handheld device that communicates with the pacemaker through the skin. The programming can be repeated as often as necessary if the patients underlying heart rhythm problem changes. Once the incision completely heals (which takes about 2 4 weeks,) the patient can largely return to a completely normal life. In fact, since pacemakers alleviate the symptoms of bradycardia, many patients find they are able to do even more after a pacemaker is implanted. Periodic pacemaker checks are necessary, to measure the function of the device and the amount of energy left in the battery. The scheduled maintenance for pacemakers generally consists of periodic telephone follow-up (every month or two,) and usually yearly visits to the doctors office. The telephone follow-up is a simple procedure consisting of placing a special transtelephonic follow-up device over the pacemaker, and transmitting data over the telephone. When the battery begins to get low, the doctor schedules an elective pacemaker replacement. This procedure is similar to the implantation procedure, except that usually the pacemaker leads do not need to be replaced. Under local anesthesia, the incision is opened, the generator is detached from the leads and thrown away, a new generator is attached, and the incision is then closed. (This is not merely a "battery change," though doctors sometimes call it that. No batteries are changed; instead, the entire old generator is discarded and a brand new one is placed.)

7. Describe the latest electrode and waveform design that biomedical engineers have come up with? Why do they work better?

Carbon-Nanotube-Based Electrodes for Biomedical Applications

A nanotube array based on vertically aligned nanotubes or carbon nanofibers has been invented for use in localized electrical stimulation and recording of electrical responses in selected regions of an animal body, especially including the brain. There are numerous established, emerging, and potential applications for localized electrical stimulation and/or recording, including treatment of Parkinsons disease, Tourettes syndrome, and chronic pain, and research on electrochemical effects involved in neurotransmission. Carbon-nanotube-based electrodes offer potential advantages over metal macroelectrodes (having diameters of the order of a millimeter) and microelectrodes (having various diameters ranging down to tens of microns) heretofore used in such applications. These advantages include the following:

Stimuli and responses could be localized at finer scales of spatial and temporal resolution, which is at subcellular level, with fewer disturbances to, and less interference from, adjacent regions. There would be less risk of hemorrhage on implantation because nanoelectrode- based probe tips could be configured to be less traumatic. Being more biocompatible than are metal electrodes, carbon-nanotubebased electrodes and arrays would be more suitable for long-term or permanent implantation. Unlike macro- and microelectrodes, a nanoelectrode could penetrate a cell membrane with minimal disruption. Thus, for example, a nanoelectrode could be used to generate an action potential inside a neuron or in proximity of an active neuron zone. Such stimulation may be much more effective than is extra- or intracellular stimulation via a macro- or microelectrode. The large surface area of an array at a micron-scale footprint of non-insulated nanoelectrodes coated with a suitable electrochemically active material containing redox ingredients would make it possible to obtain a pseudocapacitance large enough to dissipate a relatively large amount of electric charge, so that a large stimulation current could be applied at a micron-scale region without exhausting the redox ingredients. Carbon nanotube array is more compatible with the three-dimensional network of tissues. Particularly, a better electricalneural interface can be formed.

A carbon nanotube array inlaid in insulating materials with only the ends exposed is an extremely sensitive electroanalysis tool that can measure the local neurotransmitter signal at extremely high sensitivity and temporal resolution.

8. Describe a)algorithm to detect atrial fibrillation, or b) electrode & shock pulse strategy to terminate atrial fibrillation. Atrial fibrillation is diagnosed on an electrocardiogram (ECG), an investigation performed routinely whenever irregular heart beat is suspected. Characteristic findings are the absence of P waves, with unorganized electrical activity in their place, and irregularity of R-R interval due to irregular conduction of impulses to the ventricles. When ECGs are used for screening, the SAFE trial found that electronic software, primary care physicians and the combination of the two had the following sensitivities and specificities:

Interpreted by software: sensitivity = 83%, specificity = 99% Interpreted by a primary care physician: sensitivity = 80%, specificity = 92% Interpreted by a primary care physician with software: sensitivity = 92%, specificity = 91%

If paroxysmal AF is suspected but an ECG during an office visit only shows a regular rhythm, AF episodes may be detected and documented with the use of ambulatory Holter monitoring (e.g. for a day). If the episodes are too infrequent to be detected by Holter monitoring with reasonable probability, then the patient can be monitored for longer periods (e.g. a month) with an ambulatory event monitor.

Fig: ECG of atrial fibrillation (top) and sinus rhythm (bottom). The purple arrow indicates a P wave, which is lost in atrial fibrillation.