Friday, October 23, 2015

Measurement of ventricular repolarization dispersion in chest pain

Although the authors of this paper, for purposes of discussion, use the generally accepted term “NSTEMI” in reference to acute coronary syndrome with subtle or non diagnostic ECG patterns, their findings suggest that the term is simplistic and of limited clinical usefulness.  Utilizing a specialized electrocardiographic technique to measure ventricular repolarization dispersion in  patients presenting with chest  pain they found:

Methods and Results We continuously recorded 12‐lead Holter ECGs from chest pain patients upon their arrival to the ED. VRD was quantified using principal component analysis of the 12‐lead ECG to compute a T‐wave complexity ratio (ie, ratio of second to first eigenvectors of repolarization). Clinical outcomes were obtained from hospital records. The sample was composed mainly of older males (n=369; ages 63±12 years; 63% males), and 92 (25%) had NSTEMI and 26 (7%) had MACEs. Baseline T‐wave complexity ratio modestly correlated with peak troponin levels (r=0.41; P less than 0.001) and was a good classifier of NSTEMI events (area under the curve=0.70). An increased T‐wave complexity ratio on the presenting ECG was strongly associated with NSTEMI (odds ratio [OR]=3.8 [2.1 to 5.8]) and in‐hospital MACE (OR=8.2 [3.1 to 21.5]).

Conclusions A simple measure of global VRD on the presenting 12‐lead ECG correlates with ischemic myocardial injury and can discriminate NSTEMI cases very early during evaluation. Prospective studies should validate these findings and test whether VRD can guide therapy.

More from the discussion section of the paper:

As such, our data suggest that a simple measure of T‐wave complexity is more sensitive for (1) detecting ischemic myocardial necrosis associated with NSTEMI and (2) quantifying the severity of ischemic burden to identify high‐risk NSTEMI patients who would benefit from early revascularization.

This paper convinces me more than ever that the STEMI/NSTEMI terminology needs to be abandoned.  If there is a meaningful binary distinction in ACS it would be between coronary occlusion and plaque instability without occlusion.   But the current STEMI/NSTEM designation is, according to increasing evidence and for multiple reasons, a poor surrogate tor presence of absence of occlusion.  Moreover, according to the data presented here, the decision for early cardiac catheterization ought to be based on assessment along a continuum of risk rather than a binary distinction.

Thursday, October 22, 2015

Uric acid level as a marker for renal hemodynamics

Free full text review here concludes:

The results of many clinical and experimental studies clearly demonstrate that an increasing serum uric acid level may be a useful biomarker of hypertension and its consequently deranged renal hemodynamics. It is also evident that chronic hyperuricemia may adversely affect cardiovascular and renal structure and function and, therefore, may be a contributory event in the pathogenesis of cardiovascular and renal disorders. Thus, at present, there is no clear or convincing evidence that hyperuricemia is a causative factor in hypertensive disease or that lowering the uric acid concentration may reduce arterial pressure. Therefore, conventional pharmacotherapy, without uricosuric agents, is recommended in the treatment of hypertensive cardiovascular disease unless there is concern about tissue deposition of urate. One exception may be the population of obese hypertensive adolescents in whom reduction of hyperuricemia has been shown to result in a decreased arterial pressure.

Wednesday, October 21, 2015

Under diuresis of patients hospitalized with heart failure

---was associated with higher mortality and readmission rates in this study. A simple score based on orthopnea and pedal edema proved useful.

Tuesday, October 20, 2015

What is the best way to evaluate thrombocytopenia in the ICU?

Should we use a systematic approach to evaluate it as fully as possible? Traditionally we're more selective. We formulate an overall clinical impression, then specifically assess for things that are really horrible and require specific action (TTP, HIT).

A small before and after study compared the traditional selective approach with one in which all patients were evaluated as fully as possible:


Before-and-after study of all patients with thrombocytopenia was used. ‘Before’ group had no intervention. New standard operating procedures for thrombocytopenia management were introduced. In the ‘After’ group, bone marrow aspiration; determination of fibrinogen dosage, prothrombin time, factor V, D-dimers; assay of fibrin monomers, ferritin, triglycerides, lactic acid dehydrogenase, aspartate transaminase, alanine aminotransferase, vitamin B12, folates, reticulocytes, haptoglobin, and bilirubin were performed.


In the Before group (n = 20), the mechanism (central, peripheral, or mixed) was identified in 10 % versus 83% in After group (n = 23) (p less than 0.001) (48% peripheral, 35% mixed). Before intervention, greater than or equal to 1 etiology was identified in 15% versus 95.7% in the After group (p less than  0.001).


Systematic and extensive investigation using routine tests highlights the mechanisms and etiology of thrombocytopenia in most cases.

More patients in the traditional group had normalization of platelet counts than did those who were fully evaluated. Evaluation in the traditional group did not drive any treatment. In the fully evaluated group two patients were given folic acid based on the evaluation and one received corticosteroids and IVIG after a bone marrow finding of hemophagocytosis.

Saturday, October 17, 2015

Friday, October 16, 2015

Interatrial block

Reported here are two cases in which the block was intermittent (second degree) and seen during hemodialysis.

Wednesday, October 14, 2015

Paraneoplastic neurologic disorders in small cell lung cancer are more common than appreciated

---in this study:

Methods: Two hundred sixty-four consecutive patients with biopsy-proven SCLC were recruited at the time of tumor diagnosis. All patients underwent full neurologic examination. Serum samples were taken prior to chemotherapy and analyzed for 15 neuronal antibodies…

Results: PNDs were quite prevalent (n = 24, 9.4%), most frequently Lambert-Eaton myasthenic syndrome (3.8%), sensory neuronopathy (1.9%), and limbic encephalitis (1.5%). Eighty-seven percent of all patients with PNDs had antibodies to SOX2 (62.5%), HuD (41.7%), or P/Q VGCC (50%), irrespective of their syndrome. Other neuronal antibodies were found at lower frequencies (GABAb receptor [12.5%] and N-type VGCC [20.8%]) or very rarely (GAD65, amphiphysin, Ri, CRMP5, Ma2, Yo, VGKC complex, CASPR2, LGI1, and NMDA receptor [all less than 5%]).

Conclusions: The spectrum of PNDs is broader and the frequency is higher than previously appreciated, and selected antibody tests (SOX2, HuD, VGCC) can help determine the presence of an SCLC.

Some background from the full text of the paper:

Currently almost half of all patients diagnosed with PNDs have associated SCLC,2 so this study is relevant to the broad epidemiology of these neurologic disorders. We found a higher frequency of PNDs (9.1% of SCLC) than previous SCLC surveys, perhaps because of the single-center prospective design with neurology input and high recruitment among the SCLC population. The findings suggest that PNDs in patients with SCLC may be underdiagnosed due to misattribution of symptoms; recognition of the disorders and their common antibody associations is important because the earlier the diagnosis is made, the better the oncologic and neurologic outcome.23,24

Tuesday, October 13, 2015

Causes of sudden cardiac death in athletes

From a large NCAA database as reported in Circulation:

Conclusions—The rate of SCD in National Collegiate Athletic Association athletes is high, with males, black athletes, and basketball players at substantially higher risk. The most common finding at autopsy is autopsy-negative sudden unexplained death. Media reports are more likely to capture high-profile deaths, and insurance claims are not a reliable method for case identification.

Monday, October 12, 2015

Point of care lung ultrasound

Here's a nice free full text review in the Annals of Intensive Care.

Saturday, October 10, 2015

The link between obesity and pancreatic cancer

In a recent analysis of surgical specimens obesity (with visceral fat more strongly associated than subcutaneous fat) was associated with pancreatic intraepithelial neoplasia (PanIN), a known precancerous condition.

A related editorial discusses other evidence, from epidemiology and animal studies, in support of the association and comments on possible mechanisms mediated by inflammation.

Friday, October 09, 2015

Another study on oxygen administration in acute MI

From the study:

Methods and Results—We conducted a multicenter, prospective, randomized, controlled trial comparing oxygen (8 L/min) with no supplemental oxygen in patients with ST-elevation–myocardial infarction diagnosed on paramedic 12-lead ECG. Of 638 patients randomized, 441 patients had confirmed ST-elevation–myocardial infarction and underwent primary end-point analysis. The primary end point was myocardial infarct size as assessed by cardiac enzymes, troponin I, and creatine kinase. Secondary end points included recurrent myocardial infarction, cardiac arrhythmia, and myocardial infarct size assessed by cardiac magnetic resonance imaging at 6 months. Mean peak troponin was similar in the oxygen and no oxygen groups (57.4 versus 48.0 μg/L; ratio, 1.20; 95% confidence interval, 0.92–1.56; P=0.18). There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group (1948 versus 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04–1.52; P=0.01). There was an increase in the rate of recurrent myocardial infarction in the oxygen group compared with the no oxygen group (5.5% versus 0.9%; P=0.006) and an increase in frequency of cardiac arrhythmia (40.4% versus 31.4%; P=0.05). At 6 months, the oxygen group had an increase in myocardial infarct size on cardiac magnetic resonance (n=139; 20.3 versus 13.1 g; P=0.04).

Conclusion—Supplemental oxygen therapy in patients with ST-elevation–myocardial infarction but without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at 6 months.

Thus we have even more evidence that oxygen administration in the absence of hypoxemia is harmful. This study, however, may have limited applicability to real world situations because the patients receiving oxygen got 8 L/minute, much more than traditionally used.

Thursday, October 08, 2015

How central obesity drives insulin resistance

This paper explains the mechanisms in detail, which include secretion of inflammatory mediators by visceral fat (adipokines) which in turn interfere with the post insulin receptor cascade at multiple sites.

Wednesday, October 07, 2015

Failed NIPPV associated with more intubation complications

From a recent study:


This is a single-center retrospective cohort study of 235 patients intubated between 1 January 2012 and 30 June 2013 in a medical ICU of a university medical center. A total of 125 patients were intubated after failing NIPPV, 110 patients were intubated without a trial of NIPPV. Intubation-related data were collected prospectively through a continuous quality improvement (CQI) program and retrospectively extracted from the medical record on all patients intubated on the medical ICU. A propensity adjustment for the factors expected to affect the decision to initially use NIPPV was used, and the adjusted multivariate regression analysis was performed to evaluate the odds of a composite complication (desaturation, hypotension, or aspiration) with intubation following failed NIPPV versus primary intubation.


A propensity-adjusted multivariate regression analysis revealed that the odds of a composite complication of intubation in patients who fail NIPPV was 2.20 (CI 1.14 to 4.25), when corrected for the presence of pneumonia or acute respiratory distress syndrome (ARDS), and adjusted for factors known to increase complications of intubation (total attempts and operator experience). When a composite complication occurred, the unadjusted odds of death in the ICU were 1.79 (95% CI 1.03 to 3.12).


After controlling for potential confounders, this propensity-adjusted analysis demonstrates an increased odds of a composite complication with intubation following failed NIPPV. Further, the presence of a composite complication during intubation is associated with an increased odds of death in the ICU.

The authors go on to cite previous data showing that failed NIPPV is associated with increased mortality. Prior studies suggest that it is mainly patients with acute on chronic respiratory failure (notably COPD) who experience a net mortality benefit with the use of NIPPV. Other forms of respiratory failure (i.e. hypoxemic respiratory failure) are associated with a high rate of NIPPV failure.

The authors cite this paper, a 2012 systematic review, which concludes:

In summary, for patients with acute respiratory failure due to severe exacerbations of COPD or congestive heart failure, NPPV plus supportive care shows important reductions in mortality and intubation rates compared with supportive care alone. BPAP has been studied more rigorously, but direct comparisons of CPAP and BPAP in patients with ACPE show similar efficacy. Current evidence suggests potential benefit for patients with acute respiratory failure who are postoperative or post-transplant and as a method to facilitate weaning from invasive ventilation or prevent recurrent postextubation respiratory failure in those at high risk. However, the evidence for these indications is much weaker. Limited evidence shows similar treatment effects across different settings and the possibility of less benefit in trials designed to replicate usual clinical practice. There is a clear need for further studies in patient populations where NPPV has not been rigorously studied and to understand the role of training and effectiveness when used as part of routine clinical care.

The implication form all these studies is that NIPPV should not be used for respiratory failure other than that caused by COPD or cardiogenic pulmonary edema, though no strong recommendation is made to that effect.

Monday, October 05, 2015

Topic review on mesenteric venous thrombosis

Free full text is available for this article.

One of the pitfalls in diagnosis is confounding by conditions that are known risk factors for MVT:

Unfortunately, significant delays often occur between presentation and the diagnosis of MVT because of the nonspecific nature of symptoms. For example, pain resulting from MVT after abdominal surgery is often mistakenly assumed to be postoperative discomfort. Pain in the setting of inflammatory bowel disease is often attributed to disease exacerbation. A high index of suspicion and rapid diagnosis are critical to prevent delays in therapy and adverse outcomes.

Sunday, October 04, 2015

Mood disorders predispose youth to precocious cardiovascular disease

---according to an AHA statement.

Concerning possible mechanisms, according to the paper:

In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications.

Friday, October 02, 2015

Langerhans cell histiocytosis

Here's a great review from Blood's How I Treat series.

Thursday, October 01, 2015

Changing epidemiology of rheumatic fever and updated Jones criteria

The American Heart Association has published a new scientific statement on this topic. The changing epidemiology is fascinating and somewhat poorly understood. From the paper:

It is well established that during the 20th century, the incidence of ARF and the prevalence of RHD declined substantially in Europe, North America, and developed nations in other geographic locations…

Although sporadic cases of ARF continue to be seen in affluent nations, the major burden is currently found in low- and middle-income countries and in selected indigenous populations elsewhere. The pattern of disease in the high-prevalence regions is often hyperendemic, with cases occurring throughout the year and a virtual absence of outbreaks. This is in contrast to high-income settings, which experience a low background incidence of ARF with periodic outbreaks.28,43

There is also evidence of differences in incidence even in populations within the same country, which further demonstrates the disproportional disease burden. For example, although the overall mean incidence of ARF in New Zealand rose by 55% over the past 2 decades, the incidence of ARF among the non-Maori/Pacific New Zealand populations declined by 70% over the same period.44 Similar discrepancies in disease burden exist in Australia, where the indigenous population experiences one of the world’s highest reported incidences of ARF at 153 to 380 cases per 100 000 people per year in the 5- to 14-year-old age group,45 whereas in other Australian populations, the incidence approximates European and North American levels.

In summary, the global distribution of ARF/RHD is clearly disproportionate. Certain geographic regions and specific ethnic and socioeconomic groups experience very high rates of ARF incidence, whereas in other regions, the disease has virtually disappeared…

Because the clinical utility of a diagnostic test is determined by a number of factors, including its pretest probability and background disease prevalence, and in view of the heterogeneity in global disease burden noted above, a single set of diagnostic criteria may no longer be sufficient for all population groups and in all geographic regions. To avoid overdiagnosis in low-incidence populations and to avoid underdiagnosis in high-risk populations, variability in applying diagnostic criteria in low-risk compared with high-risk populations is reasonable, as has been promulgated by the Australian rheumatic fever guidelines.

The new criteria would increase the sensitivity. The major change concerns assessment for carditis, in which echocardiography will assume a larger role, in recognition of the improved echocardiographic technology and declining auscultatory skills.