CME DIGEST – December 2013


Holiday Heart Syndrome—real or myth?

proactive approach with risk stratification

By Ramon F. Abarquez, Jr. MD, EFACC, FAsCC, FPCP, FPCC, CSPSH
Academician, National Academy of Science and Technology Professor Emeritus, College of Medicine, University of the Philippines Chair, Philippine Medical Association Continuing Medical Education Commission

EACH HOLIDAY SEASON, particularly during the Yuletide long vacation, solicited or not, the health advisory is usually moderation rather than ‘binge’ activities. However, should everyone celebrating the ‘Birth of the Lord’ be over-cautious? Or is there a ‘limited-few’ who are at greater adverse risk? The challenge for physicians is to identify these individuals who are at risk so they could be properly forewarned and adequately treated.

The coming holidays maybe a solemn ceremonial to some or a festive reunion to the majority. But more importantly, reflective opportunities should be primordial. Why? The season may translate into clinically preventable morbidity and mortality consequences.

The “Holiday Heart” syndrome was coined in 1978, to describe patients who had atrial fibrillation following ‘binge alcohol’ drinking. (Glatter, Curr Treat Options Cardiovasc Med. 2012;14(5):529-35)

Is ‘binge drinking’ also prone to an episode of ventricular fibrillation leading to sudden death that may be a random occurrence or weather-related? In a mortality review in Australia, (January 1, 2008 to December 31, 2009) most cases had holiday-related deaths. (Bierton, Forensic Sci Med Pathol. 2012; Oct 12) Usually the ‘at-risk-individual’ is more prone to be the victim. Thus, considerable options for risk stratification with positive action plans can result into opportunities for a progressive quality of life improvement that should be incorporated in any New Year’s ‘must-do’ resolution.

Assessing risk profile

Poor prognosis is related to target organ damage and not to the mere presence of high BP, dyslipidemia, DM, obesity or smoking.”Heart burns” or reflux esophagitis caes, even with medical therapy, are also at risk of sudden death in a retrospective Finnish study. (Rantanen, Am J Gastroenterols.2007;102(2):246-53); and especially among those patients taking domperidone (Prescrire Int. 2012;21(129):183)

CME DIGEST - Holiday Heart Syndrome

Cases with post-prandial bradycardia (Mizumaki,J Cardiovasc Electrophysiol. 2007;18(8):839-44) or hyperglycemia related AF are also at higher risk. (Kato, J Cardiol. 2006;48(5):269-720) particularly among cases with ‘full-stomach’ (Ikeda, J Cardiovasc Electrophysiol. 2006;17(6):602-7)

Diabetic cases with post-prandial reactive hypoglycemia (Brun, Diabetes Metab.2000;26(5):337-51.) can develop AV blocks. (Okamoto, Intern Med. 1997;36(8):579-81) A year after diagnosis of ‘unspecified chest pain’ attributable to cardiac, gastrointestinal, respiratory, psychological or musculoskeletal etiologies and after adjustment for age, sex and number of primary consultations, the odds of an eventual diagnosis of heart failure or coronary heart disease were 4.7 and 14.9 times greater, respectively compared to control, Similarly, the odds of a diagnosis of gastro-esophageal reflux disease (GERD), hiatus hernia or peptic ulcer disease were associated with at least threefold risk more than those with psychological, respiratory and musculoskeletal impression.

More importantly, mortality rate was increased among patients with “unspecified chest pain” during a mean follow-up period of 4 years with 842 of 13 740 (6.12 percent) patients dead in the unspecified chest pain cohort, compared with 710 of 20 000 (3.55 percent) patients in the control cohort. (Ruigomez, Family Practice 2006;23 (2):167-174)

The role of cigarette smoking on cardiac arrhythmia is less clearly defined wherein pro-fibrotic effect of nicotine on myocardial tissue with consequent increased susceptibility to catecholamine could be the mechanism. (D’Alessandro, Eur J Prev Cardiol. 2012;19(3):297-305) More importantly however, after the ‘no-smoking law’ in restaurants and work-place was enforced in Olmstead County, Minnesota, the incidence of acute MI and sudden cardiac death decreased by 33 percent and 17 percent respectively in 18 months despite the persistent prevalence of hypertension, DM, dyslipidemia and obesity. (Hurt, Arch Intern Med.2012;29:1-7) Furthermore, mothers smoking 1-10 and > 10 sticks of cigarettes daily give a 2.93 and 4.36 times more infant sudden death, respectively.

Binge eating, drinking

During holidays with festive moods, binge eating and drinking are widely hypothesized to be related to idiopathic tachyarrhythmias that can lead to sudden death.(Fuenmayor, Int J Cardiol. 1997 ;59(1):101-3.) Dysrrhythmias are considered to be frequently alcohol-related and confirmed by positive screening test for alcoholism. Among 289 patients (aged < 65 years) admitted for supraventricular tachyarrhythmias, 35.3 percent had idiopathic arrhythmia with a known drink related onsettime, specifi cally more often among chronic alcohol abusers. Arrhythmia, independent of the most recent ethanol use, occurred during weekends (47 percent), during weekdays (22 percent; p = 0.040) compared to out-of-hospital population (12 percent; p = 0.002). However, the increased frequency of problem drinkers among patients with weekend-onset idiopathic arrhythmias was only relative since the number of abstainers and non-problem drinkers have decreased. (Kupari, Am J Cardiol. 1991;67(8):718-22) However, even among those with no known cardiac disease, the most frequent tachyarrhythmia is atrial fi brillation and less frequently, but with worse prognosis, is ‘torsades de pointes’ polymorphic ventricular tachycardia. (Treibal, Vnitr Lek.2008;54(4):410-4)

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CME DIGEST – September 2013


Colchicine for acute pericarditis

When added to anti-inflammatory agents, the drug may significantly improve outcomes

PHYSICIANS HAVE ALWAYS used colchicine for gouty arthritis. But this good old drug appears to be also good enough for acute pericarditis.

Actually there have been previous recommendations by experts for the use of colchicine for acute pericarditis, but there was no strong evidence to support it. To help resolve the issue, Imazio M et al. conducted a randomized, double-blind trial of colchicine for acute pericarditis at five tertiary centers in Italy. (N Engl J Med 2013 Sep 1)

CME DIGEST - Colchicine

A total of 240 patients with a first episode of acute pericarditis were randomized to receive colchicine (0.5 mg twice/day for patients weighing >70 kg and 0.5 daily for those weighing =70 kg) or placebo for 3 months. All patients were also given anti-inflammatory agents, mostly aspirin or ibuprofen.

The primary endpoint was incessant or recurrent pericarditis during 18-month follow-up; and this occurred significantly less frequently in the colchicine group than in the placebo group (17 percent vs. 38 percent; relative risk, 0.56; 95 percent confidence interval, 0.30-0.72). The investigators also reported fewer patients in the colchicine group developing persistent symptoms at 72 hours (19 percent vs. 40 percent; P=0.001). The remission rate at 1 week was higher in the colchicine group than in the placebo group (85 percent vs. 58 percent; P<0.001). The adverse-event rates were similar in the two groups.

Commenting on the study for Journal Watch, Harlan M. Krumholz, MD said that the findings strengthen the evidence for the use of colchicine to treat acute pericarditis. “Although these results may not surprise many clinicians, having the evidence to support this practice is reassuring,” he wrote. Dr. Reuben Ricallo with reports from NEJM and Journal Watch

By healthandlifestylemagazine Posted in CME Digest

CME DIGEST – September 2013


Electronic cigarettes rise to the occasion

E-cigs may be as effective as nicotine patches for smoking cessation

REGULATORY AUTHORITIES HAVE cautioned the public on the use of electronic cigarettes or e-cigs because there were no sufficient data previously to recommend its use by the public.

A recently published study in the Lancet have shown that e-cigs that deliver vaporized nicotine could be as effective for smoking cessation as nicotine patches. (Hibbert RM et al. Chest 2013 Aug)

CME DIGEST - Electronic cigarettes

In the study, around 650 adult smokers who expressed desire to quit were randomized to one of three treatments, to be taken as needed for 12 weeks: 16 mg nicotine e-cigarettes, 21 mg nicotine patches, or placebo e-cigarettes that did not contain nicotine. The study subjects also had access to telephone counseling service.

After six months, the three groups had similar quit rates (4 percent to 7 percent). But there were significantly more people in the nicotine e-cig group than the patch group who were able to reduce by half their cigarette consumption at six months (57 percent vs. 41 percent).

Although some limitations were noted in the study, a commentary on the study said that “health professionals will now hopefully feel easier about recommending e-cigarettes to smokers, or at least condoning their use.” With reports from Lancet and Physicians Journal Watch

By healthandlifestylemagazine Posted in CME Digest

CME DIGEST – September 2013


‘Gliptins’ and cardiovascular outcomes

Two short-term, industry-sponsored, randomized, international trials show neither increase or decrease in CV events with saxagliptin and alogliptin

SOME ORAL HYPOGLYCEMIC agents have been associated with increased cardiovascular (CV) events in previous trials. The relatively new antidiabetic agents, dipeptidyl peptidase–4 (DPP-4) inhibitors, have been shown in earlier meta-analysis to have a potential for cardioprotection, or at least, be neutral in terms of CV outcomes.

Two industry-sponsored randomized international trials examined that effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the primary endpoint of cardiovascular-related death, myocardial infarction, or stroke in patients with type 2 diabetes. (Scirica BM et al. for the SAVORTIMI 53 Steering Committee and Investigators, N Engl J Med 2013 Sep 2;White WB et al. for the EXAMINE Investigators. N Engl J Med 2013 Sep 2)

These clinical trials were conducted in response to the FDA’s requirement that cardiovascular safety be demonstrated for new antidiabetes drugs.

In the saxagliptin trial, 16,500 patients (mean age, 65; median duration of diabetes, 10 years) with additional cardiovascular risk factors or known cardiovascular disease received saxagliptin or placebo. During an average follow-up of 2 years, the primary endpoint was not significantly different in the two groups (7.3 percent and 7.2 percent); and there were no diff erences in secondary cardiovascular endpoints, except for slightly higher incidence of heart failure hospitalizations with saxagliptin (3.5 percent vs. 2.8 percent; P=0.007).

CME DIGEST - ‘Gliptins’

Looking at the glycosylated hemoglobin (HbA1c), it was 0.2 percent lower in the saxagliptin group than in the placebo group, and hypoglycemia was more common with saxagliptin (15.3 percent vs. 13.4 percent; P<0.001).

In the alogliptin trial, 5,400 diabetic patients who had suffered acute coronary syndrome during the previous 3 months were randomized to either alogliptin or placebo. Median followup was 1.5 years, showing the occurrence of the primary endpoint at 11.3 percent with alogliptin and 11.8 percent with placebo, indicating noninferiority (but not superiority) of alogliptin. Alogliptin lowered HbA1c by 0.3 percent compared with placebo, with no increase risk for hypoglycemia.

Dr. Allan S. Brett reviewed the two studies for Journal Watch and said that some people will look at these studies as showing that the “gliptin” drugs evaluated seem relatively safe, with no major adverse cardiovascular effects. He noted though the unexpected slight excess of heart failure cases with saxagliptin. On the other hand, others will contend that the drugs failed to improve cardiovascular outcomes. “Either way, the appropriate role for these drugs remains unclear, given their very high cost (about US$4,000 annually) and uncertainty about their long-term effects on clinically meaningful outcomes,” he wrote in his review. Dr. Reuben Ricallo with reports from NEJM and JW

By healthandlifestylemagazine Posted in CME Digest

CME DIGEST – September 2013


Endovascular vs. open repair of ruptured abdominal aortic aneurysms

A multicenter randomized controlled trial shows simlar outcomes with the two procedures

A RUPTURED ABDOMINAL aortic aneurysm (RAAA) is a surgical emergency requiring prompt detection and surgical management. Although there have been advances in operative technique and peri-operative management of these patients, it still carries a high mortality rate and incidence of complications.

It has been suggested in previous reports that a minimally invasive surgical technique such as endovascular repair (EVAR) may yield better results in terms of outcome in RAAA than open repair (OR). EVAR was introduced initially as a less invasive alternative to open surgery for elective repair of abdominal aortic aneurysms, but not RAAA.

CME DIGEST - Endovascular

Reimerink JJ et al., from the Department of Vascular Surgery, Academic Medical Center, Amsterdam, The Netherlands, conducted a multicenter randomized controlled trial evaluating EVAR versus OR in patients with RAAA. (Ann Surg 2013 Aug; 258:248)

In this study, 395 patients with RAAAs, who were admitted in the three hospitals involved in the trial, were enrolled. Anatomy was suitable for EVAR in 155 patients, 116 of whom ultimately were randomized to EVAR or open repair. The investigators found that the incidence of the primary composite endpoint — death or severe complications at 30 days — was not statistically signifi cantly diff erent in the two groups (42 percent vs. 47 percent; P=0.58).

Even when analyzed separately, each of the primary endpoint components occurred with similar frequency in the EVAR and open-repair groups. Rates of death and serious complications remained similar in the treatment groups at six months.

The authors concluded: “This trial did not show a significant difference in combined death and severe complications between EVAR and OR. Mortality for OR both in randomized patients and in cohort patients was lower than anticipated, which may be explained by optimization of logistics, preoperative CT (computerized tomography) imaging, and centralization of care in centers of expertise.

Reviewing the study for Journal Watch, Allan S. Brett, MD, noted that this study was conducted in an area where experienced centers were organized to off er around-the-clock emergency intervention for ruptured AAAs, and this might have impacted the results of the study, particularly the lower mortality and complication rate for open repair. Dr. Reuben Ricallo with reports from Ann Surg and JW

By healthandlifestylemagazine Posted in CME Digest

CM DIGEST – August 2013


Low-dose CT Screening for Lung Cancer

Benefit increases with risk levels

EARLY DETECTION is imperative in lung cancer, which always carries a grave prognosis when diagnosed late. A recently published study in the New England Journal of Medicine has shown that using low-dose CT (computerized tomography) screening for lung cancer could prevent the greatest number of deaths among those at highest risk. It also gives the lowest proportion of false-positives.

CME Digest - Low-dose CT Screening

In previous studies, CT screening was shown to reduce deaths by 20 percent compared with radiography. In the study, researchers stratified over 25,000 CT-screened patients into risk quintiles to examine whether the benefits of screening varied according to risk levels. The quintiles ranged from 0.15 percent to more than 2 percent in 5-year risk for lung cancer mortality.

The researchers reported that the percentage death reduction was constant across all quintiles, but that the number of deaths prevented was highest among those in the top three risk quintiles (77) versus those in the bottom two (11). Based on this study, the number needed to screen to prevent one lung cancer death was 208 for those in the top three quintiles, compared with 302 for the entire group. The researchers also noted that the false-positive results also declined significantly with increasing risk quintile. With reports from NEJM and Journal Watch

By healthandlifestylemagazine Posted in CME Digest

CME DIGEST – August 2013


Biomarker Screening for Heart Failure

BNP determination could be beneficial prevention strategy to proactively manage patients at risk for left ventricular dysfunction

AN INTERVENTION based on biomarker screening could guide clinicians on how to best proactively manage their patients with asymptomatic left ventricular dysfunction to prevent progression to worse stages of heart failure (HF).

The prevalence of HF continues to increase despite progress in understanding and treating risk factors. Ledwidge M et al conducted a nonblinded trial, enrolling 1,374 adults (average age, 65; 45 percent men) with =1 risk factor for HF (=3, 27 percent) (JAMA 2013 Jul 3).

All enrolled subjects underwent annual B-type natriuretic peptide (BNP) screening and were randomized to either BNP-guided intervention or usual care. The BNP results were not made available to providers.

CME Digest - Biomarker

Those with elevated BNP levels (=50 pg/mL) had an echocardiography done, and referred for collaborative specialist–primary care. The primary endpoint was the composite of new-onset HF and left ventricular (LV) systolic dysfunction, with or without symptoms. The study encountered a problem of slower-than-anticipated enrollment; hence, LV diastolic dysfunction was added to the composite endpoint later on.

The study had a mean follow-up of 4.2 years, and during this period, the revised primary endpoint occurred significantly less frequently in the intervention group than in the usual-care group (5.3 percent vs. 8.7 percent; odds ratio, 0.55). The rate of asymptomatic LV dysfunction was also lower in the intervention group (4.3 percent vs. 6.6 percent; OR, 0.57; P=0.01).

The risk for symptomatic HF did not diff er signifi cantly between the two groups (1.0 percent vs. 2.1 percent; OR, 0.48; P=0.12), but the investigators reported a signifi cantly reduced risk for emergency cardiovascular hospitalization in the intervention group (22.3 vs. 40.4 per 1000 patient-years). The investigators also noted that renin-angiotensin-aldosterone–inhibitors were used more in the intervention group than in the usual-care group (56.5 percent vs. 49.6 percent).

Commenting on the study in Journal Watch Cardiology, Frederick A. Masoudi, MD, MSPH, FACC, FAHA wrote that this study is important as “a relatively rigorous attempt to assess a preventive strategy for heart failure, but the results should not change practice.” He noted that the lack of blinding could explain some of the outcome diff erences; the importance of asymptomatic left ventricular dysfunction — especially echocardiographic diastolic abnormalities — is of questionable importance to patients; and the feasibility of implementing the intervention in large populations remains unclear. “Nonetheless, these fi ndings should initiate a robust discussion about HF prevention, including the value of biomarkers for this purpose,” he added. With reports from JAMA and JWC

By healthandlifestylemagazine Posted in CME Digest

CME DIGEST – August 2013


Uric Acid—Causal or Confounder in CHD?

Strong evidence of an effect of BMI on uric acid levels

HYPERURICEMIA has been established in previous studies as being strongly linked with higher risks for cardiovascular disease (CVD), specifically coronary heart disease (CHD) and hypertension. A recent study published in the British Medical Journal suggests that it is likely not a causal factor, but a confounder associated with higher body mass index (BMJ 2013;347:f4262).

CME Digest - Uric Acid

In this study, the researchers measured uric acid levels and did genetic analyses in two large Danish cohorts. Subjects were assessed for hypertension at study entry and were followed for the development of ischemic heart disease. They related covariables in 58,072 participants from the Copenhagen General Population Study and 10,602 from the Copenhagen City Heart Study, comprising 4,890 and 2,282 cases of ischemic heart disease, respectively. The main outcome used was blood pressure elevation and prospectively assessed ischemic heart disease.

Increases in uric acid were associated with increased risk for both CHD and hypertension, but the associations disappeared when taking into account the role of a common mutation in the SLC2A9 gene linked to high levels of uric acid. The presence or absence of the mutation showed no link with CHD risk, and higher BMI levels were independently associated with increased uric acid.

According to the authors, this study’s significance consists of the additional information to previous data on this subject, as follows:

  • Genetic variation at the SLC2A9 gene shows little evidence of a causal association between increased levels of uric acid, raised blood pressure, and risk of ischemic heart disease
  • However, causal analysis of body mass index shows strong evidence of an eff ect of body mass index on uric acid levels, suggesting considerable confounding in observational associations
  • Mendelian randomisation analysis suggests that uric acid is of limited clinical interest in ischaemic heart disease or blood pressure. But interventions to reduce body mass index could help improve the management of gout and related conditions such as urolithiasis. With reports from BMJ and Journal Watch
By healthandlifestylemagazine Posted in CME Digest

CMI DIGEST – August 2013


Androgen Deprivation in Prostate Cancer Treatment

In men with nonmetastatic prostate CA, ADT may cause excess risk for acute kidney injury

ANDROGEN DEPRIVATION therapy (ADT) is frequently prescribed for nonmetastatic prostate cancer. However, it lacks level-1 evidence to support its routine use and it is associated with higher risks for adverse effects, including metabolic syndrome, osteoporosis, and depressed libido.

CME Digest - Androgen

ADT may also have a negatively affect renal function due to treatment-induced testosterone suppression. Hence, Lapi F et al sought to determine the potential impact of ADT on the risk for acute kidney injury (AKI) (JAMA 2013 Jul 17).

The study was a retrospective, nested, case-control analysis involving 10,250 men (age, =40) with nonmetastatic prostate cancer and no history of metastatic disease or serious renal or liver disease. Patients came from the robust United Kingdom Clinical Practice Research Datalink in combination with the Hospital Episodes Statistics database. A total of 232 cases with first-ever AKI admission (incidence rate,5.5 per 1000 person-years) were identifi ed and matched with 2,721 controls without AKI. ADTs consisted of any of the following: gonadotropinreleasing hormone agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, or combinations of these treatments. ADT exposure was categorized as current use, past use, or never use.

The researchers noted that current use of any ADT significantly increased risk for AKI versus never use, generating a rate difference of 4.43 per 1000 persons per year. Past use did not significantly increase risk for AKI versus never use.

Reviewing the study for Journal Watch, Robert Dreicer, MD, MS, FACP described it as “provocative,” but the findings remain as hypothesis-generating. He said that since no prior study has addressed this issue, they must be replicated in other settings. “Our current understanding of the risks associated with androgen deprivation therapy should preclude its routine use in patients with prostate-specific antigen (PSA)-only disease, especially in those with prolonged PSA doubling times,” he wrote. With reports from JAMA and Journal Watch

By healthandlifestylemagazine Posted in CME Digest

CME DIGEST – June 2013


How to survive a flu pandemic — lessons from 1918–1919

Implementing public health interventions lowered mortality rates in U.S. cities during the 1918–1919 influenza pandemic

Although we have made advances in the development of vaccines and antiviral agents, an influenza pandemic would probably overwhelm our capacity to produce and distribute these materials. Attention is now being paid to other interventions to control a pandemic — for example, school closure and isolation and quarantine. How effective would such measures be? To address this question, investigators systemically reviewed historical data on the 1918–1919 influenza pandemic.

Using census reports and public health records, the researchers gathered information on weekly pneumonia and influenza mortality rates and nonpharmaceutical interventions undertaken in 43 large U.S. cities from September 8, 1918, through February 22, 1919. During this 24-week period, 115,340 excess influenza and pneumonia deaths occurred in these cities.

All of the cities adopted at least one of three major public health interventions: school closure, a public-gathering ban, or isolation and quarantine. The most frequently implemented combination of interventions was school closure together with a public-gathering ban. Early implementation of interventions was significantly associated with delayed time to reaching peak mortality rates, reduced peak mortality rates, and a reduced total mortality burden; increased duration of the interventions was significantly associated with a reduced total mortality burden. These beneficial effects were independent of population size, population density, and sex and age distributions.

Comment: There are obvious limitations in trying to assess the effectiveness of public health interventions using 90-year-old data. Furthermore, vast social and cultural changes have occurred in the U.S. since 1918; whether the effect of these public health measures would be comparable today is unclear. Still, these findings provide evidence to support instituting such measures, should we experience another flu pandemic comparable to the one in 1918–1919. Richard T. Ellison III, MD, published in Journal Watch Infectious Diseases

By healthandlifestylemagazine Posted in CME Digest