In preliminary results from a randomized controlled trial in Botswana, men and women who got an anti-HIV medication saw their relative risk of HIV reduced by 62.6% compared with those who got placebo, according to Michael Thigpen, MD, of the CDC.

The medication — a single-pill combination of tenofovir and emtricitabine (Truvada) — was also safe and well-tolerated, Thigpen said at the 2011 conference of the International AIDS Society.

The finding comes after an earlier study of so-called pre-exposure prophylaxis, or PrEP — this one among men who have sex with men — showed the same medication reduced the risk of infection.
Action Points
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■Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

■Explain that in this study, a pill a day containing a combination of tenofovir and emtricitabine (Truvada) prevented transmission of HIV among heterosexual men and women.

■Note that those receiving the study drugs reported significantly more adverse events than those in the placebo group, a difference driven by increased rates of nausea and vomiting.

And it comes as another study, also presented here, showed a similar result among men and women in so-called discordant couples — those in which one partner has HIV and the other does not.

“This is a really exciting time in HIV prevention,” Thigpen told MedPage Today. There is now “little doubt about the power of anti-retroviral-based HIV prevention strategies,” he added.

The so-called TDF2 study analyzed rates of HIV infection among 1,200 uninfected men and women in Botswana, more than 93% of them single — in contrast to other studies in couples. As in all such trials, participants got a package of services intended to increase their awareness of HIV and reduce their risk of infection, including access to condoms and counselling about safe sex.

After more than two years of follow-up, there were nine HIV infections among those getting the study drug and 24 in the placebo group, yielding an overall protective efficacy of 62.6%, Thigpen said. The result was “strongly significant” at P=0.0133, he said.

The result was even more striking when the researchers restricted their analysis to participants who became infected while they were on the study drug or within 30 days of their last dose, Thigpen said.

In that group, he said, there were four infections in the active group and 19 among those getting placebo, for a protective efficacy rate of 77.9%, which was significant at P=0.0053.

One participant in the drug arm — who had an unrecognized HIV infection at baseline — developed high-level resistance to the study drugs, Thigpen said. One participant on the placebo arm developed low-level resistance, he said.

Those getting the study drugs reported significantly more adverse events (at P=0.019) than those in the placebo group, a difference driven by increased rates of nausea and vomiting — 18.8% versus 7.2% and 11.5% versus 6.8%, respectively.

On the other hand, there were no differences in the number of abnormal laboratory values by treatment group, Thigpen reported.

There were also no differences in treatment adherence, estimated by pill count, or in reported sexual behavior, the researchers found.

The study, along with others presented here, represents an “unprecedented opportunity to expand the toolkit for prevention,” said Gottfried Hirnschall, MD, head of the World Health Organization’s HIV department in Geneva.

Hirnschall said the United Nations agency had wanted to launch new guidelines here on care for discordant couples, but has pulled them back for more work after the two new studies presented here.

And he cautioned there remains “a treatment gap of nine million people” who need HIV therapy but are not getting it.

But Stefano Vella, MD, of Italy’s Istituto Superiore di Sanita and a conference co-chair, said getting treatment to those people is no longer a matter of “humanitarian aid.”

In the light of the recent research, Vella told reporters, “this is a real investment” in slowing and perhaps halting the HIV/AIDS pandemic.

Despite the positive PrEP results, several experts said there is still some concern over the halted FEM-PrEP study, which was testing tenofovir/emtricitabine as PrEP in women in three African countries.

The study was stopped earlier this year when an interim analysis revealed similar numbers of HIV infection in both the placebo and drug arms, with little likelihood that would change.

“It’s important not to forget about that and consider it a fluke,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. He called for further “serious studies” to see why the FEM-PrEP trial did not work as well as others.

The study was supported by the CDC and the National Institutes of Health.

The meeting comes after two years of “significant biomedical discoveries,” said Elly Katabira, MD, of Uganda’s Makarere University and president of the society.

Those discoveries include the recent proof that triple-drug therapy can prevent transmission of HIV, as well as hints of a successful vaccine and a first report of a working microbicide that can be used by women to prevent infection, Katabira told reporters as the conference opened.

Details of those and other findings — many to be presented here — may one day be seen “as important as the antiretroviral breakthroughs of the 1990s,” Katabira said — breakthroughs that changed HIV infection from a death sentence to a chronic disease.

But Katabira and others cautioned that scientific “proof alone is not enough” to turn the tide of the pandemic, which has claimed some 30 million lives in the past three decades.

Instead, they said, the goal now should be to mobilize both the public and private sector to translate the science into concrete action. The main focus should be to ensure widespread access to the medications that not only save lives but — the “proof” Katabira spoke of — can prevent the virus from being transmitted.

Currently, about half of the 33.3 million people with HIV around the world are not getting treatment, according to the United Nations, and deploying anti-HIV drugs to prevent transmission would put increased pressure on the drug supply.

“We are at a game-changing moment in the story of HIV/AIDS,” said Michel Sidibe, executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), largely because of the recent science.

But, he told MedPage Today, changing the game will require convincing governments to start thinking about “the end of this epidemic,” instead of stopgap measures. And, he added, it will require more research — this time on ways to cut costs and improve delivery of drugs and services.

The chances of stopping the pandemic “just got tremendously better,” argued Chris Beyrer, MD, of Johns Hopkins University in Baltimore. “But we have now an enormous operations research challenge agenda in rolling out this science and getting people access to it.”

There is “tremendous optimism in the field,” he told MedPage Today, “that we can prevent new infections and save a large number of lives.”

That optimism was boosted last week, when Gilead Sciences, of Foster City, Calif., agreed to allow four of its anti-HIV drugs to be copied generically, probably lowering their prices in the developing world.

This meeting will be the first to get full details on a major study that showed that treating the infected member of a couple — well before it is clinically indicated — dramatically reduces the risk of transmitting the virus.

Researchers will also present the final analysis of the blinded part of a study of pre-exposure prophylaxis among high-risk men who have sex with men, a trial that showed a 44% reduction in the risk of acquiring the virus for men who took a daily dose of an antiretroviral drug.

And details of two more studies among heterosexuals are expected to reinforce the lesson that anti-retroviral drugs can prevent transmission, as well as prolong life for people with HIV infection.

The conference also includes:
•Early data on some new antiretroviral drugs.
•Studies that show that rates of virological failure while on triple drug therapy have been falling both in the developed world and — perhaps more importantly — in some parts of the developing world.

Several studies have found no evidence of benefit for recommending such levels of hydration, although bottled water companies would have consumers believe otherwise, argues Margaret McCartney, MD, of Glasgow, Scotland, in a commentary in BMJ.

“There are many organizations with vested interests who would like to tell doctors and patients what to do,” McCartney wrote. “We should just say no.”

The recommendation to drink eight glasses of water a day (at eight ounces each) has become a standard for healthy hydration. It’s the level recommended by Britain’s National Health Service, and the U.S. Institute of Medicine (IOM) in 2004 found that “adequately hydrated” women consumed 91 ounces of water a day, and men had 125 ounces — almost 16 glasses.

However, those amounts can come from coffee, tea, milk, soda, juice, fruits, vegetables and other juicy foods, and ultimately the IOM recommends that thirst should be a patient’s guide to intake.

But in a brief literature review, McCartney found several studies showing no clear evidence of benefit for such levels of hydration.

A 2002 study by Heinz Valtin, MD, published in the American Journal of Physiology, for instance, concluded that there’s “no scientific evidence that we need to drink that much,” and those levels may even be harmful, resulting in hyponatremia and exposure to pollutants.

A 2008 editorial in the Journal of the American Society of Nephrology noted that while there’s no clear evidence of benefit, there’s “no clear evidence of lack of benefit” either — thus, a “lack of evidence in general.”

Studies cited by hydration advocacy groups such as Hydration for Health, which is sponsored and created by the French food giant Danone (maker of Evian, Volvic, and Badoit bottled waters), are limited, McCartney says — they’re either retrospective studies with methodological limitations or based on low-quality guideline recommendations.

More recently, the organization promoted a claim that hydration prevents chronic kidney disease, but McCartney argued that is supported merely by one cross-sectional study recently published in Nephrology.

“Examination of the evidence presented by Danone shows it to be weak and subject to selection bias,” she wrote. “Danone says we need ‘informed choices,’ but its evidence does not support its call to action.”

Stanley Goldfarb, MD, of the University of Pennsylvania, who was interviewed by McCartney, told ABC News and MedPage Today that “there’s just no evidence for keeping yourself hydrated above and beyond the need to avoid thirst.”

“There really is no evidence that it makes you perform better, it doesn’t reduce appetite, it doesn’t lead to long-term weight loss, it can’t possibly improve your complexion,” he said. “But many physicians still recommend it, I think, because it really can’t hurt you.”

Randy Wexler, MD, professor of family medicine at Ohio State University, said he tells patients simply to remain adequately hydrated, via any means necessary: “There’s no evidence I am aware of that says it must be water.”

Yet he tells those prone to dehydration, especially the elderly, to avoid caffeinated beverages that can cause over-diuresis.

And because he says all patients have different “thirst sensors,” he advises that they monitor the color of their urine to gauge their dehydration instead.

“The more clear the urine, the better the hydration,” he said in an email to MedPage Today and ABC News. “The darker, more yellow the urine, the more dehydrated one is.”

Presenting a cost-utility analysis and other findings from research conducted through the NIH-sponsored Diabetes Prevention Program (DPP) at a press briefing at the ADA 71st Annual Scientific Sessions, William H. Herman, MD, MPH, reported that lifestyle intervention and metformin treatment are cost-effective methods for preventing type 2 diabetes (T2D) in patients at high risk.

The DPP was a randomized controlled trial that followed 3,234 high-risk participants assigned to one of three groups. The lifestyle intervention group received training in diet, exercise, and behavior modification. The metformin group received 850 mg/bid, and a third group received placebo. The metformin and placebo groups also received information about diet and exercise, but did not receive motivational counseling. After seven years of follow up, participants were given the option of participating in a diabetic prevention outcomes study. Together, researchers collected data spanning 10 years.

“A cost-utility analysis was conducted in part because of skepticism in the community that diabetes interventions were too expensive,” said Herman. The basic idea of the analysis was to determine costs associated with improving quality of life. In cost-utility analyses, the health outcome is described in terms of quality-adjusted life-years (QALY’s), which measure length of life adjusted for quality of life. A “health utility score” is assigned to quality of life that reflects the desirability of the outcome based on the societal preference for various health states. For example, perfect health would be rated 1.0 and death would be rated 0.0. A year of life for someone with diabetes, for example, may have a health utility score of 0.7.

Quality of life in study participants was improved with both lifestyle and metformin interventions compared to placebo. However, the costs (eg, direct medical) associated with the lifestyle intervention were $1500 more per participant compared to placebo over the 10 years of the study. This can be translated to a cost of $12,000 per QALY gained. In contrast, total direct costs associated with metformin were $30 less than placebo. Although the lifestyle intervention was associated with a higher cost, “it was ultimately more cost effective than placebo because the latter resulted in higher costs later on,” explained Herman. Specifically, the lifestyle intervention reduced the cost of medical care over 10 years by $2600. Metformin reduced costs by $1700.

In addition to improving quality of life, both interventions resulted in a reduction in development of T2D. Lifestyle intervention resulted in a 58% reduction and metformin resulted in a 31% reduction. “It is likely that the lifestyle intervention over a longer timeframe will have additional benefits in terms of lipid levels, cardiovascular fitness, quality of life, and other factors,” said Herman.

The goal is not necessarily to avoid paying for interventions, but rather determining “is this a good investment, a good value for your money?” When considering the improvements in quality of life and reductions in development of diabetes, Herman is convinced this is the case. He also pointed out that the “investment” of lifestyle intervention is on par with other widely accepted interventions such as using beta blockers after myocardial infarction, antihypertensive therapy, and statins for secondary prevention of cardiovascular disease. Herman said that he hopes to see changes in health care policies that encourage fewer costs associated with interventions. Regardless, both metformin and lifestyle interventions ultimately saved money and improved quality of life, “so they should both be widely accepted,” Herman said.

Use of preventive medication ranged from 25% for ACE inhibitors to 36% for aspirin. Assuming a PAD prevalence of 7.1 million adults, the proportion not using secondary-prevention drugs ranged from 4.5 million to 5.4 million, depending on the drug.

After adjustment for multiple confounders, PAD doubled the hazard for all-cause mortality compared with individuals without the condition. In people with PAD but not cardiovascular disease, use of multiple preventive medications reduced the mortality hazard by 65%, as reported online in Circulation.

“These observational findings highlight the critical need for a large-scale clinical trial to determine whether the implementation of secondary prevention therapies in high-risk individuals identified by ankle-brachial index screening as having PAD can reduce mortality and cardiovascular events,” Reena L. Pande, MD, of Harvard and Brigham & Women’s Hospital in Boston, and co-authors concluded.

A manifestation of systemic atherosclerosis, PAD significantly increases the risk of cardiovascular events regardless of symptoms. Several studies have shown that PAD remains under recognized and under treated. However, the proportion of PAD patients not receiving preventive therapies remains unknown, the authors wrote in the introduction to their findings.

In an effort to quantify the use of medications by patients with PAD, Pande and colleagues queried the National Health and Nutrition Evaluation Survey (NHANES).

During 1999 to 2004, NHANES participants 40 and older had lower-extremity evaluations that included measurement of the ankle-brachial index (ABI). A value ≤0.90 was considered diagnostic for PAD.

The authors examined use of guideline-recommended therapies for secondary prevention, including antiplatelet therapy, statins, and ACE inhibitors and ARBs.

Follow-up data were available through 2006. The primary endpoint was all-cause mortality.

The analysis included 7,458 NHANES participants. The study population had a mean age of 68, and women accounted for almost 60% of the cohort.

ABI values showed that 647 of the patients had PAD, including 196 participants who also had cardiovascular disease (CVD).

The authors reported that 68% of participants with PAD had LDL values >100 mg/dL, and 46% had systolic blood pressure >140 mm Hg. Nonetheless, 69.5% of the PAD group were not taking statins, and 75.1% were not taking an ACE inhibitor or ARB. Additionally, 64% of the group was not taking aspirin, and 61% of the PAD patients were taking no antiplatelet agents.

Separate analyses of patients with and without concomitant CVD showed that fewer patients with PAD were not using statins (42.5%), ACE inhibitors or ARBs (62.5%), aspirin (44.1%), or any antiplatelet therapy (34.2%).

PAD patients without CVD had the lowest rates of use for all of the medications: statins, 18.3%; ACE inhibitor/ARB, 20.8%; aspirin, 27%; and any antiplatelet therapy, 27.4%.

Extrapolating the PAD prevalence among the NHANES participants (5.9%) to the general population, the authors estimated that 7.1 million adults in the U.S. have PAD. An estimated five million patients do not take statins, 5.4 million do not take an ACE inhibitor or ARB, and 4.5 million do not use aspirin.

During a mean follow-up of 4.4 years, NHANES participants with PAD had a 22.6% mortality, compared with 5.0% for participants without PAD.

After adjustment for age, sex, and race, the authors found that PAD conferred a mortality hazard of 2.4 compared with no PAD (P<0.0001). Even after excluding patients who had PAD and CVD, PAD doubled the mortality risk (HR 1.9, P=0.001).

Among patients with PAD but not CVD, use of multiple preventive therapies reduced the mortality hazard by 65% compared with patients using none of the medications (HR 0.35, P=0.02) after adjustment for all confounders.

However the sample included only 450 individuals with PAD who did not have established cardiovascular disease, which limited the ability to observe effects of individual treatment. Also, it was not know if a new diagnosis of PAD altered medical management of patients. Finally, NHANES relies on self-reporting of diagnoses so diagnosis of cardiovascular disease was not independently confirmed.

Despite being judged at low cardiovascular event risk by the widely-used Framingham risk score, ultrasound imaging of a small cohort of women (most obese or with metabolic syndrome) revealed abnormalities in the carotid artery, in left ventricular or left atrial size, or in diastolic function, Danya L. Dinwoodey, MD, of Massachusetts General Hospital, Boston, and colleagues reported here at the American Society of Echocardiography meeting.

These results suggest that traditional risk factors may not be enough to guide preventive treatment and counseling for these women, said Dinwoodey.

“These things we were looking at have been shown in previous studies to confer poor cardiovascular outcomes,” Dinwoodey said in an interview with MedPage Today. “Just by doing a simple ultrasound we’re finding that they are actually much higher risk for cardiovascular events.”

The researchers recommended screening women diagnosed with obesity or metabolic syndrome using selected ultrasound imaging to help further risk-stratify such patients.

Full echocardiograms may be too expensive for primary prevention screening, Dinwoodey cautioned, but a couple of ultrasound views of key areas of the heart, along with measuring carotid intima media thickness (IMT), may be feasible for clinical use.

The role of echocardiography among other screening modalities still needs to be determined, Dinwoodey added.

“There are a lot of potential candidates for better risk stratifying,” she told MedPage Today. “At this point, it’s not clear what the best way to do this is … but it’s clear that what’s currently available is not working. It’s not accurately predicting a woman’s true risk for cardiovascular disease.”

To search for better ways to assess risk, Dinwoodey and her team analyzed baseline data from the Heart Awareness and Primary Prevention in Your Neighborhood (HAPPY Heart) trial, designed as a lifestyle intervention trial.

In the study cohort, the researchers analyzed complete ultrasound data for 43 asymptomatic, low-income Caucasian or Hispanic women (mean age 50.7) who had at least two traditional cardiac risk factors but a normal left ventricular ejection fraction.

Among the women, 67% were obese and 74% had metabolic syndrome. Yet all had a Framingham risk score predicting less than a 10% cardiovascular risk over 10 years.

While 67% of the women had an abnormal ultrasound finding at baseline, among the 32 women with metabolic syndrome, 75% had an abnormal ultrasound, and 79% of the 29 obese women had abnormal ultrasounds.

The most common ultrasound abnormality was elevated IMT — defined as over 75% of predicted for age and race or at least 1.2 mm of carotid plaque. It showed problems in 37% of women overall and in 45% of the obese women and 41% of those with metabolic syndrome.

Diastolic dysfunction appeared in 37% overall, with a slightly higher rate in obese women (38%) and metabolic syndrome cases (41%).

Echocardiography showed an enlarged left atrial volume index of more than 34 mL/m2 in 30% of women overall (38% in obese women and 34% in metabolic syndrome) but none had elevated left ventricular wall mass of greater than 89 g/m2.

Although the diagnosis of metabolic syndrome requires at least three of the five components of the disorder — abdominal obesity, insulin resistance, low HDL cholesterol, high triglycerides, and high blood pressure — women with more components appeared to carry greater risk of an abnormal echocardiography finding.

Ultrasound imaging may have a side benefit in helping women recognize the need for risk reduction, Dinwoodey said. She explained that in the intervention portion of the study she had seen women take charge of their risk factors and prepare to make healthy lifestyle changes after seeing the state of their carotid arteries and heart.

At the same time, Dinwoodey cautioned that the pilot study was limited by its small sample size.

Overall, 38% of such patients at a large urban medical center had coronary artery disease, according to Deepak Gupta, MD, of Northwestern University in Chicago.

Echocardiography revealed poorer left and right ventricular function and increased filling pressures, he reported at the American Society of Echocardiography meeting here.

In addition, patients with coronary artery disease had a greater likelihood of being hospitalized for heart failure and of dying during 18 months of follow-up (HR 1.7 and 3.2, respectively).

“Together, these data suggest that patients with [coronary artery disease] represent a discrete pathophysiologic subset within [heart failure with preserved ejection fraction],” Gupta said.

Although the patients with coronary artery disease were taking more medications specifically for the condition than the other patients with heart failure with preserved ejection fraction, Gupta and his colleagues have not yet looked at whether those treatments impact clinical outcomes.

Numerous previous studies have shown that coronary artery disease is common in patients with heart failure with preserved ejection fraction, with prevalence ranging from 15% to 65%.

But those studies were limited, Gupta said, in that they preceded contemporary management of coronary disease; lacked systematic evaluation and definition of coronary disease; used various definitions for heart failure with preserved ejection fraction; and had variable use of echocardiography.

None of the studies, however, has directly compared echocardiographic characteristics of those patients with and without coronary disease, Gupta said.

So he and his colleagues conducted a prospective, observational study of 354 patients who had been hospitalized previously for heart failure, and who had an ejection fraction greater than 50% (the average was 61%).

Patients with prior heart failure with an ejection fraction lower than 40%, constrictive pericarditis, severe valvular disease, or prior cardiac transplant were excluded.

The researchers diagnosed coronary artery disease using a predefined algorithm that included medical history, angiography, and stress testing (for those who could not undergo angiography).

The 38% of patients who had coronary artery disease were older (mean 70 versus 62), more likely to be male, and more likely to have comorbidities, including diabetes, hypertension, dyslipidemia, and chronic kidney disease (P<0.05 for all). They were less likely to be obese, however.

Pulse pressure was higher in those with coronary disease (68 versus 62 mm Hg, P<0.003).

In terms of the echocardiographic findings, there was no difference in left ventricular ejection fraction and diastolic function grade, but there were higher filling pressures — indicated by higher septal and lateral E/E’ — and reduced systolic S’ and diastolic A’ velocities in patients with coronary disease (P<0.05 for all).

Those with coronary disease also had lower right ventricular function as shown by reduced TAPSE or tricuspid annular plane systolic excursion, which is a measure of right ventricular ejection fraction and right ventricular fractional area change (P<0.01 for both).

In a multivariate analysis, coronary artery disease was independently associated with reduced S’ velocity, TAPSE, right ventricular fractional area change, and higher septal E/E’ (P<0.05 for all).

Coronary disease was also associated with significantly higher rates of heart failure hospitalization (34% versus 22%) and all-cause death (21% versus 10%) during follow-up (P<0.05 for both).

Gupta acknowledged some limitations of the study, including the use of patients from a single center; the fact that not all of the patients underwent coronary angiography; and the use of patients with a prior hospitalization for heart failure.

Although that excluded some ambulatory patients, Gupta said, the goal was to include the highest-risk patients.

Using this newer imaging technique, an E/E’ ratio higher than 30 was associated with an increased risk of all-cause death through nearly two years of follow-up (HR 1.82, 95% CI 1.23 to 2.69), according to Sirikarn Napan, MD, of Howard University Hospital in Washington, D.C.

“The E/E’ ratio obtained by this novel method may be a useful addition to existing risk stratification models for risk prediction in patients with acute coronary syndromes,” Napan said at the American Society of Echocardiography meeting here.

Although the E/E’ ratio is a well-validated measure of diastolic function, it is typically assessed with tissue Doppler imaging.

In the current study, the researchers used speckle-tracking echocardiography, which has some advantages, according to Napan. Those include the fact that it is angle independent and can be performed any time offline after the echocardiographic images have been obtained.

Still, there is little data about the prognostic importance of diastolic function in patients with acute coronary syndromes.

So Napan and her colleagues retrospectively studied 246 patients who were admitted to Howard University Hospital for unstable angina, ST-segment elevation MI (STEMI), or non-STEMI and had an echocardiogram performed within 24 hours of admission.

The researchers excluded patients with moderate-to-severe mitral regurgitation or significant mitral annular sclerosis and those who had a history of postoperative acute coronary syndromes, acute MI in the year before admission, and any cardiac procedure in the 90 days before admission.

The speckle-tracking software analyzed the echocardiographic images and provided peak early and late diastolic mitral annular velocities (E’ and A’, respectively) and systolic mitral annular velocities (S’) by averaging values from all four regions.

Pulsed-wave Doppler provided peak early diastolic mitral inflow velocity (E).

The average age of the patients was 62. Most (56.1%) presented with unstable angina, 35.4% had a non-STEMI, and 8.5% had a STEMI.

Overall, 42.7% underwent coronary angiography during admission — 20.3% had a percutaneous coronary intervention and 2% underwent CABG. Follow-up lasted a median of 21 months.

In a multivariate analysis, E/E’ ratio was associated with an increased risk of all-cause death, as was E’/A’ ratio (HR 1.23, 95% CI 1.06 to 1.43). E’ and A’ were negative predictors of death (HRs 0.78 and 0.73, respectively, P<0.05 for both).

The cutoff value of the E/E’ ratio determined to be discriminatory for risk of death was 30, and 23% of patients had a ratio higher than that.

After adjustment for clinical predictors of mortality and conventional echocardiographic parameters, an E/E’ ratio greater than 30 remained predictive of all-cause mortality (HR 1.91, 95% CI 1.09 to 3.32).

Older patients, those with higher creatinine levels, and those with increased posterior wall thickness were significantly more likely to have an E/E’ ratio greater than 30. Males and those with higher left ventricular ejection fractions were less likely to have a ratio that high (P<0.05 for all).

Napan noted some limitations of the study, including the lack of repeated echocardiograms, the lack of information on other outcomes like heart failure and recurrent MI, and lack of a comparison of E/E’ calculated by speckle-tracking echocardiography and by tissue Doppler imaging.

There have been two studies comparing the two techniques, although they yielded conflicting results, she said. One found a good correlation between the two and the other found a poor correlation.

Napan and her colleagues are currently performing a study to compare E/E’ measured with speckle-tracking echocardiography with that obtained by invasive measurement by cardiac catheterization.

In a future study, Napan said she would like to explore the prognostic value of E/E’ in a prospective fashion using both speckle-tracking echocardiography and tissue Doppler imaging to find out which technique is better.

Napan reported that she had no

At a high-volume transplant center, the only echocardiographic features associated with worse perioperative outcomes after transplantation were left ventricular end-systolic dimension and left atrial enlargement (P<0.05 for both), according to Matthew Harinstein, MD, of the University of Pittsburgh.

Presence of an intracardiac shunt or pulmonary hypertension — both of which are used as contraindications to transplantation in some centers — were not associated with the inhospital rate of major adverse cardiac events, which included stroke, heart failure, MI, and cardiovascular mortality, he reported at the American Society of Echocardiography meeting here.

Importantly, he added in an interview, presence of an intracardiac shunt was not associated with an increased risk of stroke either. Clinicians in some centers have feared that the influx of fluid to the heart after a new liver is transplanted would increase the risk of stroke in patients with a shunt.

“This is an important finding for patients because that way, at centers that maybe are more selective as to whom they allow to be transplanted because they’re trying to make sure they get the optimal candidate, they don’t exclude a patient who has that or they don’t have them getting an unnecessary procedure to have that shunt closed prior to being a candidate for surgery,” Harinstein said.

With improved therapies and survival for patients with end-stage liver disease, candidates for transplantation are growing older and the presence of multiple comorbidities is common. But there has not been a lot of research on how echocardiograms might be used to predict cardiovascular events in patients going in for a transplant.

So Harinstein and his colleagues analyzed data from 375 patients (mean age 56; 66% male) with end-stage renal disease who underwent transplantation and had a preoperative transthoracic echocardiogram.

Cardiovascular risk factors were common, including hypertension (39%), diabetes (32%), history of tobacco use (25%), hyperlipidemia (16%), and family history of coronary artery disease (12%). More than half of the patients had two or more of the risk factors.

Overall, the inhospital rate of major adverse cardiac events was 6.4%. There were no strokes.

Although left ventricular end-systolic dimension and left atrial enlargement were predictive of perioperative events, Harinstein said that those features should not be considered contraindications to transplantation, but rather indicators that further evaluation and possibly further treatment are needed before surgery.

“If larger studies show that the events were really that high, then, yes, they could eventually be a contraindication,” he said.

The study also showed that intracardiac shunts and pulmonary hypertension (a pressure greater than 40 mm Hg) should not keep someone off the transplant list, as happens in many centers, particularly lower-volume centers that are more careful about choosing optimal candidates, Harinstein said.

“There may be a lot of good candidates out there who aren’t getting the benefit of liver transplant surgery because we’re excluding them based on these features,” he said.

“This is sort of an untapped area where we don’t know a lot about … how we can prevent cardiovascular complications in these patients,” he said, “so I think looking at how to make them candidates or make them better candidates is critical.”

Of 366 obese patients and 142 normal-weight patients who had a negative stress echocardiogram after presenting with chest pain, none had a major adverse cardiac event through one year, according to Sheldon Litwin, MD, of Georgia Health Sciences University in Augusta.

There has been some uncertainty about the accuracy of stress echocardiography in obese individuals, he said at the American Society of Echocardiography meeting.

He said that these findings indicate that “if we do a stress echo and it’s completely normal, that should be very reassuring, and it should help us to feel that we don’t necessarily need to go on and do additional testing, which has implications for the cost of healthcare and also for that particular patient, and for medical-legal reasons.”

Evaluating chest pain in obese patients presents challenges because of body size and because obesity itself is related to numerous causes of shortness of breath besides coronary artery disease, including sleep apnea, pulmonary hypertension, and general deconditioning, Litwin said.

There are limited data on the best test to use first to investigate the cause of chest discomfort in this patient population.

“The reality is all of our tests are challenged in the severely obese people. I think nuclear [scans], echo, even invasive angiography [are challenging] because of the size of the tables and the vascular access issues,” Litwin said.

These issues with evaluating the obese patient will become even more of a concern in the future as obesity rates continue to increase in the U.S population.

To explore whether stress echocardiography can reliably exclude coronary artery disease in obese individuals, Litwin and his colleagues performed a retrospective chart review of 1,446 patients who underwent stress echocardiography after presenting with chest pain.

After excluding patients who were overweight but not obese (body mass index 25 to 29.9 kg/m2), those with an abnormal echocardiogram, and those lost to follow up, the researchers were left with 366 obese patients and 142 who had a normal BMI (18.5 to 24.9 kg/m2).

The average BMI was 37.3 kg/m2 in the obese group and 22.6 kg/m2 in the normal-weight group. The obese patients had multiple cardiovascular risk factors, and were significantly more likely to have diabetes, hypertension, and complaints of chest pain during the initial evaluation (P<0.05 for all).

Obese patients were slightly older, on average, although the difference did not reach statistical significance (53.2 versus 50.3).

The researchers reviewed records and contacted patients by telephone to determine the rate of major adverse cardiac events, including cardiovascular mortality, myocardial infarction, and cardiac intervention as well as revascularization, in the year following the normal stress echocardiogram.

None of the patients had an event during follow up.

Litwin and his colleagues acknowledged some limitations of the study, including the retrospective design; the dependence on telephone questionnaires for follow up; the possibility of recollection bias; and the exclusion of overweight but not obese patients.

“There’s certainly more work that needs to be done in this field and I think the question of how we evaluate, and how we image obese patients, is one that really looms very large on the horizon for us,” Litwin said.

“And in an era [where] we’re trying to contain costs and trying not to do multiple layered imaging tests, figuring out what the best starting test is in this particular patient population is really, really important,” Litwin said, adding that he would like to see additional prospective, multicenter studies in this population.