Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world

Background

In 2005, 80% of cardiovascular disease (CVD) deaths occurred in low- to middle-income countries (i.e., developing nations). Cardiovascular imaging, such as myocardial perfusion SPECT, is one method that may be applied to detect and foster improved detection of at-risk patients. This document will review the availability and utilization for nuclear cardiology procedures worldwide and propose strategies to devise regional centers of excellence to achieve quality imaging around the world.

Methods

As a means to establish the current state of nuclear cardiology, International Atomic Energy Agency member and non-member states were queried as to annual utilization of nuclear cardiology procedures. Other sources for imaging statistics included data from medical societies (American Society of Nuclear Cardiology, European Society of Cardiology, and the European Association of Nuclear Medicine) and nuclear cardiology working groups within several nations. Utilization was calculated by dividing annual procedural volume by 2007 population statistics (/100,000) and categorized as high (>1,000/100,000), moderate-high (250-999/100,000), moderate (100-249/100,000), low-moderate (50-99/100,000) and low (<50/100,000).

Results

High nuclear cardiology utilization was reported in the United States, Canada, and Israel. Most Western European countries, Australia, and Japan reported moderate-high utilization. With the exception of Argentina, Brazil, Colombia and Uruguay, South America had low usage. This was also noted across Eastern Europe, Russia, and Asia. Utilization patterns generally mirrored each country’s gross domestic product. However, nuclear cardiology utilization was higher for developing countries neighboring moderate-high “user” countries (e.g., Algeria and Egypt); perhaps the result of accessible high-quality training programs.

Conclusions

Worldwide utilization patterns for nuclear cardiology vary substantially and may be influenced by physician access to training and education programs. Development of regional training centers of excellence can guide utilization of nuclear cardiology through the application of guideline- and appropriateness-driven testing, training, continuing education, and quality assurance programs aiding developing nations to confront the epidemics of CVD.     

Immunoglobulin heavy chain allotypes in a sample of Sicilian patients with celiac disease

The authors have studied the immunoglobulin heavy chain allotypes in 14 Sicilian patients with celiac disease (CD) and in 75 healthy controls. No association has been found between CD and Gm or Km phenotypes. When the role of Gm phenotypes in immune response against gliadin was analyzed, fb-positive CD patients on gluten-free diet for 1 year showed an increased antigliadin IgG response. Comparing the values of fb-positive subjects with those of negative ones, a significant difference was observed. These data, demonstrating that the presence or absence of a phenotype is able to define the breadth of immune response against alpha-gliadin antigen, are indicative of the role played by Ig allotypes in CD.     

Role of tachykininergic and cholinergic pathways in modulating canine gastric tone and compliance in vivo.

Acetylcholine and tachykinins act as co-transmitters along excitatory pathways at different gut levels. Since cholinergic pathways are involved in maintaining gastric tone during fasting, our aim was to study the possible role of tachykininergic pathways in modulating canine gastric tone and compliance in vivo by using selective tachykinin receptor antagonists. In four fasting, conscious dogs, we characterized the pressure-volume relationship in the proximal stomach by using a barostat. We increased the pressure of the intragastric bag by 2 mmHg increments every 3 min, starting from a baseline value of 2 up to 12 mmHg. Drug effects were investigated by studying pressure-volume relationships before and 15 min after intravenous (i.v.) administration of SR140333, SR48968, or SR142801 (respectively, NK (1)-, NK (2)-, and NK (3)-receptor antagonist, each at the dose of 1 mg kg (-1)) or atropine (100 microg kg (-1)). Pressure-volume curves were fitted by nonlinear regression analysis. Before drug administration, the curve that best fitted the pressure-volume relationship was exponential. SR140333, SR48968 and SR142801 did not affect baseline gastric tone or the gastric pressure-volume curve at any distension level. At a distending pressure of 6 mmHg, the Delta volumes obtained after administration of SR140333, SR48968 or SR142801 vs control were 65 +/- 28, 27 +/- 26, 14 +/- 20 ml, respectively. The same was true even when all three antagonists were administered together to achieve simultaneous blockade of all three tachykinin receptor subtypes. Atropine increased baseline gastric volume (Delta volume = 237 +/- 15 ml; P< 0.01) and significantly (P< 0.0001) shifted the pressure-volume curve to the left. After atropine, a linear equation best fitted the pressure-volume curve. We conclude that tachykininergic pathways are not involved in modulating canine gastric tone and compliance during fasting, whereas cholinergic pathways play a major role not only in maintaining gastric tone, but also in modulating the compliance of the proximal stomach to a distending stimulus.     

The clinical usefulness of electrocardiogram-gated Tc-99 m methoxy-isobutyl-isonitrile images in the detection of basal wall motion abnormalities and reversibility of stress induced perfusion defects

Technetium-99 m methoxy-isobutyl-isonitrile (SESTAMIBI) has been recently introduced to trace regional myocardial perfusion. Beyond blood flow distribution, a quantitative index of regional myocardial wall motion from SESTAMIBI electrocardiogram (ECG)-gated images was obtained, according to the assumption that changes in the detected radioactivity reflect changes in myocardial wall thickness during the cardiac cycle. As a preliminary study, 20 patients with coronary artery disease and regional wall motion abnormalities and 15 normal subjects were studied by SESTAMIBI scintigraphy and contrast ventriculography. Regional wall motion was analyzed by a radial method applied to both techniques. Absolute systolic changes in radioactivity and its ratio to reference normal values (wall thickening index, WTI) were determined in 9 anatomical cardiac regions according to the formula (endsystolic counting profile — enddiastolic counting profile/enddiastolic counting profile) × 100. The overall agreement between radioisotopic and ventriculographic techniques was 88% (158 of 180 segments). Normal, hypokinetic and akinetic ventriculographic segments showed WTI values of 1.1±0.2, 0.8±0.2 and 0.4 ±0.3 respectively (P< 0.001). A second clinical study was performed in 25 patients studied by stress/rest ECG-gated SESTAMIBI scintigraphy. The assumption of this part of the study was to investigate if a preserved wall thickening in segments with stress defects might predict those areas with normal resting perfusion. Partial or total normalization of regional perfusion was observed in 90% of segments with a WTI0.8. These studies indicate the ECG-gated SESTAMIBI may represent a suitable technique for the simultaneous analysis of flow distribution and function. Analysis of post-exercise ECG-gated SESTAMIBI can predict the reversibility of transient perfusion defects.Abbreviations ECG electrocardiogram - SESTAMIBI Technetium-99 m methoxy-isobutyl-isonitrile - WTI wall thickening index     

Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis

Hemojuvelin (HJV) positively modulates the iron regulator hepcidin, and its mutations are the major cause of juvenile hemochromatosis (JH), a recessive disease leading to iron overload. Defective HJV reduces hepcidin up-regulation both in humans and in Hjv-deficient mice. To investigate the JH pathogenesis and the functional properties of human HJV we studied the biosynthesis and maturation of 6 HJV pathogenic mutants in HeLa and HepG2 cells. We show that proteolytic processing is defective in mutants F170S, W191C, and G320V, but not in G99V and C119F. Moreover, we show that mutants G99V and C119F are targeted to the cell surface, while F170S, W191C, G320V, and R326X (lacking the glycosilphosphatidylinositol [GPI] anchor) are mainly retained in the endoplasmic reticulum, although all mutants are released as soluble forms (s-HJV) in a proportion that is modulated by iron supplementation. Membrane HJV (m-HJV) is mainly composed of the cleaved protein, and its level is increased by iron in wild-type (WT) mice but not in the mutants. Altogether, the data demonstrate that the loss of HJV membrane export is central to the pathogenesis of JH, and that HJV cleavage is essential for the export. The results support a dual function for s- and m-HJV in iron deficiency and overload, respectively.     

Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population

A proinflammatory genotype seems to contribute significantly to the risk of developing coronary heart disease (CHD). Conversely, the susceptibility alleles to inflammatory disease should be infrequent in the genetic background favoring longevity. In fact, in a modern environment, attainment of longevity is facilitated by an anti-inflammatory status. To evaluate whether inflammatory alleles of pyrin, the gene responsible for familial Mediterranean fever (FMF) may play an opposite role in CHD and in longevity, we examined three FMF-associated mutations, M694V (A2080G), M694I (G2082A), and V726A (T2177C), encoded by the FMF gene (MEFV) in 121 patients affected by acute myocardial infarction (AMI), in 68 centenarians, and in 196 age-matched controls from Sicily. None of the Sicilian subjects studied carried the V726A and the M694I FMF-related mutations. The proinflammatory M694V (A2080G) mutation was the only one we found, which was over-represented significantly in CHD patients and under-represented in oldest old, and intermediate values were in healthy, young controls. After adjustment for well-recognized AMI risk factors, the M694V allele still predicted a significant risk to develop AMI. So, according to these results, we suggest that carrying the proinflammatory M694V pyrin allele may increase the risk to develop AMI. Conversely, the wild-type pyrin genotype may predispose to a greater chance to live longer in a modern environment with reduced pathogen load and improved control of severe infections by antibiotics. All these data indicate a strong relationship among inflammation, genetics, CHD, and longevity.     

Mandibular implant-retained overdentures with 2 different prosthetic designs: a retrospective pilot study on maintenance interventions

This retrospective study aimed to investigate whether a mandibular implant-retained overdenture designed to counteract the rotation of the denture might influence the clinical outcome, as evaluated through the prosthetic maintenance interventions. The amount of repairs and relines of the mandibular and maxillary dentures required in an experimental group (6 patients wearing an implant-retained overdenture with a metal frame counteracting the rotation) and a control group (6 patients wearing an implant-retained overdenture allowing the rotation) was compared. Both mandibular and maxillary dentures needed few repairs or relines. The 2 types of dentures showed a similar number of maintenance interventions.     

Systematic review by meta-analyses on the possible role of TNF-α polymorphisms in association with Alzheimer's disease

It has been hypothesized that polymorphisms of Tumor Necrosis Factor (TNF)-α gene affect the risk of developing Alzheimer's disease (AD). However, results of different studies are often inconsistent. Our aim was to investigate by meta-analysis the association of the common polymorphisms comprehensively defining the genetic variability of the TNF-α gene with AD risk. Hence, the results being stated are of a meta-analysis across studies, and that this meta-analysis does not invalidate the results of the individual studies previously performed. Seventeen studies that investigated the association between 5 TNF-α polymorphisms (− 850, − 308, − 863, − 238, and − 1031) and AD were retrieved and analyzed. The model-free approach was applied to meta-analyze these case-control genetic association studies. Available data suggested a significant association between − 850 polymorphism and AD risk (TT vs. TC + CC: pooled odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08–2.29; p = 0.02) with no evidence of between-study heterogeneity (χ², p > 0.1). Subgroup analysis suggested that the possession of T allele significantly increased the risk of AD associated with carriage of the apolipoprotein E 4 allele in Caucasian Australians and Northern Europeans (TT + TC vs. CC: OR, 1.95; 95% CI, 1.45–2.62; p = 0.00001; p > 0.1; χ² for heterogeneity, p > 0.1). No significant difference in genotype distribution of − 308 polymorphism in AD was found, with a high degree of between-study heterogeneity. For the − 863 and − 1031 polymorphisms we did not find an association with AD, but significant between-study heterogeneity discouraged genotype data pooling. Only four studies investigated the − 238 variant and the results were not significant. Current findings support an association between − 850 C > T polymorphism and the risk of developing AD; hence, they strengthen the suggestion of a potential role for anti-TNF therapy to maintain physiologic levels of TNF-α.