Prediction Models for Cardiac Risk Classification with Nuclear Cardiology Techniques

Regression modeling strategies are increasingly used for the management of subjects with cardiovascular diseases as well as for decision-making of subjects without known disease but who are at risk of disease in the short- or long-term or during life span. Accurate individual risk assessment, taking in account clinical, laboratory, and imaging data is useful for choosing among prevention strategies and/or treatments. The value of nuclear cardiology techniques for risk stratification has been well documented. Many models have been proposed and are available for diagnostic and prognostic purposes and several statistical techniques are available for risk stratification. However, current approaches for prognostic modeling are not perfect and present limitations. This review analyzes some specific aspects related to prediction model development and validation

Genetic deletion in uncoupling protein 3 augments 18F-fluorodeoxyglucose cardiac uptake in the ischemic heart

BACKGROUND: We investigated the effects of uncoupling protein 3 (UCP3) genetic deletion on 18F-fluorodeoxyglucose (FDG) cardiac uptake by positron emission tomography (PET)/computed tomography (CT) dedicated animal system after permanent coronary artery ligation. METHODS: Cardiac 18F-FDG PET/CT was performed in UCP3 knockout (UCP3-/-) and wild-type (WT) mice one week after induction of myocardial infarction or sham procedure. RESULTS: In sham-operated mice no difference in left ventricular (LV) volume was detectable between WT and UCP3-/-. After myocardial infarction, LV volume was higher in both WT and UCP3-/- compared to sham animals, with a significant interaction (p < 0.05) between genotype and myocardial infarction. In sham-operated animals no difference in FDG standardized uptake value (SUV) was detectable between WT (1.8 ± 0.6) and UCP3-/- (1.8 ± 0.6). After myocardial infarction SUV was significantly higher in remote areas than in infarcted territories in both UCP3-/- and WT mice (both p < 0.01). Moreover, in remote areas, SUV was significantly higher (p < 0.001) in UCP3-/- as compared to WT, while in the infarcted territory SUV was comparable (p = 0.29). A significant relationship (r = 0.68, p < 0.001) between LV volume and SUV was found. CONCLUSIONS: In a mice model of permanent coronary occlusion, UCP3 deficiency results in a metabolic shift that favored glycolytic metabolism and increased FDG uptake in remote areas

Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC

Effects of losartan treatment on cardiac autonomic control during volume loading in patients with DCM

This study evaluated the effect of angiotensin II receptor blockade on cardiac autonomic control adaptation and urine output in response to acute isotonic volume load in patients with idiopathic dilated cardiomyopathy (DCM) and asymptomatic to mildly symptomatic heart failure. Left ventricular volumes and heart rate variability measurements were assessed at baseline and during intravenous saline load in 14 patients before and after 2 mo of losartan treatment. After losartan treatment, blood pressure values were lower, whereas left ventricular ejection fraction was higher (F = 79, P50 ms) decreased during saline load in untreated patients (F = 3.1, P< 0.05 and F = 6.5, P< 0.01, respectively), but not after losartan. Similarly, a decrease in very low frequency (F = 3.2, P< 0.05), low-frequency (F = 2.9, P< 0.05), and high-frequency power (F = 6.1, P< 0.01) after saline load was observed only in untreated patients. In patients with DCM, losartan treatment improves the cardiac autonomic adaptation and increases urine output in response to volume overload

Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry's disease.

Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness

Total occlusion of the abdominal aorta in a patient with renal failure and refractory hypertension: a case report

Total occlusion of the abdominal aorta is unusual, and potentially catastrophic. It occurs in patients with advanced atherosclerotic occlusive disease, and can cause severe ischemic manifestations, depending on the site of obstruction. Prompt and appropriate diagnostic and therapeutic approaches are important whenever this condition is suspected, in order to avoid a fatal outcome. The development of a complex network of collaterals may prevent the manifestation of acute ischemic phenomena, and cause a delay in diagnosis and treatment. Here we report the clinical case of a 59-year-old man who was referred to our Department for evaluation of renal failure and refractory hypertension. Ultrasonography and 99mTc-DTPA scintigraphy showed a shrunken, non-functioning left kidney, while CT angiography and aortography showed the complete occlusion of the aorta from below the right renal artery down to the bifurcation of both common iliac arteries, with a critical stenosis of the origin of the right renal artery, an occlusion of the left renal artery as well as of the origin of the inferior mesenteric artery. The patient was referred to the surgery department for aorto-bifemoral bypass surgery and re-implantation of the right renal artery

The effect of iterative model reconstruction on coronary artery calcium quantification

Coronary artery calcium (CAC) scoring with computed tomography (CT) is an established tool for quantifying calcified atherosclerotic plaque burden. Despite the widespread use of novel image reconstruction techniques in CT, the effect of iterative model reconstruction on CAC score remains unclear. We sought to assess the impact of iterative model based reconstruction (IMR) on coronary artery calcium quantification as compared to the standard filtered back projection (FBP) algorithm and hybrid iterative reconstruction (HIR). In addition, we aimed to simulate the impact of iterative reconstruction techniques on calcium scoring based risk stratification of a larger asymptomatic population. We studied 63 individuals who underwent CAC scoring. Images were reconstructed with FBP, HIR and IMR and CAC scores were measured. We estimated the cardiovascular risk reclassification rate of IMR versus HIR and FBP in a larger asymptomatic population (n = 504). The median CAC scores were 147.7 (IQR 9.6-582.9), 107.0 (IQR 5.9-526.6) and 115.1 (IQR 9.3-508.3) for FBP, HIR and IMR, respectively. The HIR and IMR resulted in lower CAC scores as compared to FBP (both p < 0.001), however there was no difference between HIR and IMR (p = 0.855). The CAC score decreased by 7.2 % in HIR and 7.3 % in IMR as compared to FBP, resulting in a risk reclassification rate of 2.4 % for both HIR and IMR. The utilization of IMR for CAC scoring reduces the measured calcium quantity. However, the CAC score based risk stratification demonstrated modest reclassification in IMR and HIR versus FBP

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial)

BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery. Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care). The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction

Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties