Background-Depressed myocardial blood flow (MBF) has been reported in dilated cardiomyopathy. The aim of this study was to investigate whether MBF impairment is an independent predictor of prognosis in patients with idiopathic left ventricular (LV) dysfunction. Methods and Results-Sixty-seven patients (52 male, mean age 52Ϯ12 years) with different degrees of idiopathic LV systolic dysfunction (average LV ejection fraction, 0.34Ϯ0.10; range, 0.07 to 0.49) were prospectively enrolled. Thirty-four subjects (51%) had no history of heart failure symptoms at enrollment (NYHA class I). All patients underwent clinical and functional evaluation and a PET study to measure absolute MBF at rest and after intravenous dipyridamole. During a mean follow-up of 45Ϯ37 months, 24 patients had major cardiac events, including cardiac death in 8 and development or progression of heart failure in 16 patients. Multivariate regression analysis (Cox proportional hazards model) revealed heart rate ( 2 11.06, PϽ0.001), LV end-diastolic dimension ( 2 11.73, PϽ0.001), and dipyridamole MBF ( 2 11.04, PϽ0.001) as independent predictors of subsequent cardiac events. Dipyridamole MBF Յ1.36 mL ⅐ min Ϫ1 ⅐ g Ϫ1 was associated with an increase in the relative risk of death, development, or progression of heart failure of 3.5 times over other more common clinical and functional variables. Conclusions-The present study demonstrates that severely depressed MBF is a predictor of poor prognosis in patients with idiopathic LV dysfunction independently of the degree of LV functional impairment and of the presence of overt heart failure.

Background-The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results-A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74;

In patients with DCM without overt heart failure, myocardial perfusion is impaired both at rest and in response to vasodilating stimuli. The abnormalities in vasodilating capability can be present despite normal hemodynamics; progression of the disease is associated with more depressed myocardial perfusion.

To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

A, Stanley WC, Recchia FA. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 293: H3270-H3278, 2007. First published October 5, 2007; doi:10.1152/ajpheart.00887.2007.-Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [ 3 H]oleate and [ 13 C]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization. microcirculation FATTY ACIDS provide 60 -90% of the energy necessary to sustain contractile function in the resting fasting state, with the remainder coming from glucose and lactate oxidation. During acute cardiac stress, such as pacing or exercise, the healthy human heart rapidly increases glucose and lactate uptake, with a relative decline in free fatty acid (FFA) uptake (1,3,4,9). Clinical and animal studies have suggested that this response is advantageous: it increases myocardial metabolic efficiency, since carbohydrates are a more efficient substrate than lipids, generating more contractile power for any given rate of myocardial oxygen consumption (MV O 2 ) (20,29,31).Dilated cardiomyopathy (DCM) is often characterized by reduced FFA uptake and oxidation and accelerated glycolysis and glucose oxidation under resting conditions (7,21,31). This metabolic shift may act to optimize the limited oxidative capacity of cardiomyopathic hearts resulting from impairment of mitochondrial function (28) and/or ATP transfer from ...

Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to explain these changes. This is a heterogeneous disease frequently having a genetic background. Imaging is important for the diagnosis, the prognostic assessment and for guiding therapy. A multimodality imaging approach provides a comprehensive evaluation of all the issues related to this disease. The present document aims to provide recommendations for the use of multimodality imaging according to the clinical question. Selection of one or another imaging technique should be based on the clinical condition and context. Techniques are presented with the aim to underscore what is ‘clinically relevant’ and what are the tools that ‘can be used’. There remain some gaps in evidence on the impact of multimodality imaging on the management and the treatment of DCM patients where ongoing research is important.

Transient reduction in coronary perfusion pressure in the isolated mouse heart increases microvascular resistance (paradoxical vasoconstriction) by an endothelium-mediated mechanism. To assess the presence and extent of paradoxical vasoconstriction in hearts from normal and diabetic rats and to determine whether increased heme oxygenase (HO)-1 expression and HO activity, using cobalt protoporphyrin (CoPP), attenuates coronary microvascular response, male Wistar rats were rendered diabetic with nicotinamide/streptozotocin for 2 wk and either CoPP or vehicle was administered by intraperitoneal injection weekly for 3 wk (0.5 mg/100 g body wt). The isolated beating nonworking heart was submitted to transient low perfusion pressure (20 mmHg), and coronary resistance (CR) was measured. During low perfusion pressure, CR increased and was associated with increased lactate release. In diabetic rats, CR was higher, HO-1 expression and endothelial nitric oxide synthase were downregulated, and inducible nitric oxide synthase and O(2)(-) were upregulated. After 3 wk of CoPP treatment, HO activity was significantly increased in the heart. Upregulation of HO-1 expression and HO activity by CoPP resulted in the abolition of paradoxical vasoconstriction and a reduction in oxidative ischemic damage. In addition, there was a marked increase in serum adiponectin. Elevated HO-1 expression was associated with increased expression of cardiac endothelial nitric oxide synthase, B-cell leukemia/lymphoma extra long, and phospho activator protein kinase levels and decreased levels of inducible nitric oxide synthase and malondialdehyde. These results suggest a critical role for HO-1 in microvascular tone control and myocardial protection during ischemia in both normal and mildly diabetic rats through the modulation of constitutive and inducible nitric oxide synthase expression and activity, and an increase in serum adiponectin.

Arrhythmogenic cardiomyopathy (AC) is a progressive disease with high risk of life-threatening ventricular arrhythmias. A genetic mutation is found in up to 50-60% of probands, mostly affecting desmosomal genes. Diagnosis of AC is made by a combination of data from different modalities including imaging, electrocardiogram, Holter monitoring, family history, genetic testing, and tissue properties. Being a progressive cardiomyopathy, repeated cardiac imaging is needed in AC patients. Repeated imaging is important also for risk assessment of ventricular arrhythmias. This expert consensus document gives clinical recommendations for how to use multi-modality imaging in the different aspects of AC disease, including diagnosis, family screening, follow-up, risk assessment, and differential diagnosis.