SVS: Ultrasound Criteria for Carotid Stenosis May Overestimate Severity
By Neil Osterweil, Senior Associate Editor, MedPage TodayReviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
June 07, 2007
Review
BALTIMORE, June 7 -- Patients with internal carotid artery stenosis may be undergoing needless tests and interventions, investigators warned here.
That's because current ultrasound standards for stenoses greater than 50% are based on outmoded information, according to Hisham Bassiouny, M.D., director of the non-invasive vascular lab at the University of Chicago, and colleagues.
Duplex ultrasound velocity thresholds for estimating blood flow through stenotic arteries are too aggressive and tend to overestimate the severity of stenosis, Dr. Bassiouny reported at the Society for Vascular Surgery meeting.
The problem, he said, is that ultrasound standards developed in the 1980s (Strandness criteria) and still in use in the majority of vascular labs in the United States were based on early angiography findings.
"The limitation with angiography is that you had to guess how far the outer wall of the artery was beyond the artery's channel to determine the precise degree of artery blockage," he said. "That was a guess, an estimate. Based upon that subjective estimate, formulas were developed to look at the velocity of blood flow in the artery and determine how much narrowing existed. These formulas became the standard used to this day. However, imaging technology is much better today than when these standards were developed."
The Strandness criteria define greater than 50% stenosis as a peak systolic velocity greater than 125 cm/second, greater spectral broadening throughout systole, and heavy, prominent plaque formation.
The criteria define greater than 80% stenosis as a peak systolic velocity > 125 cm/second, marked spectral broadening and turbulence, severe plaque formation, and end diastolic velocity elevated more than 140cm/second.
To see whether the criteria held up with the use of modern equipment, Dr. Bassiouny and colleagues first compared B-mode ultrasound and computed tomography angiography images performed on 74 patients with internal carotid artery stenosis, in order to validate the accuracy of the ultrasound measurements.
They then evaluated 337 patients with either mild, moderate, or severe internal carotid artery stenoses, looking at the minimal residual lumen and the corresponding outer internal carotid artery or bulb diameter on longitudinal and transverse images. Patients with contralateral occlusion were excluded from the analysis, as were calcified artery segments.
In both the validation sample and the larger study, the highest peak systolic velocity, end diastolic velocity, and ratio of the internal carotid artery to the common carotid artery (ICA/CCA ratio) were recorded.
The investigators determined the optimum threshold for each hemodynamic parameter using receiver operating characteristic curves to predict stenosis of 50% or greater (in 281 patients) and of 80% or greater (in 62 patients) bulb internal carotid artery stenosis.
They found that "there was excellent agreement between B-mode ultrasound and computed tomography angiography (r=0.9, P=0.002)."
But when they looked at the sensitivity, specificity, and positive- and negative-predictive value of B-mode ultrasound, they found that the Strandness criteria would rope in too many patients who did not have serious stenosis.
When both a peak systolic velocity equal to or greater than 155 cm/second and an ICA/CCA ratio of 2 or greater were combined for the detection of at least 50% internal carotid artery stenosis, a positive predictive value of 97% and an accuracy of 82% were obtained. For a stenosis of 80% or greater, and end diastolic velocity of 140 cm/second, a peak systolic velocity 370 cm/second or greater, and an ICA/CCA ratio of 6 or more had acceptable probability values.
"Compared to established velocity thresholds commonly applied in practice (Strandness criteria), a substantially higher peak systolic velocity (155 vs. 125 cm/second) was more accurate for detecting ≥ 50% bulb ICA stenosis," the authors wrote.
"In combination, a PSV of ≥155 cm/second and an ICA/CCA ratio of 2 have excellent predictive value for this stenosis category," they said. "For an ≥ 80% ICA stenosis, an end diastolic velocity of 140 cm/second, a peak systolic velocity of ≥ 370 cm/second, and an ICA/CCA ratio of ≥ 6 are equally reliable."
The authors said that current criteria for duplex ultrasound detection of 50% or greater internal carotid artery stenosis may overestimate carotid bifurcation disease.
"As a result, we've changed the standards in our vascular lab," Dr. Bassiouny said. "We hope these new standards will be adopted everywhere. Such a move would save money and spare at least some patients from unnecessary procedures and tests."
Primary source: Vascular Annual Meeting 2007
Source reference: Shalaan WE et al. "Reappraisal Of Internal Carotid Artery Stenosis Velocity Thresholds Utilizing High-Resolution B-Mode Ultrasound Validated With CTA: Do Current Practice Thresholds Overestimate Carotid
Saturday, June 9, 2007
Metabolic Syndrome Linked to Compromised Heart Structure and Function
Metabolic Syndrome Linked to Compromised Heart Structure and Function
Review
PORTO, Portugal, June 7 -- As metabolic syndrome becomes more severe, symptomatic heart failure and several cardiac structural and functional abnormalities may increase progressively, researchers here reported.
This association was independent of the 10-year predicted risk of coronary heart disease by the standard Framingham risk score for indirect indices of diastolic dysfunction, although not systolic function, Ana Azevedo, Ph.D., of the University of Porto here, and colleagues reported online in BMC Cardiovascular Disorders.
There was been much debate about the usefulness of the metabolic syndrome in cardiovascular risk prediction, namely whether it adds information to that provided by its individual components, and whether it adds to alternative prediction tools, including the widely used Framingham risk score, Dr. Azevedo wrote.
The current findings came from a cross-sectional study of a random sample of the urban population of Porto, which included 684 participants, ages 45 or older, recruited from 2001 to 2003.
Data were collected by a structured clinical interview with a physician, ECG, and a transthoracic M-mode and 2D echocardiogram.
Metabolic syndrome was defined according to the National Cholesterol Education Program. It included:
Waist circumference more than 102 cm in men and more than 88 cm in women.
Fasting serum triglycerides of 150 mg/dL or more.
High-density lipoprotein (HDL) cholesterol of less than 40 mg/dL in men and less than 50 mg/dL in women.
High blood pressure: systolic blood pressure of 130 mm Hg or higher and/or diastolic blood pressure of 85 mm Hg or higher, antihypertensive drug treatment.
High glucose levels: fasting serum glucose pf 110 mg/dL or higher, or clinical diagnosis of diabetes.
The association between the number of features of the metabolic syndrome and the cardiac structural and functional abnormalities was adjusted for age and gender, the 10-year predicted risk of coronary heart disease by the Framingham risk score, and adjusting for age, gender, and systolic blood pressure.
There was a positive association between the number of elements in the metabolic syndrome and features of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables when adjusting for age and gender.
Measures of left-ventricular geometry patterns, left-atrial diameter, and diastolic dysfunction maintained this trend when taking into account the 10-year predicted risk of coronary heart disease by the Framingham score as an independent variable, while left ventricular systolic dysfunction did not, the researchers said.
Measures of left-ventricular diastolic dysfunction, and mean left-ventricular mass, left-ventricular diameter, and left-atrial diameter increased significantly with increasing numbers of metabolic syndrome features when additionally adjusting for systolic blood pressure as a continuous variable, the researchers reported. Left ventricular systolic dysfunction did not support this trend, they said.
Of all the participants, 19.7% had metabolic syndrome, which was more common among women than men.
High blood pressure was by far the most prevalent single component of the syndrome and affected about 75% of all participants. In this group 80% had hypertension (140/90 mmHg) or used antihypertensive medication.
Men had a higher predicted risk of coronary heart disease, according to the Framingham prediction score.
Cardiac abnormalities were also fairly common in this sample and heart failure (stage C) affected 8.4% of the women and 5.2% of the men.
Concurrence of the various components of the metabolic syndrome increased significantly with age and the syndrome was also significantly and strongly associated with the predicted 10-years risk of coronary heart disease by the Framingham score. Prevalence raged from 6.5 for one metabolic syndrome, for example, to 18.4 for four to five features (P for trend=0.002).
There was a positive association between the degree of the metabolic syndrome -- assessed as the number of concurrently present components -- and measures of cardiac structure (left-ventricular diameter and mass, posterior wall height and interventricular septum height) and function.
In a subsample analysis of 541 patients younger than 75 with no coronary heart disease, the adjusted prevalence of left ventricular systolic dysfunction increased with increasing degree of metabolic syndrome, but the association was not statistically significant (P for trend 0.19) when adjusting for the Framingham risk score, the researchers reported.
Importantly, the researchers said, early asymptomatic stages of cardiac dysfunction increased progressively with the severity of the metabolic syndrome, independent of systolic blood pressure.
The statistical association with increasing number of features of metabolic syndrome can be explained by the increasing impact of multiple independent risk factors and does not necessarily mean that there is synergism, the researchers said.
Given the tendency of individual factors to aggregate, the prevalence of each component in isolation was very low, except for high blood pressure. Therefore, it was not possible to estimate the sole effect of each factor, in comparison with the absence of all factors, the researchers said.
From the clinical and public health perspective, it has been questioned whether the metabolic syndrome improves cardiovascular risk prediction, beyond previously used tools such at the diabetes predicting model or the Framingham risk score for coronary heart disease, the researchers said.
One must keep in mind, they said, that coronary heart disease is not the only determinant of systolic and diastolic dysfunction. Adjusting for the Framingham risk score amounts to assessing the effect of features of the metabolic syndrome not considered in the Framingham score, such as obesity and triglycerides, among other features, the researchers noted.
If there is increasing insulin resistance with increasing degree of metabolic syndrome, there might be a mitogenic stimulus for cardiac hypertrophy, the researchers wrote. It is not surprising therefore that cardiac structural features were significantly associated with increasing severity of the metabolic syndrome, even when adjusting for the Framingham risk score.
The main limitation of the study, the investigators said, is its relatively small sample size leading to few outcomes in certain categories, such as left ventricular systolic dysfunction, and difficulty assessing interactions within the metabolic syndrome. The cross-sectional design was also not the ideal approach for assessing causality.
Given that increasing concurrence of the metabolic syndrome factors might be only a proxy for higher blood pressure, it is a strength of this study that the reported associations were not explained by blood pressure level, the researchers said.
This association between the metabolic syndrome and compromised structure and function of the heart was independent of the 10-year predicted risk of coronary heat disease by the Framingham risk score for indirect indices of diastolic dysfunction, although not systolic function, the investigators said.
"Metabolic syndrome may help predict and increased cardiovascular risk beyond that predicted by the more frequently use Framingham risk score," Dr. Azevedo wrote.
No financial disclosures were reported. The study was funded by the Science and Technology Foundation.
Primary source: BMC Cardiovascular DisordersSource reference: Azevedo A, et al "Increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities: cross-sectional study of the general population" BMC Cardiovascular Disorders 2007.
Review
PORTO, Portugal, June 7 -- As metabolic syndrome becomes more severe, symptomatic heart failure and several cardiac structural and functional abnormalities may increase progressively, researchers here reported.
This association was independent of the 10-year predicted risk of coronary heart disease by the standard Framingham risk score for indirect indices of diastolic dysfunction, although not systolic function, Ana Azevedo, Ph.D., of the University of Porto here, and colleagues reported online in BMC Cardiovascular Disorders.
There was been much debate about the usefulness of the metabolic syndrome in cardiovascular risk prediction, namely whether it adds information to that provided by its individual components, and whether it adds to alternative prediction tools, including the widely used Framingham risk score, Dr. Azevedo wrote.
The current findings came from a cross-sectional study of a random sample of the urban population of Porto, which included 684 participants, ages 45 or older, recruited from 2001 to 2003.
Data were collected by a structured clinical interview with a physician, ECG, and a transthoracic M-mode and 2D echocardiogram.
Metabolic syndrome was defined according to the National Cholesterol Education Program. It included:
Waist circumference more than 102 cm in men and more than 88 cm in women.
Fasting serum triglycerides of 150 mg/dL or more.
High-density lipoprotein (HDL) cholesterol of less than 40 mg/dL in men and less than 50 mg/dL in women.
High blood pressure: systolic blood pressure of 130 mm Hg or higher and/or diastolic blood pressure of 85 mm Hg or higher, antihypertensive drug treatment.
High glucose levels: fasting serum glucose pf 110 mg/dL or higher, or clinical diagnosis of diabetes.
The association between the number of features of the metabolic syndrome and the cardiac structural and functional abnormalities was adjusted for age and gender, the 10-year predicted risk of coronary heart disease by the Framingham risk score, and adjusting for age, gender, and systolic blood pressure.
There was a positive association between the number of elements in the metabolic syndrome and features of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables when adjusting for age and gender.
Measures of left-ventricular geometry patterns, left-atrial diameter, and diastolic dysfunction maintained this trend when taking into account the 10-year predicted risk of coronary heart disease by the Framingham score as an independent variable, while left ventricular systolic dysfunction did not, the researchers said.
Measures of left-ventricular diastolic dysfunction, and mean left-ventricular mass, left-ventricular diameter, and left-atrial diameter increased significantly with increasing numbers of metabolic syndrome features when additionally adjusting for systolic blood pressure as a continuous variable, the researchers reported. Left ventricular systolic dysfunction did not support this trend, they said.
Of all the participants, 19.7% had metabolic syndrome, which was more common among women than men.
High blood pressure was by far the most prevalent single component of the syndrome and affected about 75% of all participants. In this group 80% had hypertension (140/90 mmHg) or used antihypertensive medication.
Men had a higher predicted risk of coronary heart disease, according to the Framingham prediction score.
Cardiac abnormalities were also fairly common in this sample and heart failure (stage C) affected 8.4% of the women and 5.2% of the men.
Concurrence of the various components of the metabolic syndrome increased significantly with age and the syndrome was also significantly and strongly associated with the predicted 10-years risk of coronary heart disease by the Framingham score. Prevalence raged from 6.5 for one metabolic syndrome, for example, to 18.4 for four to five features (P for trend=0.002).
There was a positive association between the degree of the metabolic syndrome -- assessed as the number of concurrently present components -- and measures of cardiac structure (left-ventricular diameter and mass, posterior wall height and interventricular septum height) and function.
In a subsample analysis of 541 patients younger than 75 with no coronary heart disease, the adjusted prevalence of left ventricular systolic dysfunction increased with increasing degree of metabolic syndrome, but the association was not statistically significant (P for trend 0.19) when adjusting for the Framingham risk score, the researchers reported.
Importantly, the researchers said, early asymptomatic stages of cardiac dysfunction increased progressively with the severity of the metabolic syndrome, independent of systolic blood pressure.
The statistical association with increasing number of features of metabolic syndrome can be explained by the increasing impact of multiple independent risk factors and does not necessarily mean that there is synergism, the researchers said.
Given the tendency of individual factors to aggregate, the prevalence of each component in isolation was very low, except for high blood pressure. Therefore, it was not possible to estimate the sole effect of each factor, in comparison with the absence of all factors, the researchers said.
From the clinical and public health perspective, it has been questioned whether the metabolic syndrome improves cardiovascular risk prediction, beyond previously used tools such at the diabetes predicting model or the Framingham risk score for coronary heart disease, the researchers said.
One must keep in mind, they said, that coronary heart disease is not the only determinant of systolic and diastolic dysfunction. Adjusting for the Framingham risk score amounts to assessing the effect of features of the metabolic syndrome not considered in the Framingham score, such as obesity and triglycerides, among other features, the researchers noted.
If there is increasing insulin resistance with increasing degree of metabolic syndrome, there might be a mitogenic stimulus for cardiac hypertrophy, the researchers wrote. It is not surprising therefore that cardiac structural features were significantly associated with increasing severity of the metabolic syndrome, even when adjusting for the Framingham risk score.
The main limitation of the study, the investigators said, is its relatively small sample size leading to few outcomes in certain categories, such as left ventricular systolic dysfunction, and difficulty assessing interactions within the metabolic syndrome. The cross-sectional design was also not the ideal approach for assessing causality.
Given that increasing concurrence of the metabolic syndrome factors might be only a proxy for higher blood pressure, it is a strength of this study that the reported associations were not explained by blood pressure level, the researchers said.
This association between the metabolic syndrome and compromised structure and function of the heart was independent of the 10-year predicted risk of coronary heat disease by the Framingham risk score for indirect indices of diastolic dysfunction, although not systolic function, the investigators said.
"Metabolic syndrome may help predict and increased cardiovascular risk beyond that predicted by the more frequently use Framingham risk score," Dr. Azevedo wrote.
No financial disclosures were reported. The study was funded by the Science and Technology Foundation.
Primary source: BMC Cardiovascular DisordersSource reference: Azevedo A, et al "Increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities: cross-sectional study of the general population" BMC Cardiovascular Disorders 2007.
Low serum K tied to increased mortality risk in heart failure
Low serum K tied to increased mortality risk in heart failure
Hypokalemia is associated with an increased mortality risk independently of NYHA functional class, drugs used in therapy, and use of potassium supplements, according to a post hoc analysis of data from a randomized trial conducted in the 1990s.
Low serum potassium in HF may be caused by diuretic therapy or may be a marker of increased neurohormonal activity and disease progression according to the authors, who say their study has implications for contemporary HF management. Its findings argue against the use of diuretics in euvolemic patients with milder HF and for an emphasis on potassium-sparing diuretics in those with more symptomatic disease and volume overload, write Dr Ali Ahmed (University of Alabama, Birmingham) and associates.
Their analysis, which defined hypokalemia as a serum potassium <4 mEq/L, is based on patients followed for 32 months in the US-Canadian Digitalis Investigation Group (DIG) trial who had levels <5.5 mEq/L. The DIG trial, which predated the recommended use of beta blockers in heart failure, had entered patients with chronic systolic or diastolic HF of any etiology. The current report appears in the June 2007 issue of the European Heart Journal.
The cohort's 1187 patients with serum potassium <4 mEq/L were matched with the same number who had higher levels based on propensity scores encompassing a broad range of demographic, clinical, and treatment-related factors. Nearly all of those features became covariates in an analysis that showed low potassium to be independently associated with increased all-cause and cardiovascular mortality and death due to progressive HF. Similar but nonsignificant trends were seen for all-cause, cardiovascular, and MI- and stroke-related hospitalization.
Mortality risks associated with serum potassium <4 mEq/L in heart failure
ALL-CAUSE MORTALITY: HR 1.25 95% CI 1.07 – 1.46 p 0.006
CV MORTALITY: HR 1.27 95% CI 1.06 – 1.51 p 0.009
DEATH FROM PROGRESIVE HF: HR 1.36 95% CI 1.05 – 1.75 p 0.020
Hypokalemia hasn't been well defined in heart failure, although in the hypertension literature the definition has been variously said to be serum potassium of <3.5 mEg/L or <4.0 mEq/L, according to Ahmed. The current analysis supports a minimum of 4 mEq/L up to at least 5.5 mEq/L as the optimal safe range for HF patients, consistent with other proposals in the literature, he told heartwire.
Based on their findings and the established evidence base, Ahmed and his colleagues recommend the following treatment approaches:
Avoid diuretics in patients in NYHA class 1-2 who are receiving contemporary recommended drug therapy and have adequate fluid balance.
Patients in NYHA 3-4 heart failure with volume overload should receive diuretics, which could include spironolactone (or potentially eplerenone for post-MI patients) to help prevent hypokalemia.
Potassium supplements may be an alternative to aldosterone antagonists.
"But we think it might be safer to give spironolactone [instead of potassium supplements] because of its proven benefit in terms of reducing mortality," Ahmed said. "No one knows what potassium supplements will do [in heart failure]."
How relevant are findings based on the vintage DIG trial to today's generation of heart-failure patients who, unlike those in DIG, are taking beta blockers or are generally supposed to be taking them? Those drugs are grossly underused in heart failure today, Ahmed noted, observing that about one half of HF is chronic and only about one half of HF patients who should receive beta blockers actually get them. That, he said, would mean the drugs are today used in only about one fourth of HF patients and, therefore, the DIG analysis likely applies to about three fourths of heart failure today. "That's the way I look at it."
SOURCES:
Ahmed A, Zannad F, Love TE, et al. A propensity-matched study of the association of low serum potassium levels and mortality in chronic heart failure. Eur Heart J 2007;
Hypokalemia is associated with an increased mortality risk independently of NYHA functional class, drugs used in therapy, and use of potassium supplements, according to a post hoc analysis of data from a randomized trial conducted in the 1990s.
Low serum potassium in HF may be caused by diuretic therapy or may be a marker of increased neurohormonal activity and disease progression according to the authors, who say their study has implications for contemporary HF management. Its findings argue against the use of diuretics in euvolemic patients with milder HF and for an emphasis on potassium-sparing diuretics in those with more symptomatic disease and volume overload, write Dr Ali Ahmed (University of Alabama, Birmingham) and associates.
Their analysis, which defined hypokalemia as a serum potassium <4 mEq/L, is based on patients followed for 32 months in the US-Canadian Digitalis Investigation Group (DIG) trial who had levels <5.5 mEq/L. The DIG trial, which predated the recommended use of beta blockers in heart failure, had entered patients with chronic systolic or diastolic HF of any etiology. The current report appears in the June 2007 issue of the European Heart Journal.
The cohort's 1187 patients with serum potassium <4 mEq/L were matched with the same number who had higher levels based on propensity scores encompassing a broad range of demographic, clinical, and treatment-related factors. Nearly all of those features became covariates in an analysis that showed low potassium to be independently associated with increased all-cause and cardiovascular mortality and death due to progressive HF. Similar but nonsignificant trends were seen for all-cause, cardiovascular, and MI- and stroke-related hospitalization.
Mortality risks associated with serum potassium <4 mEq/L in heart failure
ALL-CAUSE MORTALITY: HR 1.25 95% CI 1.07 – 1.46 p 0.006
CV MORTALITY: HR 1.27 95% CI 1.06 – 1.51 p 0.009
DEATH FROM PROGRESIVE HF: HR 1.36 95% CI 1.05 – 1.75 p 0.020
Hypokalemia hasn't been well defined in heart failure, although in the hypertension literature the definition has been variously said to be serum potassium of <3.5 mEg/L or <4.0 mEq/L, according to Ahmed. The current analysis supports a minimum of 4 mEq/L up to at least 5.5 mEq/L as the optimal safe range for HF patients, consistent with other proposals in the literature, he told heartwire.
Based on their findings and the established evidence base, Ahmed and his colleagues recommend the following treatment approaches:
Avoid diuretics in patients in NYHA class 1-2 who are receiving contemporary recommended drug therapy and have adequate fluid balance.
Patients in NYHA 3-4 heart failure with volume overload should receive diuretics, which could include spironolactone (or potentially eplerenone for post-MI patients) to help prevent hypokalemia.
Potassium supplements may be an alternative to aldosterone antagonists.
"But we think it might be safer to give spironolactone [instead of potassium supplements] because of its proven benefit in terms of reducing mortality," Ahmed said. "No one knows what potassium supplements will do [in heart failure]."
How relevant are findings based on the vintage DIG trial to today's generation of heart-failure patients who, unlike those in DIG, are taking beta blockers or are generally supposed to be taking them? Those drugs are grossly underused in heart failure today, Ahmed noted, observing that about one half of HF is chronic and only about one half of HF patients who should receive beta blockers actually get them. That, he said, would mean the drugs are today used in only about one fourth of HF patients and, therefore, the DIG analysis likely applies to about three fourths of heart failure today. "That's the way I look at it."
SOURCES:
Ahmed A, Zannad F, Love TE, et al. A propensity-matched study of the association of low serum potassium levels and mortality in chronic heart failure. Eur Heart J 2007;
Friday, June 8, 2007
Stress Echocardiography
From British Journal of Cardiology
Stress Echocardiography -- Current Status
More:
Link: http://www.medscape.com/viewarticle/557423?rss
Stress Echocardiography -- Current Status
More:
Link: http://www.medscape.com/viewarticle/557423?rss
Electrophysiology roundup
Electrophysiology roundup
A recent review from the Journal of the American College of Cardiology on developments in the field of electrophysiology during the year 2006 was posted in Medscape May 21. I thought it was worth linking here, as it contains several items of general clinical interest. Some highlights follow.
Cardiac channel disorders continue to garner interest. Despite the discovery of new mutations leading to the long QT syndrome (LQTS) some 25% of patients with LQTS have no identifiable genetic abnormality. Brugada syndrome is increasingly well understood. The channelopathies of Brugada syndrome appear to cause a gradient between endocardium and epicardium caused by disparities in phase 1 of their respective action potentials. In contrast to the LQTS, relatively few patients with Brugada syndrome (20%-30%) have an identified genetic abnormality.
One study referenced in the review is interesting, to me anyway, not because of any immediate clinical relevance but because it’s an example herbal research done right. Investigators created a Brugada syndrome phenotype in isolated perfused canine right ventricular tissue. Drawing on prior research showing that dimethyl lithospermate B (dmLSB), a minor component of the root extract of the Danshen plant, is capable of decreasing inactivation of the sodium current INa, the researchers demonstrated reversal of the Brugada phenotype by adding dmLSB to the perfusate. Basic research such as this may pave the way for novel drug therapies for cardiac channelopathies
Recent research in Brugada syndrome has also made it increasingly evident that the electrocardiographic findings may fluctuate over time, often necessitating multiple tracings to diagnose, classify and risk stratify patients.
Genetic abnormalities, both germ line and somatic, also underlie non lethal conditions. Recent findings relating to genetic causes of sick sinus syndrome and somatic mutations in atrial fibrillation were presented.
Finally, nonantiarrhythmic drugs are increasingly being found to prevent arrhythmias. A meta-analysis cited in the review found that treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers decreases the new onset of atrial fibrillation in patients with and without heart failure. The review cited prior studies indicating that statin drugs prevent atrial fibrillation and a recent study of patients with coronary artery disease and implanted defibrillators showing that administration of 80mg daily of atorvastatin decreases episodes of device intervention by 50%.
Link: http://doctorrw.blogspot.com/
A recent review from the Journal of the American College of Cardiology on developments in the field of electrophysiology during the year 2006 was posted in Medscape May 21. I thought it was worth linking here, as it contains several items of general clinical interest. Some highlights follow.
Cardiac channel disorders continue to garner interest. Despite the discovery of new mutations leading to the long QT syndrome (LQTS) some 25% of patients with LQTS have no identifiable genetic abnormality. Brugada syndrome is increasingly well understood. The channelopathies of Brugada syndrome appear to cause a gradient between endocardium and epicardium caused by disparities in phase 1 of their respective action potentials. In contrast to the LQTS, relatively few patients with Brugada syndrome (20%-30%) have an identified genetic abnormality.
One study referenced in the review is interesting, to me anyway, not because of any immediate clinical relevance but because it’s an example herbal research done right. Investigators created a Brugada syndrome phenotype in isolated perfused canine right ventricular tissue. Drawing on prior research showing that dimethyl lithospermate B (dmLSB), a minor component of the root extract of the Danshen plant, is capable of decreasing inactivation of the sodium current INa, the researchers demonstrated reversal of the Brugada phenotype by adding dmLSB to the perfusate. Basic research such as this may pave the way for novel drug therapies for cardiac channelopathies
Recent research in Brugada syndrome has also made it increasingly evident that the electrocardiographic findings may fluctuate over time, often necessitating multiple tracings to diagnose, classify and risk stratify patients.
Genetic abnormalities, both germ line and somatic, also underlie non lethal conditions. Recent findings relating to genetic causes of sick sinus syndrome and somatic mutations in atrial fibrillation were presented.
Finally, nonantiarrhythmic drugs are increasingly being found to prevent arrhythmias. A meta-analysis cited in the review found that treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers decreases the new onset of atrial fibrillation in patients with and without heart failure. The review cited prior studies indicating that statin drugs prevent atrial fibrillation and a recent study of patients with coronary artery disease and implanted defibrillators showing that administration of 80mg daily of atorvastatin decreases episodes of device intervention by 50%.
Link: http://doctorrw.blogspot.com/
Blood-pressure changes with acupuncture comparable to ACE-inhibitor monotherapy
Blood-pressure changes with acupuncture comparable to ACE-inhibitor monotherapy
Erlangen, Germany - A study billed as the first rigorous, randomized trial in the West to test acupuncture against a sham needle technique to treat hypertension suggests that, performed properly, acupuncture may produce blood-pressure changes on a par with monotherapy in mild to moderate hypertension.
"It's certainly not like a wonder drug; it's not a massive effect, but it's a clear effect," lead investigator Dr Frank A Flachskampf (Universitätsklinikum Erlangen, Germany) told heartwire.
Smaller randomized trials have been performed in China, with mixed results, while one randomized study in the West found no difference in blood-pressure lowering between traditional Chinese acupuncture, standardized acupuncture, and a sham procedure, the authors note. This earlier study did not use ambulatory blood-pressure measurements, believed to be superior to office-based measurements.
Results of their study are published online June 4, 2007 in Circulation.
Needlework
For the study, 160 outpatients with uncomplicated, mild to moderate hypertension were randomized to six weeks of acupuncture performed by Chinese medicine practitioners, trained in China, or to a sham procedure. In both arms, patients underwent 22 sessions, each 30 minutes in length. By the end of the six weeks, 24-hour ambulatory systolic and diastolic blood pressures were significantly reduced from baseline in the acupuncture-treated patients (5.4 mm Hg and 3.0 mm Hg, respectively), and this change was also significantly different from values in the sham-treated patients, in whom no meaningful changes were seen.
After three and six months, however, the blood-pressure reductions disappeared, leading investigators to conclude that ongoing acupuncture treatments would be required to maintain the blood-pressure reductions.
"The main finding is that for the first time in a reasonably sized but still relatively small randomized study, this establishes beyond a reasonable doubt that acupuncture lowers blood pressure," Flachskampf commented. "It's a modest but undeniable effect on both systolic and diastolic blood pressure."
The extent of the blood-pressure reductions are comparable to those seen with ACE-inhibitor monotherapy or aggressive lifestyle changes, including radical salt restrictions, he added.
A "demanding" alternative to drugs
Flachskampf had some caveats, acknowledging that the regular acupuncture sessions used in the study represent a significant time investment: each acupuncture session lasted 30 minutes—not including transportation and administrative time—and took place several times a week. The study subjects were also reasonably healthy, with no other major risk factors and with only mild to moderate hypertension.
"This is clearly something that would probably not work as well with very sick people or people with blood pressure at dangerous levels," he said. "We cannot easily extrapolate to people, for example, with complicated hypertension who have had a myocardial infarction."
Flachskampf believes, however, that acupuncture likely represents an attractive option in specific patients, particularly those averse to taking medical therapy who are open to so-called "alternative" medicine.
"This is probably only for people who somehow relate to this spiritually, who say I am profoundly against taking drugs and I'm very fond of Oriental wisdom or things like that," Flachskampf told heartwire. "I don't want to make a joke about this, but this certainly needs more compliance than taking two or three pills a day. It's much more demanding."
Unlike drugs, acupuncture appeared to have few or no side effects, although two people complained that the needles were painful. "Clearly, many millions of Chinese get acupuncture without any major problems so I think this is really a minor point," Flachskampf observed.
Source:
Flachskampf FA, Gallasch J, Gefeller O, et al. Randomized trial of acupuncture to lower blood pressure. Circulation 2007; DOI: 10.1161/CIRCULATIONAHA.106.661140. Available at: http://www.theheart.org/viewDocument.do?document=http%3A%2F%2Fwww.circulationaha.org.
Erlangen, Germany - A study billed as the first rigorous, randomized trial in the West to test acupuncture against a sham needle technique to treat hypertension suggests that, performed properly, acupuncture may produce blood-pressure changes on a par with monotherapy in mild to moderate hypertension.
"It's certainly not like a wonder drug; it's not a massive effect, but it's a clear effect," lead investigator Dr Frank A Flachskampf (Universitätsklinikum Erlangen, Germany) told heartwire.
Smaller randomized trials have been performed in China, with mixed results, while one randomized study in the West found no difference in blood-pressure lowering between traditional Chinese acupuncture, standardized acupuncture, and a sham procedure, the authors note. This earlier study did not use ambulatory blood-pressure measurements, believed to be superior to office-based measurements.
Results of their study are published online June 4, 2007 in Circulation.
Needlework
For the study, 160 outpatients with uncomplicated, mild to moderate hypertension were randomized to six weeks of acupuncture performed by Chinese medicine practitioners, trained in China, or to a sham procedure. In both arms, patients underwent 22 sessions, each 30 minutes in length. By the end of the six weeks, 24-hour ambulatory systolic and diastolic blood pressures were significantly reduced from baseline in the acupuncture-treated patients (5.4 mm Hg and 3.0 mm Hg, respectively), and this change was also significantly different from values in the sham-treated patients, in whom no meaningful changes were seen.
After three and six months, however, the blood-pressure reductions disappeared, leading investigators to conclude that ongoing acupuncture treatments would be required to maintain the blood-pressure reductions.
"The main finding is that for the first time in a reasonably sized but still relatively small randomized study, this establishes beyond a reasonable doubt that acupuncture lowers blood pressure," Flachskampf commented. "It's a modest but undeniable effect on both systolic and diastolic blood pressure."
The extent of the blood-pressure reductions are comparable to those seen with ACE-inhibitor monotherapy or aggressive lifestyle changes, including radical salt restrictions, he added.
A "demanding" alternative to drugs
Flachskampf had some caveats, acknowledging that the regular acupuncture sessions used in the study represent a significant time investment: each acupuncture session lasted 30 minutes—not including transportation and administrative time—and took place several times a week. The study subjects were also reasonably healthy, with no other major risk factors and with only mild to moderate hypertension.
"This is clearly something that would probably not work as well with very sick people or people with blood pressure at dangerous levels," he said. "We cannot easily extrapolate to people, for example, with complicated hypertension who have had a myocardial infarction."
Flachskampf believes, however, that acupuncture likely represents an attractive option in specific patients, particularly those averse to taking medical therapy who are open to so-called "alternative" medicine.
"This is probably only for people who somehow relate to this spiritually, who say I am profoundly against taking drugs and I'm very fond of Oriental wisdom or things like that," Flachskampf told heartwire. "I don't want to make a joke about this, but this certainly needs more compliance than taking two or three pills a day. It's much more demanding."
Unlike drugs, acupuncture appeared to have few or no side effects, although two people complained that the needles were painful. "Clearly, many millions of Chinese get acupuncture without any major problems so I think this is really a minor point," Flachskampf observed.
Source:
Flachskampf FA, Gallasch J, Gefeller O, et al. Randomized trial of acupuncture to lower blood pressure. Circulation 2007; DOI: 10.1161/CIRCULATIONAHA.106.661140. Available at: http://www.theheart.org/viewDocument.do?document=http%3A%2F%2Fwww.circulationaha.org.
Thursday, June 7, 2007
FDA & GLITAZONES (AVANDIA and ACTOS)
FDA Asks for Black-Box Warning on Heart Failure Risk with Glitazones
In Congressional testimony yesterday, the FDA commissioner revealed that the agency has requested that the manufacturers of rosiglitazone (Avandia) and pioglitazone (Actos) add black-box warnings about the risk for heart failure with these drugs.
The commissioner indicated that the request was made because although the drugs currently carry warnings about potential heart failure, they are still sometimes prescribed to patients with this condition.
The request was only made public yesterday but was made to the companies on May 23, a couple of days after the publication of a meta-analysis that raised questions about the potential risk for heart attacks with rosiglitazone. The manufacturers have indicated that they are in negotiations with the agency over the new warnings.
Link: New York Times story (One-time registration required)
Link: Wall Street Journal story (Subscription required)
Link: Physician's First Watch coverage of interim analysis (Free)
Published in Physician's First Watch June 7, 2007
In Congressional testimony yesterday, the FDA commissioner revealed that the agency has requested that the manufacturers of rosiglitazone (Avandia) and pioglitazone (Actos) add black-box warnings about the risk for heart failure with these drugs.
The commissioner indicated that the request was made because although the drugs currently carry warnings about potential heart failure, they are still sometimes prescribed to patients with this condition.
The request was only made public yesterday but was made to the companies on May 23, a couple of days after the publication of a meta-analysis that raised questions about the potential risk for heart attacks with rosiglitazone. The manufacturers have indicated that they are in negotiations with the agency over the new warnings.
Link: New York Times story (One-time registration required)
Link: Wall Street Journal story (Subscription required)
Link: Physician's First Watch coverage of interim analysis (Free)
Published in Physician's First Watch June 7, 2007
Cardiac Mortality Drop Attributed to Therapies and Risk Factor Reductions
Cardiac Mortality Drop Attributed to Therapies and Risk Factor Reductions
By Neil Osterweil, Senior Associate Editor, MedPage TodayReviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco June 06, 2007
ATLANTA, June 6 -- Credit for the near halving of the rate of coronary disease deaths in the U.S, from 1980 to 2000, belongs equally to reductions in risk factors and to the rise of evidence-based therapies, found CDC and British researchers.
There were 341,745 fewer deaths from coronary heart disease in 2000 than in 1980, and about 47% of that decline can be attributed to primary and secondary medical therapies and interventions, they reported in the June 7 issue of the New England Journal of Medicine.
Reductions in risk factors such as smoking, high cholesterol, hypertension and inactivity get the nod for an additional 44% of the drop in coronary heart disease mortality, according to Earl S. Ford, M.D., M.P.H., of the National Center for Chronic Disease Prevention and Health Promotion, and colleagues.
But they also found that two major factors prevented the decreases in deaths from being even greater.
Our analysis estimated that increases in the body-mass index accounted overall for about 26,000 additional deaths from coronary heart disease in 2000, and increases in the prevalence of diabetes for about 33,500 additional deaths; both figures are consistent with the results of other recent studies they wrote. "Efforts to address these two risk factors should therefore receive particular attention in future measures to improve the public health."
The investigators used a previously validated statistical model called IMPACT to analyze the relative contributions of risk factor reduction, medical therapies, and interventions such as coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty to the decline in coronary disease-related deaths. The analyses were conducted at the University of Liverpool in England.
The difference between the expected and actual number of deaths from coronary heart disease in 2000 versus 1980 was distributed proportionally among the various treatments and risk factors included in the analyses.
They employed primarily data sources that were specific to the U.S. population, using the most up-to-date, least biased, and most representative sources whenever possible.
They found that the age-adjusted death rate for coronary heart disease among men fell from 542.9 deaths per 100,000 in 1980 to 266.8 per 100,000 in 2000. Among women, the rate fell from 263.3 per 100,000 in 1980 to 134.4 deaths per 100,000 in 2000. The total difference in observed vs. expected deaths in 2000 was 341,745.
About 47% of the decrease (159,330 fewer deaths) was attributed to treatments as follows:
Secondary preventive therapies after myocardial infarction or revascularization, 11%,
Initial treatments for acute myocardial infarction or unstable angina 10%,
Treatments for heart failure, 9%,
Revascularization for chronic angina, 5%,
Other therapies 12%.
In additional 44% of the drop could be attributed to the following changes in risk factors (numbers represent percentage of total reduction, and overlap):
Reductions in total cholesterol, 24%,
Decrease in systolic blood pressure, 20%,
Decline in smoking prevalence, 12%,
Reduction in physical inactivity, 5%.
Progress in risk factor reductions was partially offset, however, by an 8% increase in body-mass index over the two decades, by a 10% rise in the prevalence of diabetes, the authors noted.
"Irrespective of the assumptions used, we found that the largest contributions from medical therapies consistently came from secondary prevention, followed by treatments for acute coronary syndromes, then heart failure," they wrote. "Revascularization by means of CABG or angioplasty for stable or unstable disease together accounted for approximately 7% of the overall drop in deaths from coronary heart disease, a finding that is consistent with the results of previous studies in the United States and elsewhere."
They noted that possible study limitations included the use of data from various sources, including some studies that might have been limited by ethnic, geographic, or selections biases. They also noted that most of varying quality o and the averaging of interactions across broad groups, although the analyses were limited only to reductions in deaths, and did not include quality-of-life measures.
Funding source for the study was not specified. The authors reported that they had no conflicts of interest.
Primary source: New England Journal of Medicine
Source reference:
Ford ES et al.
Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000. N Engl J Med 2007;356:2388-98.
By Neil Osterweil, Senior Associate Editor, MedPage TodayReviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco June 06, 2007
ATLANTA, June 6 -- Credit for the near halving of the rate of coronary disease deaths in the U.S, from 1980 to 2000, belongs equally to reductions in risk factors and to the rise of evidence-based therapies, found CDC and British researchers.
There were 341,745 fewer deaths from coronary heart disease in 2000 than in 1980, and about 47% of that decline can be attributed to primary and secondary medical therapies and interventions, they reported in the June 7 issue of the New England Journal of Medicine.
Reductions in risk factors such as smoking, high cholesterol, hypertension and inactivity get the nod for an additional 44% of the drop in coronary heart disease mortality, according to Earl S. Ford, M.D., M.P.H., of the National Center for Chronic Disease Prevention and Health Promotion, and colleagues.
But they also found that two major factors prevented the decreases in deaths from being even greater.
Our analysis estimated that increases in the body-mass index accounted overall for about 26,000 additional deaths from coronary heart disease in 2000, and increases in the prevalence of diabetes for about 33,500 additional deaths; both figures are consistent with the results of other recent studies they wrote. "Efforts to address these two risk factors should therefore receive particular attention in future measures to improve the public health."
The investigators used a previously validated statistical model called IMPACT to analyze the relative contributions of risk factor reduction, medical therapies, and interventions such as coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty to the decline in coronary disease-related deaths. The analyses were conducted at the University of Liverpool in England.
The difference between the expected and actual number of deaths from coronary heart disease in 2000 versus 1980 was distributed proportionally among the various treatments and risk factors included in the analyses.
They employed primarily data sources that were specific to the U.S. population, using the most up-to-date, least biased, and most representative sources whenever possible.
They found that the age-adjusted death rate for coronary heart disease among men fell from 542.9 deaths per 100,000 in 1980 to 266.8 per 100,000 in 2000. Among women, the rate fell from 263.3 per 100,000 in 1980 to 134.4 deaths per 100,000 in 2000. The total difference in observed vs. expected deaths in 2000 was 341,745.
About 47% of the decrease (159,330 fewer deaths) was attributed to treatments as follows:
Secondary preventive therapies after myocardial infarction or revascularization, 11%,
Initial treatments for acute myocardial infarction or unstable angina 10%,
Treatments for heart failure, 9%,
Revascularization for chronic angina, 5%,
Other therapies 12%.
In additional 44% of the drop could be attributed to the following changes in risk factors (numbers represent percentage of total reduction, and overlap):
Reductions in total cholesterol, 24%,
Decrease in systolic blood pressure, 20%,
Decline in smoking prevalence, 12%,
Reduction in physical inactivity, 5%.
Progress in risk factor reductions was partially offset, however, by an 8% increase in body-mass index over the two decades, by a 10% rise in the prevalence of diabetes, the authors noted.
"Irrespective of the assumptions used, we found that the largest contributions from medical therapies consistently came from secondary prevention, followed by treatments for acute coronary syndromes, then heart failure," they wrote. "Revascularization by means of CABG or angioplasty for stable or unstable disease together accounted for approximately 7% of the overall drop in deaths from coronary heart disease, a finding that is consistent with the results of previous studies in the United States and elsewhere."
They noted that possible study limitations included the use of data from various sources, including some studies that might have been limited by ethnic, geographic, or selections biases. They also noted that most of varying quality o and the averaging of interactions across broad groups, although the analyses were limited only to reductions in deaths, and did not include quality-of-life measures.
Funding source for the study was not specified. The authors reported that they had no conflicts of interest.
Primary source: New England Journal of Medicine
Source reference:
Ford ES et al.
Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000. N Engl J Med 2007;356:2388-98.
Wednesday, June 6, 2007
Peripheral Artrial Disease - P.A.D.
Peripheral Arterial Disease (P.A.D.)
Chart - PDF
http://www.acc.org/qualityandscience/clinical/topic/PAD%20Wall%20Chart%20Version%20Final.pdf
Chart - PDF
http://www.acc.org/qualityandscience/clinical/topic/PAD%20Wall%20Chart%20Version%20Final.pdf
Secondhand Smoke Causes Endothelial Dysfunction in Children
Secondhand Smoke Causes Endothelial Dysfunction in Children
from Heartwire — a professional news service of WebMD
June 6, 2007 — Children as young as 11 develop endothelial dysfunction in response to secondhand smoke, in a dose-dependent fashion, even when exposure is minimal, a new study suggests. The study adds to other evidence demonstrating the harmful effects of passive smoking in teenagers and adults. Dr Katariina Kallio (University of Turku, Turku, Finland) and colleagues report the results of their study in a Rapid Access issue of Circulation, June 4, 2007.
"Because endothelial dysfunction related to passive smoking may be only partially reversible after cessation of the exposure, the present data strongly emphasize the importance of implementing smoke-free environments for children at home and in public places," the authors write.
Study Highlites:
Families of 5-month-old infants were invited to participate in this prospective study from Finland. Subjects were randomized to receive education regarding cardiovascular risk factors in childhood or no intervention (control).
Serum cotinine levels were evaluated annually beginning at the age of 8 years, and flow-mediated vasodilatory responses were measured with ultrasonography of the brachial artery at the age of 11 years.
The main study outcome was the relationship between serum cotinine levels and endothelial function. To interpret this relationship, children were stratified into the following levels of cotinine: none, low (0.2 - 1.6 ng/mL), and top decile (1.7 ng/mL or greater). The main study result was adjusted for other cardiovascular risk factors, including serum lipid and high-sensitivity C-reactive protein levels.
402 (73% of the study cohort) children had ultrasound and cotinine data available for analysis. 57% of the children had undetectable levels of cotinine, whereas 33% and 10% of subjects fit into the low- and top-decile cotinine groups, respectively.
No child reported active smoking. 16% of mothers and 25% of fathers smoked.
There was no significant trend across cotinine groups in terms of body mass index, blood pressure, lipid levels, or C-reactive protein values.
Peak endothelium-dependent dilation fell as cotinine levels increased (9.10% in the no-cotinine group vs 8.57% and 7.73% in the low- and top-decile cotinine groups, respectively). This difference was significant after multivariate analysis. Serum cotinine level was also inversely associated with total dilation response.
Cotinine levels had no effect on brachial diameter at baseline, increase in blood flow after cuff release, or endothelium-independent dilation after administration of sublingual nitrate.
When the authors limited their analysis to only children with 4 cotinine values measured between the ages of 8 and 11 years, the relationship between higher cotinine concentrations and impaired endothelial function was even stronger.
Higher levels of low-density lipoprotein cholesterol also impaired flow-mediated dilation, but C-reactive protein levels did not significantly affect this outcome.
Pearls for Practice:
Both active and passive smoking can reduce levels of intra-arterial nitric oxide and impair endothelial function and as little as 30 minutes of passive smoke exposure can induce changes in coronary flow velocity reserve.
The current study demonstrates that exposure to environmental tobacco smoke impairs endothelium-dependent dilation in children.
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