Heart failure with preserved ejection fraction. / Hjertesvikt med normal ejeksjonsfraksjon.

BACKGROUND: Approximately one half of all patients with heart failure have normal ejection fraction in the left ventricle, and heart failure is attributed to stiffness of the cardiac muscle. The most common cause is hypertension with ventricular hypertrophy. MATERIAL AND METHOD: Literature searches were conducted in PubMed. After we made our selection, a total of 15 articles on heart failure with normal ejection fraction were included. In addition, we included nine articles from our own literature archive. RESULTS: The diagnosis of heart failure with normal ejection fraction presupposes clinical findings consistent with heart failure and objective signs of diastolic dysfunction. The main objective sign is increased left ventricular filling pressure estimated by echocardiography. Ventricular hypertrophy and increased natriuretic peptides support the diagnosis. INTERPRETATION: Underlying conditions and symptoms are treated, and in general the same drugs are used as for heart failure with reduced ejection fraction.

A 13-Year Retrospective Study of Basal Cell Carcinoma in a Canadian Dermatology Practice: A Comparison Between Anatomical Location and Histopathologic Subtypes.

BACKGROUND: It is unknown whether the histologic subtypes of basal cell carcinoma (BCC) arise from a common progenitor cell or whether other factors play a role in their development. OBJECTIVE: To investigate the relationship between the different BCC histopathologic subtypes and anatomical distribution of BCCs in a Canadian dermatology practice. METHODS: The charts of all patients diagnosed with BCC between 1993 and 2005 from a single private dermatology practice in Vancouver, Canada, were reviewed. Descriptive data analysis was undertaken to look at the distribution of histologic subtypes based on age, gender, and anatomical location. RESULTS: Nodular BCCs accounted for 58% of all tumors. Sixty-six percent of these were situated on the head/neck (odds ratio [OR] = 3.0, 95% confidence interval [CI] = 2.1-4.3, P < .0001). Infiltrative (OR = 2.4, 95% CI = 1.5-4.1, P = .0003) and superficial BCCs were more common in women (OR = 3.7, 95% CI = 2.5-5.7, P < .0001), affected the trunk (OR = 3.2, 95% CI = 2.1-4.9, P < .0001), and appeared in younger individuals (OR = 1.8, 95% CI = 1.2-2.7, P = .004). CONCLUSION: Our results show a preference of distinct BCC subtypes for certain anatomical locations.

A review of the diagnosis and management of erythroderma (generalized red skin).

Erythroderma is a condition caused by several etiologies that result in red inflamed skin on 90% or more of the body surface. To optimize the diagnosis and management of the erythrodermic patient, healthcare professionals should be familiar with the underlying etiologies and treatment modalities. Patients with erythroderma require immediate attention as they may face a variety of medical complications. Early detection and effective management of these complications significantly reduce mortality and morbidity of this potential dermatologic emergency. This review highlights the underlying common diagnoses, assessment, and management of the patient with erythroderma.

Cancers mimicking fungal infections.

Primary and metastatic malignancies may occasionally mimic or coexist with cutaneous fungal infections. The authors report 3 cases of cancers that were initially presumed to be cutaneous fungal infections. Dermatologists should maintain a low threshold for skin biopsy in patients with persistent or refractory fungal infections.

Application of sSPhos as a Chiral Ligand for Palladium-Catalyzed Asymmetric Allylic Alkylation.

Palladium-catalyzed asymmetric allylic alkylation is a versatile method for C-C bond formation. Many established classes of chiral ligands can perform allylic alkylation reactions enantioselectively, but identification of new ligand classes remains important for future development of the field. We demonstrate that enantiopure sSPhos, a bifunctional chiral monophosphine ligand, when used as its tetrabutyl ammonium salt, is a highly effective ligand for a benchmark Pd-catalyzed allylic alkylation reaction. We explore the scope and limitations and perform experiments to probe the origin of selectivity. In contrast with reactions previously explored using enantiopure sSPhos, it appears that steric bulk around the sulfonate group is responsible for the high enantioselectivity in this case, rather than attractive noncovalent interactions.

A review of the clinical variants and the management of psoriasis.

PURPOSE: To enhance the learner's competence with knowledge of the clinical variants and management of psoriasis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Demonstrate knowledge of the types, symptoms, and diagnostic testing of psoriasis.2. Apply knowledge of psoriasis treatment to patient care scenarios. ABSTRACT: Psoriasis is an inflammatory skin condition that is associated with various comorbidities. To the wound care physician, the Koebner phenomenon is of importance, as any superficial trauma can induce psoriasis. Particularly, periwound and joints are particularly susceptible to flare-ups of this condition. This review highlights the epidemiology and treatment of psoriasis.

Sickle cell disease and leg ulcers.

Sickle cell disease is a genetic disorder of hemoglobin synthesis leading to a deformation of the red blood cell. This disorder is associated with painful, slow-to-heal leg ulcers. This article discusses the wound bed preparation paradigm as a guide to the treatment of sickle cell-associated leg ulcers.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels 3 months after myocardial infarction are more strongly associated with magnetic resonance-determined ejection fraction than NTproBNP levels in the acute phase.

BACKGROUND: The relationship between levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular function determined by magnetic resonance imaging (MRI) in ST-segment-elevation myocardial infarction (STEMI) is largely unknown. METHODS AND RESULTS: This was a substudy of the Norwegian Study on District Treatment of STEMI, in which patients received thrombolysis followed by early or late invasive strategy. NT-proBNP was measured at 3 days and 3 months after the myocardial infarction, and magnetic resonance imaging was performed after 3 months (n = 160). Log NT-proBNP levels at both time points were significantly associated with ejection fraction (EF) (r(2) values 0.25 and 0.42, respectively) as well as infarct size (r(2) values 0.38 and 0.47, respectively; P < .0001 for all, adjusted for confounders). Furthermore, receiver operating characteristic (ROC) curves used to analyze the ability of NT-proBNP to discriminate long-term low EF (≤40%) and large infarct size (≥15.7%), were significant at both time points (P < .001 for all). Pairwise comparison of the ROC curves showed a significantly better performance of NT-proBNP at 3 months compared with 3 days for discrimination of low EF (P = .023). CONCLUSION: Repeated measurements of NT-proBNP in STEMI patients showed that NT-proBNP levels at 3 months were more strongly associated with long-term EF and infarct size than NT-pro BNP levels after 3 days. Our data suggest that measurement of NT-proBNP 3 months after myocardial infarction is a better indicator of left ventricular function compared with NT-proBNP in the acute phase.

Assessment of left ventricular function in ST-elevation myocardial infarction by global longitudinal strain: a comparison with ejection fraction, infarct size, and wall motion score index measured by non-invasive imaging modalities.

AIMS: We aimed to compare two-dimensional global longitudinal strain (GS) with different non-invasive imaging modalities for the assessment of left ventricular function in an ST-elevation myocardial infarction population. METHODS AND RESULTS: GS was compared with ejection fraction (EF) determined by magnetic resonance imaging (MRI), standard echocardiography (echo), contrast echo, and electrocardiography-gated single-photon emission computed tomography (SPECT), as well as with MRI-determined relative infarct size and echo-determined wall motion score index (WMSI), in 163 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). The linear relation between GS and standard echo (r(2)= 0.43, P <0.001), contrast echo (r(2)= 0.38, P <0.001), and SPECT-determined EF (r(2)= 0.52, P <0.001) was almost identical as that between GS and the gold standard MRI-determined EF (r(2)= 0.47, P <0.001). GS was best associated with WMSI by echo (r(2)= 0.55, P <0.001), while the associations between GS and relative infarct size were weaker (r = 0.43, P <0.001). Receiver operator characteristics curves, used to analyse the ability of GS to discriminate low EF (≤ 40%) measured by the four different modalities, large myocardial infarction (MI ≥ 15.7%), and high WMSI (≥ 1.5), were significant for all. GS was shown to be the best predictor of low EF measured by MRI [area under the curve (AUC) 0.965], while the lowest AUC was found between GS and large MI (0.814). CONCLUSION: Global strain is associated well with EF measured by all modalities. Global strain was found to be the best predictor of low EF measured by the gold standard MRI. Since global strain is an inexpensive test, these data may be of health economic interest.

Left ventricular function in acute myocardial infarction treated with thrombolysis followed by early versus late invasive strategy.

BACKGROUND: Thrombolysis remains the treatment of choice in acute ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed within 90 to 120 minutes. The optimal treatment after thrombolysis is still debated, but several studies have shown improved clinical outcomes with early transfer for PCI. The aim of this study was to investigate whether an early invasive strategy after thrombolysis preserved left ventricular function better than a late invasive strategy. METHODS: This was a substudy of the NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction. Patients with STEMI of <6 hours of duration and >90 minutes of expected transfer delays to PCI were treated with aspirin, tenecteplase, enoxaparin, and clopidogrel and randomized to early or late invasive strategy (N = 266). Left ventricular volumes and ejection fraction were assessed by single-photon emission computed tomography, echocardiography, and magnetic resonance imaging 3 months after the index infarction. RESULTS: Noninvasive imaging was completed in 241 patients (91%). Median end-diastolic and end-systolic volumes after 3 months did not differ between groups. Median ejection fraction was well preserved and also without differences: 63% (interquartile range 51-70) in the early invasive versus 65% (interquartile range 55-71) in the late invasive group when assessed by single-photon emission computed tomography (P = .30), 55% versus 55% when assessed by echocardiography (P = .88), and 57% versus 57% when assessed by magnetic resonance imaging (P = .99). CONCLUSION: In this group of STEMI patients treated with thrombolysis, no difference in left ventricular function after 3 months was found between patients treated with early versus late invasive strategy.

Assessment of left ventricular function with magnetic resonance imaging vs. echocardiography, contrast echocardiography, and single-photon emission computed tomography in patients with recent ST-elevation myocardial infarction.

AIMS: Magnetic resonance imaging (MRI) is often considered to be the gold standard in measuring left ventricular function and volumes. The aim of this study was to assess the agreements between standard echocardiography (standard echo), contrast echocardiography (contrast echo), single-photon emission computed tomography (SPECT), and MRI in the determination of left ventricular ejection fraction (EF) and end-diastolic volumes (EDV) in patients treated for acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Standard echo, contrast echo, SPECT and MRI were performed on the same day, 3 months after STEMI in 150 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). Bland-Altman analysis of EF measured by all four imaging modalities showed generally low mean differences but wide limits of agreement. The mean EDV difference, however, was consistently higher when MRI was compared with standard echo (54.9 mL), contrast echo (41.7 mL) and SPECT (54.6 mL), and the limits of agreement were wider. The mean EDV differences between contrast echo vs. standard echo, SPECT vs. standard echo and contrast echo vs. SPECT were small. CONCLUSION: Our data suggest that all four imaging modalities measured EF closely similar after STEMI as demonstrated by a very small bias. The limits of agreement were however wide. EDV measured by MRI was consistently higher when compared with the other methods which may be caused by different tracing-methods and imaging principles. As echocardiography is preferable from a cost-benefit point of view, further analysis would be needed to clarify the nature of such differences.

Medical Therapies for Heart Failure With Preserved Ejection Fraction.

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

A review of adverse cutaneous drug reactions resulting from the use of interferon and ribavirin.

Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.

The effectiveness of the Ivan H. Smith Memorial Studentships program on encouraging medical students to pursue a career in radiation oncology.

BACKGROUND: Founded in 1963, the Ivan H. Smith Memorial Studentship (ISMS) is a summer program that familiarizes students with the work of several cancer centers and aims to attract medical students into oncology. METHODS: In this study, we attempted to evaluate the impact of the ISMS Program on career choice in radiation oncology (RO). RESULTS: There were 5.9 times as many ISMS recipients from 1971 to 1981 who completed training in RO compared to the number of graduates exiting post-MD training in RO in 1989. CONCLUSION: Although few former ISMS students entered RO, the ISMS encourages medical students into this field.

Catalytic asymmetric synthesis of geminal-dicarboxylates.

Stereogenic acetals, spiroacetals and ketals are well-studied stereochemical features that bear two heteroatoms at a common carbon atom. These stereocenters are normally found in cyclic structures while linear (or acyclic) analogues bearing two heteroatoms are rare. Chiral geminal-dicarboxylates are illustrative, there is no current way to access this class of compounds while controlling the stereochemistry at the carbon center bound to two oxygen atoms. Here we report a rhodium-catalysed asymmetric carboxylation of ester-containing allylic bromides to form stereogenic carbon centers bearing two different carboxylates with high yields and enantioselectivities. The products, which are surprisingly stable to a variety of acidic and basic conditions, can be manipulated with no loss of enantiomeric purity as demonstrated by ring closing metathesis reactions to form chiral lactones, which have been extensively used as building blocks in asymmetric synthesis.