New CHF Drugs
Coreg & beta-blockers
|Archived articles here||Updated July 3, 2006|
November, 1998 - Simvastatin (Zocor) is a cholesterol-lowering drug. We studied the effect of grapefruit juice on Zocor. In a randomized crossover study, 10 healthy volunteers took either 200mL double-strength grapefruit juice or water 3 times a day for 2 days. On day three, each person took 60mg Zocor with either 200mL grapefruit juice or water. Another 200mL was taken 30 and 90 minutes after the Zocor. Then, blood levels of Zocor were measured.
Grapefruit juice increased the average blood level of Zocor 900%! Grapefruit juice (at least in large amounts) should be avoided in patients taking Zocor.
Source: Clin Pharmacol Ther 1998 Nov;64(5):477-83
December 22, 1999 - Doctors don't give enough information to let their patients make informed decisions about treatment. Dr. Clarence Braddock III studied the "informed decision making process" by reviewing audio tapes of primary care doctors and surgeons. The researchers graded these doctors on 7 tasks and decided which tasks were needed for different situations:
Surgeons discussed an average of 2 patient concerns during office visits that only lasted an average of 14 minutes. PCPs discussed 3 patient concerns during office visits lasting an average of 17 minutes. Only 9% of all decisions met the standard for "completely informed" decision-making. The authors write, "None of the intermediate and only 0.5% of the complex decisions were completely informed."
Surgeons (22%) were better at informing their patients than PCPs (19%). Most often left out were discussing alternatives, pros and cons, and uncertainties. Whether the patients understood the decision was almost never examined.
This low level of information giving shows that doctors are out of step with ethical standards. Given the limited time that doctors have with patients, how can they do better informing them about medical decisions? Dr. Michael Barry says, "For decisions that must be faced routinely in office practice, educational materials such as pamphlets and videotapes may help supply basic information."
Source: JAMA 1999;282:2313-2320,2356-2357
April 17, 2002 - According to a survey, almost all Internet users want to be able to reach their doctors online. In this nationwide online survey of 2014 adults, 90% wanted to communicate with their doctors online, 77% wanted to ask questions when no office visit was necessary; and 71% wanted to make appointments, refill prescriptions and get test results online.
Those willing to pay said they would pay up to $10 per month or around $7 per answered e-mail. More than half said that availability of online communication would influence their choice of health plans and choice of doctors (55%).
Because several organizations are already addressing liability and privacy issues, the main barriers to online communication between doctors and patients will be reimbursement and financial incentives for doctors.
Source: Harris Interactive Healthcare News 2002;2(8)
A Harris Interactive Survey April 10, 2002
From: Dr. Laurie Barclay, Medscape & Associated Press
February 29, 2000 - It's very hard to figure out who's studying what in clincial trials. It's also hard for a patient to wade through medspeak to see if a trial might help or if it is too risky.
The USA government now has a web site to help, at http://clinicaltrials.gov/. Congress ordered this registry to use plain-English explanations of how each trial works; and what questions patients should ask to be sure they understand the risks, such as:
Get your doctor to help you sort out the studies you find, says the FDA. If you do enter a study, bring a friend or relative along to hear researchers explain the risks and benefits. "If they don't understand something, it might be that you didn't either," the FDA Commisioner warns. Patients "are very vulnerable when information sounds hopeful. Be willing to ask questions."
The free database so far contains 4000 studies but Congress ordered it to be comprehensive, so more studies - especially drug company trials - will be added. A handful of other Internet sites also list clinical trials. CenterWatch claims over 200,000 visitors a month at www.centerwatch.com. Trials can offer patients cutting-edge therapies. Because participants are supposed to be strictly monitored, they should get above-average care.
There are risks! Patients may not get the actual new treatment, but may get a placebo or standard care instead. A trial can also fail or even be harmful to those in it.
Source: The Associated Press
January 30, 2001 - Regular desktop computers were used by CHFers to access a disease management program through the web. The one-year study included 3 small patient groups. Hospitalizations went down, hospital stays were shorter, compliance went up, and costs went down.
"Ruggerio - one of the company's managers and the study author - said, "Ninety-two percent of the people in this study had never used a computer before, but not only did the technology interest the patients, compliance with entering information every day into the computer was more than 80%."
The study included 69 mostly older patients with moderate to severe CHF, split into 2 groups. The first group of 29 patients, known as the "Web Group," used a personal computer to send their vital signs and symptoms through the Internet into the LifeMasters database. Web users could also contact LifeMasters nurses online.
The second group of 33 patients, known as the "Interactive Voice Response (IVR) Group," used a touch-tone telephone to enter measurements into the same database. IVR users had printed patient education materials and could talk to a LifeMasters nurse by phone. A third group, called the "Non-Intervention Group," did not participate and only got standard care.
Study findings included:
Title: Disease Management and e-Health Can Be Successfully Merged.
April 30, 2001 - In CHF patients, quitting smoking has an effect as strong as drug therapy for reducing risk of death and complications, say Canadian researchers.
Dr. Salim Yusuf studied data on 6704 patients from the SOLVD trial with EF under 35%. This included 1562 current smokers; 1317 ex-smokers who had had not smoked for 2 years or less; 2354 ex-smokers who had not smoked for more than 2 years; and 1471 patients who had never smoked.
During a 41-month follow-up, all-cause mortality was higher in current smokers than in ex-smokers and never-smokers. Risk of death, repeating CHF hospitalizations, and heart attack was also greater among current smokers than in ex-smokers and never-smokers. "It is never too late to quit smoking, even for patients with heart failure," Dr. Stanton Glantz said in an editorial.
Source: J Am Coll Cardiol 2001;37:1677-1684
Heart failure has 3 major stages, according to Dr. Gary Francis:
During remodeling, the heart's main pumping chamber (left ventricle) enlarges and changes shape, getting rounder. The heart also goes through changes at the cell level. This slowly weakens the heart's ability to pump. Apoptosis happens when it shouldn't, causing heart muscle cells to die. All this is partly caused by your neurohormonal system.
The higher neurohormonal activity is in a CHFer, the higher his risk of death. Most heart failure drugs try to control the neurohormonal system. For example, beta-blockers control the sympathetic nervous system. ACE inhibitors and ARBs control angiotensin II. Using endothelin blockers to reduce the effects of endothelin is also being studied.
Beta-blockers and ACE inhibitors together may be able to slow, stop, or even reverse remodeling. In the SOLVD trial, patients taking Vasotec had reduced heart size compared to placebo patients.
A recent report showed that greatly improved heart function after short-term use of an LVAD, followed by its removal in a patient awaiting heart transplant. Not only did heart size go down but there were other improvements at the cell level. This use of LVADs is called "unloading" - reducing the work load of the heart.
A new surgery called SAVER actually removes part of the heart to correct remodeling. A new device called the "mannequin" is now used to further improve results from that surgery. See chfpatients.com/saver.htm for more.
The main problem in heart remodeling seems to be structural changes at the cell level caused by a hyper-active neurohormonal system. Drug treatments show promise in slowing or even reversing this problem. Mechanical unloading through the use of devices such as the LVAD may also reverse the remodeling process.
Title: Halting Remodeling in Congestive Heart Failure
Speaker: Gary S. Francis, MD, The Cleveland Clinic Foundation
American College of Cardiology
May, 2005 - Mental fuzziness is very common in CHFers. However, exactly what causes this mental slowdown is still not certain. We reviewed mental function tests and questionnaires as well as patient characteristics, clinical tests like EF, medications, and other health problems in 1511 CHFers in 81 hospitals throughout Italy.
Every ten years of additional age increased risk of mental dullness. Additional illnesses raised the risk 50%, low blood albumin raised the risk 75%, low blood sodium 50%, abnormal potassium levels 50%, hyperglycemia 30%, anemia almost 40%, and high systolic blood pressure raised risk of mental dysfunction by 60%.
In CHFers with abnormal lab results when admitted to the hospital, correcting blood sugar, potassium, and hemoglobin levels improved mental abilities by the time patients left the hospital. Patients in this study were from the 3-year GIFA survey study. About 35% of the CHFers in that study were found to have some mental function loss.
Title: Correlates of cognitive impairment among patients with heart failure: results of a multicenter survey.
Authors: Zuccala G, Marzetti E, Cesari M, Lo Monaco MR, Antonica L, Cocchi A, Carbonin P, Bernabei R.
Source: Am J Med. 2005 May;118(5):496-502.
April 13, 2000 - Long-term survival of CM patients varies considerably, depending on the cause of the condition. Dr. Edward Kasper studied 1230 CM patients and found a specific cause in about half of them. The patients with idiopathic cardiomyopathy were the control group.
Women with peripartum cardiomyopathy were almost 70% less likely to die during the 4-year study than idiopathic CHFers. Patients with amyloidosis or hemochromatosis were 7 times more likely to die than idiopathic CHFers. HIV-infected patients were 5 times more likely to die, and those with doxorubicin-related (a chemotherapy drug for cancer) CM were 3 times more likely to die during the study than idiopathic CM patients.
"Our study shows that the underlying cause of heart failure is related to survival in many cardiomyopathy patients," the authors say. Dr. Kasper said. "It really pays to identify the cause of a patient's cardiomyopathy."
Title: Underlying Cause of CardiomyopathyPredicts Long-Term Survival
Author: Will Boggs, MD
Source: N Engl J Med 2000;342:1077-1084,1120-1122, Reuters Health
December 15, 2000 - Contrary to current thinking, long-term survival after PPCM may may be better than 90%. Published PPCM death rates range anywhere from 26% to 80%.
Researchers selected 42 women with heart biopsies that confirmed PPCM. Average time from delivering the child to onset of symptoms was 8 days. Sixty-two percent of the women showed evidence of myocarditis, but outcomes were the same whether or not myocarditis occured.
Three patients died (7%) and 3 others required heart transplant during the 8-year follow-up. Only 3 of the women had heart failure that never improved. "In general," the authors say, "prognosis of PPCM patients seems to be better than for other cardiomyopathy patients."
Source: Am Heart J 2000;140:785-791
January 16, 2001 - An online group devoted to EECP treatment is located at http://groups.yahoo.com/group/EECP/. A new study shows that EECP improves the heart's ability to fill during the relaxation phase of its pumping cycle (diastole). The heart's ability to relax between beats strongly affects its pumping.
Also, MUGA scans show that EECP improves blood flow to the heart. This study gives the first clear-cut evidence that EECP improves filling in the hearts of patients with CAD.
Douglas Goldman, Vice-President of Marketing for Vasomedical, said that "one-third of the patients in this study had silent ischemia." Silent ischemia is a temporary shortage of oxygen to the heart that occurs without pain. People with silent ischemia may be more prone to heart attacks without warning.
The study looked at 12 patients with stable CAD and proven ischemia. Patients were evaluated in 2 phases: a control phase to take starting measurements, and a treatment phase in which they received 35 hours of EECP. Treatment effects were measured by a series of physical exams including exercise stress tests, MUGA scans, and more.
EECP improved heart filling. Pressure in the left ventricle went down at the end of the heart's relaxation phase. Peak filling rate and time to maximum filling of the left ventricle improved. All exercise measurements improved. MUGA scans showed improved circulation in the heart after EECP.
EECP is a non-invasive outpatient therapy. It uses cuffs around the legs that fill with air. The cuffs squeeze the legs in rhythm with the patient's own heart beat. This reduces the heart's workload and improves circulation. The treatment is now approved for Medicare reimbursement.
Title: Enhanced External Counterpulsation Improves Exercise Tolerance, Reduces Exercise-Induced Myocardial Ischemia, and Improves Left Ventricular Diastolic Filling in Patients with Coronary Artery Disease
Author: Dr. Hisashi Urano
Source: Business Wire
March 8, 2004 - The FDA has changed its guidelines on EECP treatment, including the new TS4 equipment. Congenital heart diseases, pacemakers, bundle branch block, and significant lung disease are no longer roadblocks to EECP treatment. These were removed from the list of contraindications. Pregnancy and having a known aortic aneurysm requiring surgery are contraindications.
Significant heart valve disease is now a precaution instead of a contraindication. A new precaution was added for patients at high risk of excessive fluid in their lungs.
August 24, 2001 - Researchers studied results from physical exams done on 2569 CHFers in the SOLVD trial. Researchers found that patients with a third heart sound or high jugular vein pressure had greater risk of worsening heart failure or death.
These findings can help doctors tell how severe patients' heart failure is, said Dr. Mark Drazner, the study's author. "Finding these two results on a physical exam identifies patients at increased risk. Whenever a doctor listens to a patient's heart with a stethoscope, he should be listening for a third heart sound," Drazner said. Doctors check jugular vein pressure by watching the pulse in the jugular vein, which is visible in the neck. Increased jugular pressure often means a CHFer is retaining extra fluid.
Doctors' skill at doing physical exams may be declining, partly due to new high-tech imaging machines. "Doctors spend more time learning new technologies, which takes time away from mastering the physical exam. This study shows that the physical exam gives very important information. Doctors should not rely on new technologies so much that they lose sight of how importance a physical exam is," Drazner said.
(Jon's Note - Please note that I had both findings for years and I'm not dead yet, so it's not written in stone. Study abstract here)
Source: N Engl J Med. 2001;345(8):574-581 8/23, 2001 Number 8
Title: Prognostic Importance of Elevated Jugular Venous Pressure and a Third Heart Sound in Patients with Heart Failure
Authors: Mark Drazner, J. Rame, M. Phil, Lynne Stevenson, Daniel Dries
May 15, 2002 - Metformin (brand name is Glucophage) is the most commonly prescribed type II diabetes drug in America. Metformin is linked to lactic acidosis, a life-threatening condition caused by build-up of lactic acid in the blood. Since glucophage's approval in 1995, the FDA has required that the drug be plainly labeled not to be used in patients with kidney dysfunction or heart failure.
Researchers reviewed the charts of patients taking metformin at a university medical center. All patients with 2 or more prescriptions for metformin between January 1 of 2000 and September 30 of 2000 were identified.
Patient records were also reviewed to see if the possibility for problems with the drug had been considered before prescribing it. Pharmacy records identified 241 patients with 2 or more prescriptions for metformin; 100 were randomly selected for chart review.
Twenty-two patients (22%) had either heart failure requiring drug treatment or weak kidney function. Of these 22 patients, 14 had heart failure only, 5 had weak kidneys only, and 3 had both. Only 2 patients had it written in their medical record that a doctor had considered the drug's dangers in their case.
Almost 25% of patients on glucophage had one or more contraindications to using the drug. In the first 14 months after its release in the USA, the FDA saw 47 confirmed cases of lactic acidosis linked to the drug, with a 42% mortality rate. More than 90% of these patients had contraindications to the drug and should not have been taking it.
Metformin is often prescribed to at-risk patients despite the warning. Download the metformin/glucophage prescribing information in pdf here.
Title: Frequency of Inappropriate Metformin Prescriptions
Source: Journal of the American Medical Association 2002;287:2504-2505; Research Letters Section to the Editor
June 18, 2002 - Patients with advanced heart failure who have even mild anemia have worse symptoms, less ability to function, and reduced survival compared to CHFers with normal blood counts. Although anemia is known to be common in heart failure patients, it is assumed that anemia in CHFers doesn't need treatment, said lead author Dr. Gregg Fonarow.
Dr. Fonarow studied data on 1061 patients with advanced heart failure. Patients were class 3 or 4 and had EFs under 40%. Half had ischemic heart failure, 38% had CHF from unknown cause, and 5% from valve disease. The other 7% included alcoholic, hypertrophic, and PPCM.
At study start, patients were divided into 4 groups based on hemoglobin levels:
Thirty percent were anemic. Anemic patients were also more likely to be class 4 and have lower peak oxygen scores. Anemic patients were more likely to have reduced heart function and higher BUN and creatinine (indicating weak kidney function). There was also a link between anemia and risk of death in CHFers.
Dr. Fonarow said, "Anemic heart failure patients had nearly twice the death rate of patients with normal hemoglobin levels." One-year mortality for the most anemic patients was 44%, compared to 36%, 29%, and 26% in the other 3 groups. Risk of death increased 13% for each one g/dL reduction in hemoglobin.
This study suggests that correcting anemia in heart failure patients will reduce symptoms, improve exercise capacity, and prolong survival.
Source: J Am Coll Cardiol 2002;39:1780-1786
March 10, 2003 - Dr. Luis Rodriguez and Dr. Sonia Hernandez-Diaz say recent studies show that NSAID use may double the risk of heart failure hospitalization. They studied a group of British citizens from 40 to 84 years of age. Those with a previous diagnosis of heart failure or cancer were not included.
The people were followed for one year or until their first diagnosis of a heart failure episode or cancer. Analyzing 857 confirmed CHF cases and 5000 matched controls showed that taking NSAIDs made you 1.6 times more likely to be hospitalized for heart failure.
This risk was greater during the first month of NSAID use. The relative risk of heart failure was 1.9 times for patients with a history of high blood pressure, diabetes or kidney failure; and 1.3 times for those without such a history.
Source: Epidemiology 2003;14:240-246
May 28, 2004 - NSAIDs are often used by older people to reduce arthritis symptoms, but increase risk of CHF. A Canadian study shows that the COX2 inhibitor Celebrex (celecoxib) is less likely to trigger heart failure than other NSAIDs. Muhammad Mamdani analyzed previous studies - this was not an actual new trial.
Risk of hospital admission for heart failure was the study endpoint. The study included records of 14,500 people using the COX2 inhibitor Vioxx (rofecoxib), 19,000 using Celebrex, and 5400 people taking non-selective NSAIDs. The control group was 100,000 people not using NSAIDs.
Compared with non-NSAID users, patients on Vioxx had an 80% increase in hospital admission for CHF. People using non-selective NSAIDS had 40% increased admission risk. Celebrex users had no more risk than people not taking NSAIDs.
Source: Intelihealth, The Lancet.
March, 2003 - A new study suggests that the benefits of CHF management by nurses don't amount to much in real-life CHF patients. Almost 300 CHFers admitted to a teaching hospital got either case management or usual care. Unlike previous studies of nurses managing CHFers, patients were of all ages, insurance types, with or without left heart weakness, all heart classes, and with different additional illnesses.
The 90-day re-hospitalization rate for nurse-managed patients and usual-care patients was the same - 37% - said lead author Ann Laramee. Only when specific subgroups were analyzed was benefit seen with nurse management, not in CHFers in general. However, nurse management did cost less.
Overall compliance with prescribed meds was similar in both groups. "In this study, case management compared with usual care did not lower the 90-day readmission rate of CHF patients," the researchers said. "Results suggest that specific case management programs need to be paired with specific patient populations to be effective," the authors conclude.
Source: Arch Intern Med 2003;163:809-817
March 27, 2003 - Using CPAP for sleep apnea in CHFers improves left heart function and lowers blood pressure. Lead author Dr. Douglas Bradley believes that 1/3 of CHFers have sleep apnea, so routine screening of heart failure patients for apnea is a good idea. He said, "The device is inexpensive, easy to use, available now, and has no side effects. You can't ask for more than that."
This trial included just 24 CHFers but Bradley is planning a larger trial. Obstructive sleep apnea or OSA, worsens heart failure. OSA is usually caused by blockage of the throat. CPAP generally uses a mask worn over the nose while sleeping. The mask is connected to an electric pump which moves enough air to keep the throat open, allowing normal breathing during sleep.
An earlier study showed significant improvement in left heart function in 8 CHFers with OSA treated for one month with CPAP. The current randomized controlled trial included 24 CHFers with either ischemic or non-ischemic heart failure.
Patients got either drug therapy alone (12 patients) or drug therapy plus CPAP (12 patients) for one month. Patients on drug therapy alone showed no changes in apnea, daytime blood pressure, heart rate, left heart size, or EF. CPAP patients improved in all these areas.
|Measurement||At Study Start||After One Month of CPAP|
|Systolic blood pressure||126 mmHg||116 mmHg|
|Heart rate||68 bpm||64 bpm|
|Left ventricular end-systolic size||5.5 cm||5.2 cm|
EF improved as much in ischemic as in non-ischemic CHFers; and as much in beta-blocker patients as in non-beta-blocker patients.
Sleep apnea is not always easy to diagnose in CHFers, because they don't always show the usual symptoms of daytime sleepiness and headaches on awakening. The standard way to diagnose OSA is using a sleep study called "polysomnography" done in a sleep clinic.
Hopefully, easier and cheaper ways to diagnose OSA are on the way. One is "ambulatory monitoring" where patients wire themselves up at home before sleeping to get a printout the next day. This would let cardiologists do their own "sleep studies."
Sleep apnea is said to affect 30% of CAD patients, and many CHFers and stroke survivors. Multiple studies report improvement in heart-related outcomes after apnea treatment.
Title: Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea.
Authors: Kaneko Y, Floras JS, Usui K, et al.
Source: N Engl J Med 2003; 348:1233-1241.
March, 2003 - Patients with advanced heart failure have high risk for developing diabetes, starting 6 years after CHF diagnosis. Reduced functional capacity in CHFers may be linked to problems with blood sugar metabolism, said Dr. Alexander Tenenbaum.
Researchers studied the link between heart class and developing diabetes in 2616 non-diabetic patients with previous heart attack or angina over almost 8 years. Patients were between 45 and 74 years old and had a fasting blood glucose (sugar) level less than 7 mmol/L. They were divided into 3 groups based on heart class: class one = 1986 patients, class 2 = 518, and class 3 = 112 patients.
Thirteen percent of class one and 15% of class 2 patients developed diabetes during follow-up, compared to 20% of class 3 CHFers. "Substantial increases in fasting blood glucose level occurred more frequently in patients with advanced heart failure," researchers said.
Class 3 patients were twice as likely to have fasting blood glucose levels of 7 mmol/L or higher at the last visit than class one patients. While diabetics are known to be at higher risk for heart failure, it seems that severe heart failure is also an independent risk factor for developing diabetes.
Source: Am J Med 2003;114:271-275
November 4, 2003 - A new IV therapy reverses blockage of coronary arteries in patients with ACS. This trial tested a synthetic form of "good cholesterol" or HDL.
About 30 years ago, researchers found 40 Italians who were healthy despite having very low levels of HDL. They had a difference in one component of HDL, called apolipoprotein A-I. Their "version" of this substance is called ApoA-I Milano, since this was discovered in Milano, Italy. Usually having low HDL is not good, but these people live longer and have less CAD than expected for their HDL levels.
123 patients with ACS, from 38 to 82 years of age, were screened and 57 patients entered the study. Of 47 patients who completed the study, 11 got placebo, 21 got low-dose, and 15 got high-dose "ETC-216" - the synthetic version of the Italians' HDL version - by IV once a week for 5 weeks.
A test called intravascular ultrasound measured the inside of one coronary artery in each patient. An instrument like a miniature echo tool is used at the end of a catheter during heart cath to take the measurements. If the inside of the artery was bigger, it was due to buildup (blockage) inside the artery being reduced. The tests were done within 2 weeks of ACS happening and again after treatment.
The average size of artery blockages went down one percent in the ETC-216 group compared to an increase of 0.14% in the placebo group. In the combined treatment groups, the absolute reduction in blockage size was 4% from study start.
The study had several limitations. It was a very small study, treatment only lasted 5 weeks, it is unknown if the ultrasound measurements relate to real-life benefit, and no one compared using normal ApoA-I to using ApoA-I Milano.
Source: JAMA. 2003;290:2229-2300, 2322-2324; and Medscape Medical News 2003; and Cleveland Clinic Heart Center.
June, 2003 - Dr. H. Blackledge reported survival trends in 12,220 patients newly admitted to a hospital for heart failure between 1993 and 2001. There was a 44% higher risk of death for each 10 year increase in patient age at admission. There was also a 15% higher risk for men in general, said the researchers.
The good news is that survival rates after hospital discharge have improved by 50% between 1993-1994 when the study began, and 2000-2001.
Source: Heart 2003;89:587-588,605-609,615-620
February 7, 2006 - Researchers studied data from 9,272 elderly people followed from 1970 through 1974, and 31,399 elderly people followed from 1990 through 1994. All patients were members of Kaiser Permanente Northwest Region HMO in Portland, Oregon in the USA.
After adjusting for age and other health problems, risk of death for CHFers went down (improved) during the 20-year period by 33% for men and by 24% for women. Researchers believe the reduced risk of death for CHFers in this time period is partly due to wider ACE inihibitor use.
Jon's Note: Mortality is probably much better than this study suggests. These researchers used data from two periods when beta-blocker use was rare - and when drugs like Inspra and devices like BiV pacemakers did not even exist!
Source: Reuters News
Source: February 6, 2006, doi:10.1161/CIRCULATIONAHA.104.492033 Circulation. 2006;113:799-805.
Title: Changing Incidence and Survival for Heart Failure in a Well-Defined Older Population, 1970-1974 and 1990-1994.
Authors: William H. Barker; John P. Mullooly; William Getchell
June 26, 2003 - Doctors in the United States only take 50% of the recommended steps for treating common illnesses, said Elizabeth McGlynn in Thursday's New England Journal of Medicine. Treatment guidelines give recommended approaches to many common illnesses, including heart failure.
This study looked at 30 medical conditions. Researchers reviewed medical records for 6712 people in 12 cities. They looked only at how often doctors followed the rules, not whether patients suffered any bad effects from their doctors not following guidelines. The guidelines studied were a total of 439 actions or recommendations. "The days of everyone being able to keep it all in your own head are long gone," said Dr. James Martin.
"This study showed a substantial discrepancy between what we say doctors ought to be doing and what they are doing," said Dr. Earl Steinberg. Affordable electronic records to keep track of all the guidelines and recommendations - and which patient needs which of them - might help. Patients also need to be active their own care. That includes educating themselves and asking lots of questions.
Source: The Associated Press
June 23, 2003 - In a study of patients on a hospital cardiology floor, 24 medication errors occurred for every 100 admissions. Data from a pharmacist database at Duke University Medical Center was analyzed. The database recorded all actions made by a pharmacist on the cardiology floor.
Of 15,000 documented actions from 1995 to 2000, 4768 involved medication errors. Thirty-six percent of errors involved the wrong drug, followed closely by giving the wrong dose (35%). In 41% of cases, the errors involved heart drugs.
Errors happened most often right after patients entered the hospital - switching from "outpatient" to "inpatient" drug schedules. Errors also happened more often during the summer months, when new interns begin residency. Total number of errors increased throughout the study period.
The report suggests 2 needed actions: First, the hospital should pay more attention to patients' outpatient medications. Second, new interns need better training before being responsible for hospital medication orders.
Source: Arch Intern Med 2003;163:1461-1466.
December 9, 2003 - In a study of 417 patients with chronic CHF, higher cholesterol level was linked to better survival. On average, patients with a total cholesterol level of 232 mg/dl had a 25% higher survival rate than CHFers with total cholesterol of 193 mg/dl. These results agree with one earlier study that linked lower cholesterol to worse outcome in CHFers.
This was a 2-stage study. The first stage studied the link between cholesterol level and mortality in 114 chronic CHFers treated at a CHF clinic. The link between lower cholesterol and higher mortality was then verified in a second group of 303 CHFers who had their cholesterol levels measured as part of their regular care.
This does not mean that low cholesterol level causes death in heart failure patients! This study did not look backwards to see if cholesterol was low before heart failure developed in these people. It is possible that over time, worsening CHF causes cholesterol to dip downward. If that is true, low cholesterol would be a sign of worsening CHF, not a cause of it.
Heart failure is complex. The body senses danger when the heart starts failing. The body's metabolism shifts gears completely. Hormone levels change drastically and nutrients have a different effect. Since cholesterol is the body's way of packaging and delivering fats throughout the body, low cholesterol levels may be one sign that the body has "canceled" normal operations and is reacting to a "state of emergency."
Some previous trials suggest that cholesterol-lowering drugs called statins may help CHFers, even though they lower cholesterol level. Researchers want to know whether these drugs really help or hurt overall in heart failure patients.
Jon's note: So what about CHFers with coronary artery disease? What cholesterol level should they try to achieve? This trial just raised questions - it did not answer any.
Source: American College of Cardiology; Medscape - The Doctor's Reaction by Dr. Mary Pickett
February 3, 2004 - CE Mark regulatory approval has been given in Europe for Vasogen's immune modulation therapy for chronic heart failure. The new treatment is called Celacade and is still in a phase 3 trial in the USA called ACCLAIM. The therapy is also in a trial for peripheral artery disease.
The 2000-patient ACCLAIM trial was started after a smaller trial showed Celacade to be safe for CHFers. The earlier trial showed reduced risk of death and hospitalization in advanced heart failure patients. Dr. James Young at the Kaufman Center for Heart Failure in Cleveland Clinic is lead investigator for the ACCLAIM trial.
Immune modulation therapy is meant to fight inflammation inside the body. Therapy starts with taking a blood sample from the CHFer. The blood is run through a machine that "stresses" it by heating it to 108° F, "zapping" it with ultraviolet light and then mixing in some ozone gas.
The stressed-out blood cells are then re-injected into the CHFer, where they self-destruct, called apoptosis. The hope is that this little burst of unexpected cell death will signal the immune system to fight inflammation, thus temporarily stopping further damage in the heart. You have to keep taking the treatment regularly, just like you have to keep taking meds.
Source: Vasogen Press Release
Source: The Morning News, January 14, 2003.
September 15, 2004 - Results of a phase 2 trial of immune modulation therapy (named Celacade) have been published. The phase 2 trial included 75 class 3 to class 4 CHFers. They received either Celacade (38 patients) or placebo (37 patients) in a double-blind trial for 6 months. All patients stayed on standard heart failure meds during the trial. Patients were tested for 6-minute walk test, changes in heart class and heart function, and quality of life. Deaths and hospitalization were also tracked.
Celacade did not improve 6-minute walk tests, but 15 Celacade patients and 9 placebo patients improved one heart class. Celacade slightly reduced risk of death and hospitalization. EF did not improve on Celacade but QOL improved very slightly.
Celacade is in a phase 3 trial for treating heart failure and another trial for treating peripheral arterial disease. The heart failure trial is ACCLAIM, which includes 2000 CHFers.
Title: Effects of a novel immune modulation therapy in patients with advanced chronic heart failure. Results of a randomized, controlled, phase II trial.
Authors: Guillermo Torre-Amione, Francois Sestier, Branislav Radovancevic, James Young.
Source: Journal of the ACC, 15 September 2004, Volume 44, Issue 6, pages 1181-1186.
June 28, 2006 - Vasogen says its trial of Celacade for heart failure was stopped early because it did not meet study endpoints. Celacade is the brand name for immune-modulation therapy, which is done once a month. The ACCLAIM trial included 2,414 CHFers in 7 countries. Patients were class 2, 3, or 4. All had EF less than 30%. They were taking all the standard heart failure meds and those who needed them also had BiV pacemakers and ICDs.
The main endpoint was to lower risk of death or heart-related hospitalization. This did not happen in class 3 or class 4 CHFers. However, the 390 treated class 2 CHFers had a 39% relative reduction in risk of death or heart-related hospitalization. The class 2 CHF group had 692 patients but 332 got placebo. The level of "high-sensitivity" proteins in the blood which indicate risk for heart events (CRP) did not change much between the therapy and placebo groups. Celacade was well tolerated and did not cause serious side effects.
Vasogen says completely analyzed results for ACCLAIM will be given at the World Congress of Cardiology 2006, being held from September 2-6 in Barcelona, Spain.
Source: Vasogen Source: Heartwire
November 24, 2004 - Animal trials in mice show that a protein produced in the human body called thyrosin beta 4 may reduce heart muscle damage after a heart attack. Researchers hope to start a trial within 2 years in which paramedics would give the protein to heart attack victims in the ambulance.
The mouse experiment is reported in the journal Nature. Researchers caused heart attacks in 58 mice by constricting blood flow in a major artery leading to the left ventricle. Half the mice were injected with thyrosin beta 4. Forty-five mice survived the procedure and their progress was monitored over 4 weeks.
Mice treated with thyrosin showed 60 to 100% improvement in their heart function. That was twice the improvement of the other mice. The biggest gains in heart function happened within 3 days of their heart attacks.
The thyrosin-treated mice had less scar tissue in their hearts. This suggests that treatment prevented death of heart muscle cells when they were starved of oxygen (ischemia). The heart doesn't normally repair itself and that's why heart attack victims usually get worse over time. However, exactly how thyrosin works is unknown.
Thyrosin is known to help cancer cells spread through the body so a lot more testing is needed before this is used for heart attacks in people. It might be a treatment given only once immediately after a heart attack to reduce heart muscle damage, says the mouse experiment's senior author, Deepak Srivastava.
Source: Associated Press
Source: Nature (journal)
October 7, 2003 - (Jon's note: Beta-blockers "block" beta-adrenergic receptors and ARBs block angiotensin II type 1 receptors.)
Beta receptors and angiotensin II receptors (A2) actually behave like a "receptor complex" allowing single "blocker" drugs to have a double effect, according to this study. Researchers say this means that some CHFers could be better treated with fewer drugs.
Beta receptors and A2 receptors "talk" to each other at the system level through the sympathetic nervous system, said lead author Liza Barki-Harrington. "We wanted to know if they also talk to each other at the cell level through direct receptor-to-receptor interaction."
When treated with beta-blockers, mouse heart cells contracted less than normal when A2 receptors were stimulated. The heart rates of live mice taking an ARB did not increase when beta-receptors were stimulated. This shows that drugs which block the function of one type receptor reduce the activity of both.
Senior author Dr. Howard Rockman says the physical linkage of the receptors could give doctors extra flexibility in treating CHFers. Because ARBs cause fewer side effects, they could be given alone to patients too sick to take beta-blockers. Also, a single potent drug targeting both receptors could replace multiple drugs. Dr. Rockman believes that the success of current CHF meds is partly from the fact that they really affect two receptors, not just one.
The number and "strength" of different receptors varies among patients and with the severity of disease, so a blood test that measured a patient's unique receptor makeup could let his doctor customize treatment. Better understanding of interactions between different linked receptors may help development of highly specific drug therapy for heart failure, say the authors.
Source: Published online before print September 8, 2003, doi:10.1161/01.CIR.0000092166.30360.78.
June 13, 2005 - In CHFers, how you feel is just as important for predicting death or hospitalization as things like diabetes, previous hospitalizations, and ACE inhibitor treatment. This study confirms that in heart failure, poor quality of life helps predict outcome.
Researchers studied 394 patients admitted to any of 4 different hospitals for heart failure-related emergencies. While in the hospital, these patients had physical and mental quality-of-life tests. Over 6 months, 138 of the patients (35%) were re-hospitalized at least once, and 70 died (18%).
More patients with poor scores on the Minnesota Living With Heart Failure questionnaire died. Patients with poor scores on the general health questionnaire SF-36 were more than 1-1/2 times as likely to die or soon be re-hospitalized. Simply finding out how their patients feel may help CHF doctors identify higher-risk patients. Such patients could benefit from closer follow-up.
Title: Health-related quality of life as a predictor of hospital readmission and death among patients with heart failure.
Authors: Rodriguez-Artalejo F, Guallar-Castillon P, Pascual CR, et al. (email@example.com)
Source: Arch Intern Med 2005; 165:1274-1279.
June 15, 2005 - Left heart diastolic dysfunction is common in fat people, especially those with diabetes. Researchers studied 133 obese people who had echocardiograms before gastric bypass surgery. Average age was 48 years. Forty had diabetes and 93 did not. Moderate or severe left heart weakness was found in 24 of 40 obese diabetics (60%) and in 21 of 93 obese non-diabetics (23%).
Title: Prevalence of left ventricular diastolic dysfunction in obese persons with and without diabetes mellitus.
Authors: Di Stante B, Galandauer I, Aronow WS, McClung JA, Alas L, Salabay C, Belkin RN.
Source: Am J Cardiol. 2005 Jun 15;95(12):1527-8.
October 11, 2005 - To see how the bodies of CHFers handle hot weather, researchers studied how the blood vessels in CHFers' forearms responded to external heat compared to healthy people. They also studied core body temperature and sweating response. There were 14 class 2 to class 3 CHFers and a control group of 14 healthy people. All CHFers were stable and on standard heart failure meds.
People in the trial wore special suits lined with tubes that were filled with hot water which gradually raised their internal body temperatures by about 2° F (0.85° C). Another part of the trial studied what happened when their forearms were warmed with water to about 108° F (42° C).
With whole-body heating in the suits, there was much less blood flow in the forearms of CHFers. After just heating the forearm, skin blood vessel response was only half as much in CHFers. Both groups sweated more during heating. Basically, CHFers' blood vessels don't dilate to get rid of heat as much as they should.
What's it all mean? CHFers don't handle heat well. Hey, they should have just asked some of us - we'd have told them that! <g> Our bodies don't get rid of heat nearly as well as healthy people, so we CHFers should stay out of hot environments. If you don't have air conditioning in hot weather, take every other step you can to stay cool. Don't exercise in the heat, either. Do your walking in a mall or somewhere else indoors with controlled temperature.
On the other hand, it is possible that well-designed regular exercise will actually improve this response in CHFers since regular exercise improves endothelial function.
Source: Circulation 2005; 112: 2286-2292.
Title: Effects of heat stress on thermoregulatory responses in congestive heart failure patients.
Authors: Jian Cui, Armin Arbab-Zadeh, Anand Prasad, Sylvain Durand, Benjamin Levine, Craig Crandall.
All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004, 2005, 2006 Jon C.