Nonischemic Origin Research Articles

Endothelial Function and Arterial Compliance are not Impaired in Subjects With Heart Failure of Non-Ischemic Origin

BackgroundPatients with heart failure and underlying ischemic heart disease (IHD) exhibit both endothelial dysfunction and increased arterial stiffness. We investigated whether this is also the case in heart failure of nonischemic etiology. Methods and ResultsEleven patients with heart failure and IHD, 12 patients with heart failure from angiographically verified idiopathic nonischemic dilated cardiomyopathy (DCM), and 16 healthy subjects of similar age and sex were compared. Endothelium-dependent and independent function were evaluated by ultrasonic measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-induced dilatation of the brachial artery respectively. Vascular compliance was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx). Heart failure severity was similar in IHD and DCM patients. FMD was impaired in the subjects with IHD as compared with control subjects (4.8 ± 0.3 vs. 8.0 ± 3.6 %, P < .01), but not in those with DCM. GTN-induced vasodilatation was not different in patients and controls. PWV was also increased in IHD patients compared with controls (12.1 ± 3.6 vs. 8.0 ± 1.6 m/s, P < .01), but not in DCM patients. AIx was similar in patients and controls. ConclusionHeart failure of nonischemic etiology is not associated with abnormalities of endothelium-mediated dilatation or of arterial compliance. The findings of our study now need to be confirmed in larger studies.

The C-Reactive Protein Levels in Left Ventricular Dysfunction of Different Etiology

We have investigated variations in the C-reactive protein levels in groups of patients with left ventricular dysfunction of various causes. We have studied 59 patients (ranging from 40 to 80 years, mean age of 64, SD 9) with left ventricular dysfunction caused by dilated cardiomyopathy, valvular heart disease, chronic ischemic cardiomyopathy. These patients have been compared to 30 healthy subjects and to 15 others with acute myocardial infarction. The C-reactive protein levels have been analyzed and correlated to echocardiographic index of the left ventricular function as well as to the clinical parameters. The levels of C-reactive protein show a statistically significant difference between healthy controls and patients with chronic left ventricular dysfunction (0.95mg/l +-0.9 vs 10.17+-13.77; p <0.0001); a statistically significant difference between patients with chronic left ventricular dysfunction and patients with acute myocardial infarction (10.17mg/l+-13.7 vs 30.78+-22.53, p<0.0001), and a statistically significant difference between the group of patients with chronic left ventricular dysfunction of both ischemic and non ischemic origin (15.39mg/l +-18.19 vs 6.83+-8.77, p = 0.0095). When all chronic patients were analyzed together, the levels of C-reactive protein correlated with the New York Heart Association class (r = 0.282, p = 0.015), age (r = 0.231, p = 0.039) and with the end diastolic volume of left ventricle (r = -0.230, p = 0.040). As shown by increment of C-reactive protein values, the immune system is activated in patients with the chronic left ventricular dysfunction. The patients with the chronic left ventricular dysfunction of an ishemic origin have higher levels of C-reactive protein than those of a non-ischemic origin. This difference could depend on the atherosclerotic process present presumably only in the first group.

Cardiomyopathy and the dilemma of geometric mitral regurgitation

Geometric mitral regurgitation is a phenomenon encountered by an otherwise anatomically normal mitral valve in the setting of advanced adverse left ventricular remodeling that alters the alignment characteristics of the mitral valve apparatus leading to functional production of a leaking valve. In this review, we discuss contemporary directions in the knowledge base for managing geometric mitral regurgitation. Much progress has been encountered in describing the types of geometric mitral regurgitation (nonischemic and ischemic origins), standardization of echocardiographic techniques to allow for a common language in ascertaining the severity of mitral regurgitation, knowledge on dynamic mitral regurgitation during exercise, effectiveness of therapy and appropriate use and timing of surgical repair. Geometric mitral regurgitation develops in tandem with progressive ischemic or nonischemic cardiomyopathy and can improve with antiremodeling pharmacological and device-based therapy. Surgical therapy can be accomplished at experienced centers with low morbidity and mortality, and may improve symptoms and enhance pump function. Whether such therapy saves lives remains uncertain. New percutaneous approaches to tackle geometric mitral regurgitation are developing, and early data is encouraging but remains experimental.

Abstract 3051: Percutaneous Repair of Functional Mitral Regurgitation Using CARILLON ™ Mitral Contour System. Acute Transesophageal Echocardiography Results from AMADEUS ™ Trial

Left ventricular dilatation with subsequent mitral insufficiency exacerbates heart failure. New techniques for percutaneous repair of Functional Mitral Regurgitation (FMR) are being developed to minimize the high procedural risk of conventional cardiac surgery therapies. To evaluate the feasibility and procedural safety of percutaneous mitral valve repair with CARILLON ™ Mitral Contour System ™ (Cardiac Dimensions® Inc.) in FMR patients AMADEUS ™ trial has been designed. Patients with FMR of both ischemic and non-ischemic origin were enrolled to this multicenter phase I trial. The device is implanted into the coronary venous system and applies tension to the mitral ring in order to improve coaptation of the leaflets. Transesophageal echocardiography (TEE) was used to assess the MR changes. Acute procedural data, obtained in the cath lab immediately before and after the procedure, are reported. Percutaneous mitral annuloplasty in patients with FMR and dilated cardiomyopathy resulted in acute MR reduction (grade 3.0±0.6 to 2.0±0.8, p&lt;0.0001) and permanent device implantation in 30 out of 43 attempts. Additional measurements in final 20 implanted patients showed reductions in vena contracta (0.69±0.29 cm to 0.46±0.26 cm, p&lt;0.0001), effective regurgitant orifice area (0.33±0.17 cm 2 to 0.19±0.08 cm 2 , p&lt;0.0001), regurgitant volume (40±20 ml to 24±11 ml, p= 0.0005), and jet area/left atrial area (45±13% to 32±12%, p&lt;0.0001). Coronary arteries were crossed in 36 patients (84%), but arterial compromise contributed to lack of implantation in 6 patients (14%). All unsuccessful implants were recaptured and removed in these patients without procedural complications. Permanent implantation of the device is safely achievable in the majority of eligible patients resulting in acute MR reduction. Arteries are crossed in most patients and without significant impact. Phase two trials including long term clinical observations on larger number of patients are needed to asses the clinical value of the technique.

Survival trends in men and women with heart failure of ischaemic and non-ischaemic origin: data for the period 1987-2003 from the Swedish Hospital Discharge Registry

To investigate gender-specific trends in long-term mortality in patients hospitalized for heart failure (HF). The Swedish hospital discharge and cause-specific death registers were used to calculate age- and gender-specific trends for long-term prognosis in patients hospitalized with a principal diagnosis of HF from 1987 to 2003. Mortality decreased, mainly during 1987-95, with no further decrease after 2001. Survival in men improved more than in women (P-value for interaction 0.0003), particularly among patients aged <65 years (P-value for interaction: age, gender, and year of hospitalization 0.0003) and more for patients with ischaemic when compared with non-ischaemic HF (P-value for interaction <0.0001). Among men <65 years, the hazard ratio (HR) of dying within 3 years after discharge was 0.40 (95% confidence interval 0.36-0.45) during 1999-2001 when compared with 1987-89. The corresponding HR for women was 0.58 (0.48-0.69). For those discharged during 1999-2001, almost 20% of the patients aged 35-64 years and 40% of those aged 65-84 years died within 3 years. Long-term mortality in HF in Sweden decreased more for men than for women and more for ischaemic than non-ischaemic HF. There was no further decrease after 2001. Long-term mortality after a first hospitalization remained high.

Lack of Diurnal Variation of P‐Wave and QT Dispersions in Patients with Heart Failure

P-wave dispersion (PWD) is a new parameter for the assessment of risk of atrial fibrillation and has been reported to be increased in heart failure. Diurnal variation of the PWD has been reported in patients with coronary artery disease (CAD). QT dispersion (QTD) has also a circadian variation. In this study we aimed to search diurnal variation of PWD and QTD in patients with heart failure. Fifty-three clinical heart failure patients having left ventricular ejection fraction (LVEF) <40% were divided into two groups according to presence of CAD. Twelve-lead ECGs were obtained in the morning (07:00-08:00 hours), at noon (12:00-14:00 hours), and at night (22:00-24:00 hours). All the patients were in New York Heart Association class II except one in class I. beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker usage was over 80% and spiranolactone usage was around 75% in the study group. PWD and QTD were not significantly different between patients with (n = 27) and without (n = 26) CAD. There was no significant diurnal variation of P wave and QT parameters. We found that PWD and QTD do not show diurnal variation in patients having either ischemic or nonischemic origin of heart failure treated with optimal drug therapy.

Transient Ischemic Attack Etiologic Subtype and Early Risk of Stroke

To the Editor: Although clinical features help stratify stroke risk after transient ischemic attack (TIA), the novel study by Purroy et al1 on predictors of early recurrent ischemia according to etiologic subtype of the index TIA emphasizes additional variables we must consider in our prognostication algorithms. We wish to discuss some issues raised in the article which we felt merited further exploration. The study found a very low recurrent event rate in the small-vessel disease (SVD) group (1.5%, or 1 event/68 patients). Transient lacunar events due to SVD are commonly thought to have a relatively benign prognosis, and these results support such an assertion. However, in our experience, lacunar events can often progress after a seemingly transient onset, and others have shown that lacunar …

Interleukin-13 Protects Against Experimental Autoimmune Myocarditis by Regulating Macrophage Differentiation

We report here that interleukin (IL)-13 protects BALB/c mice from myocarditis, whether induced by peptide immunization or by viral infection. In contrast to mild disease in IL-4 knockout (KO) BALB/c mice, IL-13 KO BALB/c mice developed severe coxsackievirus B3 (CVB3)-induced autoimmune myocarditis and myocarditogenic peptide-induced experimental autoimmune myocarditis. Such severe disease was characterized by increased cardiac inflammation, increased total intracardiac CD45(+) leukocytes, elevated anti-cardiac myosin autoantibodies, and increased cardiac fibrosis. Echocardiography revealed that IL-13 KO mice developed severe dilated cardiomyopathy with impaired cardiac function and heart failure. Hearts of IL-13 KO mice had increased levels of the proinflammatory and profibrotic cytokines IL-1beta, IL-18, interferon-gamma, transforming growth factor-beta1, and IL-4 as well as histamine. The hallmark of the disease in IL-13 KO mice was the up-regulation of T-cell responses. CD4(+) T cells were increased in IL-13 KO hearts both proportionally and in absolute number. Splenic T cells from IL-13 KO mice were highly activated, and myosin stimulation additionally increased T-cell proliferation. CD4(+)CD25(+)Foxp3(+) regulatory T-cell numbers were decreased in the spleens of IL-13 KO mice. IL-13 deficiency led to decreased levels of alternatively activated CD206(+) and CD204(+) macrophages and increased levels of classically activated macrophages. IL-13 KO mice had increased caspase-1 activation, leading to increased production of both IL-1beta and IL-18. Therefore, IL-13 protects against myocarditis by modulating monocyte/macrophage populations and by regulating their function.

Increased adiponectin level in parallel with increased NT-pro BNP in patients with severe heart failure in the elderly: A hospital cohort study

Background Adiponectin, which is a collagen-like plasma protein produced by adipose tissue, has in general anti-atherogenic and anti-inflammatory effects. Recently it was shown to be elevated in chronic heart failure patients. However whether this holds true in the elderly heart failure patients who are often associated with malnutrition remains unknown. Materials and methods Patients with severe heart failure ( n = 92, average age > 70 years, NYHA III–IV) and age-matched healthy volunteers ( n = 70) as control were enrolled in the present study. Serum levels of adiponectin and NT-pro BNP were measured. Results Adiponectin levels were significantly increased in heart failure patients for those > 70 years old as compared with control group. There were higher adiponectin levels in non-ischemic heart failure as compared with those with ischemic cause. Serum adiponectin levels were positively associated with serum NT-pro BNP levels. There was a strong trend of higher adiponectin levels in those who died as compared with those who survived. Conclusion Serum adiponectin levels were increased in the very elderly heart failure patients, and particularly in those with underlying non-ischemic origin. Adiponectin levels appear to be associated with increased mortality.

Troponin-T Monitoring in Outpatients With Nonischemic Heart Failure

The usefulness of prolonged troponin-T (TnT) monitoring in outpatients with nonischemic heart failure (HF) is not clear. The aim of this study was to investigate the incidence, prognostic value and determinants of a raised TnT level. The study involved 80 outpatients (age 56+/-14 years, 69% male) with chronic stable HF (mean left ventricular ejection fraction 24+/-9%; 51 in New York Heart Association class II and 29 in class III) of non-ischemic origin, as confirmed with coronary angiography. The TnT level was measured at study entry and at every outpatient visit (median interval, 3.1 months; interquartile range [IQR], 1.8-5.0 months) in a follow-up period of 22.2+/-10.6 months. Patients were TnT+ if the level was measurable (i.e., >0.01 ng/mL). At study entry, 7 (9%) patients were TnT+. By 5 years, the cumulative incidence had reached 53%, and the median TnT level was 0.059 ng/mL (IQR, 0.023-0.100 ng/mL; range, 0.013-0.500 ng/mL). Beta-blocker therapy was associated with a reduction in incidence (hazard ratio [HR]=0.220; 95% confidence interval [CI], 0.089-0.540; P=.001) while the incidence increased with the N-terminal probrain natriuretic peptide (NT-proBNP) level (HR=1.005; 95% CI, 1.001-1.010; P=0.021). During follow-up, 14 (17.5%) patients had a cardiac event (i.e., 9 cardiac deaths and 5 urgent transplants); these occurred in 12 (50%) of the 24 TnT+ patients vs. 2 (3.6%) of the 56 TnT- patients (P< .001). After adjustment, Cox multivariate analysis showed that being TnT+ was a predictor of an adverse event (HR per 0.01 ng/mL=1.359; 95% CI, 1.037-1.782; P=.026), independently of the NT-proBNP level (HR per 500 pg/mL=1.057; 95% CI, 1.023-1.092; P=.001). A measurable TnT level was frequently observed during clinical monitoring of outpatients with non-ischemic HF and indicated a poor prognosis, even when the level was low.

Abstract 1769: Multidetector Computed Tomography allows accurate non-invasive Diagnosis of Etiology of Heart failure as compared with Coronary Angiography and contrast-enhanced MRI

Background: The distinction of ischemic vs. non-ischemic origin is essential for prognosis and treatment of patients (pts) with congestive heart failure (CHF). To determine etiology, pts typically undergo invasive coronary angiography (CA). Additional information can be obtained by detecting necrosis or fibrosis on delayed enhanced (DE) magnetic resonance (cMR). Recently, we and others have demonstrated that detection of myocardial necrosis is also feasible by multidetector CT (MDCT) at the time of non-invasive coronary imaging. We therefore evaluated whether such a combined and comprehensive evaluation of coronary anatomy and infarct characterization by MDCT might be useful for determining the etiology of CHF. Methods: Sixty-one consecutive pts (44 males, 60 ± 16 years) with CHF (mean ejection fraction: 26 ± 11%) of undetermined etiology underwent MDCT, DE-MR and CA. Presence of coronary artery disease (CAD) and patterns of DE on MDCT were compared to CA and DE-MR. Results: According to CA, 27 pts (44%) had significant CAD (&gt;50% stenosis in at least one major coronary artery). DE-cMR demonstrated transmural or subendocardial DE in 21 of these 27 pts. These 21 pts were considered to have definite ischemic CHF (group 1). Among the 34 pts without CAD on CA, 23 had no DE on cMR, while 7 (11%) presented midventricular or sub-epicardial DE. These 30 pts were considered to have definite non-ischemic CHF (group 2). Four pts had transmural DE but no CAD and were considered to have probable ischemic CHF (group 3). Finally, 6 pts with CAD on CA, but without DE on cMR were considered to have probable non-ischemic CHF (group 4). Pts were also classified into the same 4 groups using coronary and DE-MDCT. On a per patient basis, agreement between coronary and DE-MDCT and CA/DE-cMR for the diagnosis of patients was excellent (κ=0.87; p&lt;0.001). Coronary and DE-MDCT had 96% sensitivity, 92% specificity and 93% accuracy for detecting definite (group 1) or probable (group 3) ischemic CHF as compared to DE-cMR and CA. Conclusion: Combined coronary and DE-MDCT allows for the accurate differentiation of ischemic vs non ischemic etiology of CHF as compared to CA and DE-cMR. Using this single test is however cheaper and faster than combined use of DE-cMR and CA for establishing etiology of CHF.

Human cardiac stem cells

The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin.

Activation of polymorphonuclear neutrophils in patients with impaired left ventricular function

Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single-center study. In 113 patients with impaired left ventricular function (ejection fraction < 50%; nonischemic cardiomyopathy, n = 52; ischemic cardiomyopathy, n = 61), MPO plasma levels were elevated (24.5 [IR:15.8–54.0] vs 15.5 [IR:8.9–39.2] ng/ml in controls, P < 0.01) as was elastase (111.5 [IR:63.8–233.3] vs 70.5 [IR:45.0–129.0] ng/ml, P < 0.01) and NT-proBNP plasma levels (747.4 [IR:216.3–1958.3] vs 264.1 [IR:82.5–671.8] ng/L, P < 0.01). Elevation of circulating MPO was irrespective of the etiology of heart failure and independent of traditional confounding variables. No association was observed between MPO −463 promoter polymorphism genotype and LV dysfunction. MPO plasma levels correlated with ejection fraction ( P < 0.01) and left ventricular end-diastolic diameter ( P < 0.01), respectively. Myeloperoxidase mRNA expression levels obtained from circulating leukocytes were significantly increased in patients with LV dysfunction. Systemic leukocyte activation with increased transcription of MPO mRNA and augmented release of MPO appears to represent a so far underrecognized characteristic in LV dysfunction, which was revealed to be irrespective of the underlying pathology. Given its potent proinflammatory properties, MPO may represent an important mechanistic link to LV dysfunction and deserves to be evaluated as both marker and therapeutic target in this disease.

Micronutrients in African-Americans with decompensated and compensated heart failure

Heart failure is thought to be more common and of greater severity in African-Americans (AAs). Potential mechanisms remain uncertain. The importance of micronutrient deficiencies in the pathophysiologic expression of congestive heart failure (CHF) in AAs remains to be explored, including hypovitaminosis D, which can promote secondary hyperparathyroidism (SHPT), together with hypozincemia and hyposelenemia, the 2 most crucial trace minerals integral to diverse biologic functions. Serum parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), Zn, and Se were monitored in 30 AAs hospitalized during June through December 2005, with decompensated failure and reduced ejection fraction (EF) (<35%) of predominantly nonischemic origin treated with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), furosemide, and spironolactone. Based on their symptomatic status before hospitalization, 15 patients were stratified as having protracted (>or=4 weeks) CHF, whereas 15 patients had short-term (1-2 weeks) CHF. These hospitalized patients were compared with 10 AA outpatients with stable, similarly treated compensated failure and comparable EF, and 9 AA normal volunteers without cardiovascular disease. Serum PTH was elevated in all patients with protracted CHF and in 60% of patients with short-term CHF, but not in compensated patients or normal volunteers. However, serum 25(OH)D was reduced in all patients with >or=4 weeks and 80% with either 1-2 weeks CHF or compensated failure compared with volunteers. Serum Zn was below normal in 11 of 15 patients with protracted CHF, in 8 of 15 patients with shorter duration CHF, and in 5 of 10 patients with compensated failure. Serum Se was reduced in all patients with >or=4 weeks, 60% with short-term CHF, and 90% of compensated patients. Concomitant to hypovitaminosis D, hypozincemia, and hyposelenemia, SHPT is a covariant of CHF in housebound AAs.

Effect of Timed Semirecumbency and Furosemide Dosing on Urinary Sodium Excretion in Patients with Compensated Heart Failure

The management of chronic cardiac failure, a salt-sensitive state, frequently includes administration of a loop diuretic to enhance urinary Na excretion. We hypothesized that a period of timed semirecumbency (vis-à-vis upright posture) would enhance the natriuresis that accompanies oral furosemide dosing in patients with compensated cardiac failure. Four ambulatory patients with compensated chronic cardiac failure (NYHA Class III) of ischemic and nonischemic origin and systolic dysfunction (ejection fraction <35%), who were receiving a stable regimen of oral furosemide and angiotensin-converting enzyme inhibitor, were enrolled into the study. In the institution's Clinical Research Center, we monitored and compared urine flow rate (mL/min) and Na excretion rate (mEq/hr) in each patient in response to two different protocols. Protocol 1 consisted of an initial 90-minute period of bedrest followed by the patient's oral furosemide dose and 180 minutes of upright activity and a subsequent 90-minute period of bedrest. Protocol 2 was similar, with the exception that furosemide dosing was given after upright activity and immediately prior to the second period of bedrest. With each patient serving as his or her own control, both urine flow rate and urinary Na excretion rate were markedly increased when furosemide was given prior to bedrest as compared to its dosing prior to upright activity. In patients with compensated chronic cardiac failure, the natriuresis that accompanies oral furosemide dosing is enhanced when given just prior to a period of timed semirecumbency. This approach represents a more optimal use of this loop diuretic in patients with compensated heart failure.

Cardiac Stem Cells and Mechanisms of Myocardial Regeneration

This review discusses current understanding of the role that endogenous and exogenous progenitor cells may have in the treatment of the diseased heart. In the last several years, a major effort has been made in an attempt to identify immature cells capable of differentiating into cell lineages different from the organ of origin to be employed for the regeneration of the damaged heart. Embryonic stem cells (ESCs) and bone marrow-derived cells (BMCs) have been extensively studied and characterized, and dramatic advances have been made in the clinical application of BMCs in heart failure of ischemic and nonischemic origin. However, a controversy exists concerning the ability of BMCs to acquire cardiac cell lineages and reconstitute the myocardium lost after infarction. The recognition that the adult heart possesses a stem cell compartment that can regenerate myocytes and coronary vessels has raised the unique possibility to rebuild dead myocardium after infarction, to repopulate the hypertrophic decompensated heart with new better functioning myocytes and vascular structures, and, perhaps, to reverse ventricular dilation and wall thinning. Cardiac stem cells may become the most important cell for cardiac repair.

Myocardial Contrast Echocardiography for Distinguishing Ischemic From Nonischemic First-Onset Acute Heart Failure

Distinguishing ischemic from nonischemic origin in patients presenting with acute heart failure (AHF) not resulting from acute myocardial infarction has both therapeutic and prognostic implications. The aim of the study was to assess whether myocardial contrast echocardiography (MCE) can identify underlying coronary artery disease (CAD) as the cause of AHF. Fifty-two consecutive patients with AHF with no prior clinical history of CAD and no clinical evidence of acute myocardial infarction underwent resting echocardiography and MCE both at rest and after dipyridamole stress at a mean of 9+/-2 days after admission. All patients underwent coronary arteriography before discharge. Of the 52 patients, 22 demonstrated flow-limiting CAD (>50% luminal diameter narrowing). Sensitivity, specificity, and positive and negative predictive values of MCE for the detection of CAD were 82%, 97%, 95%, and 88%, respectively. Among clinical, ECG, biochemical, resting echocardiographic, and MCE markers of CAD, MCE was the only independent predictor of CAD (P<0.0001). Quantitative MCE demonstrated significantly (P<0.0001) lower myocardial blood flow velocity reserve in vascular territories subtended by >50% CAD (0.59+/-0.46) compared with patients with normal coronary arteries (1.99+/-1.00). However, myocardial blood flow velocity reserve in patients with no significant CAD was significantly (P=0.03) lower compared with control (2.91+/-0.41). Myocardial blood flow velocity reserve correlated significantly (P<0.0001) with increasing severity of CAD. MCE, which is a bedside technique, may be used to detect CAD in patients presenting with AHF without a prior history of CAD or evidence of acute myocardial infarction. Quantitative MCE may further risk-stratify patients with AHF but no CAD.

Nonsustained ventricular tachycardia in dilated cardiomyopathy

In patients with structural heart disease, ventricular arrhythmias are associated with an increased risk of overall mortality and sudden cardiac death (SCD). Nonsustained ventricular tachycardia (NSVT) is common in patients with dilated cardiomyopathy of both ischemic and nonischemic origin. Recent studies suggest that NSVT may be a marker, but not a significant predictor, of mortality and SCD in that suppression of NSVT in these patients using antiarrhythmic drugs is of questionable benefit. Additionally, indications for implantable cardioverter defibrillator implantation do not include NSVT. This article focuses on the prognostic significance and treatment of patients with NSVT and ischemic or nonischemic dilated cardiomyopathy.

A direct comparison of the natriuretic peptides and their relationship to survival in chronic heart failure of a presumed non‐ischaemic origin

The natriuretic peptides have been validated as sensitive and specific markers of left ventricular dysfunction; brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NT-proANP) and N-terminal brain natriuretic peptide (NT-proBNP) elevations have been associated with New York Heart Association (NYHA) Class I-IV heart failure. We directly compared the association of each of these markers with 1-year survival in 173 patients with chronic heart failure of a presumed nonischaemic origin entering the PRAISE-2 Trial, a clinical study which assessed the therapeutic effect of Amlodipine in patients with NYHA Class III and IV heart failure and a left ventricular ejection fraction (LVEF) <30%. BNP, NT-proBNP, and NT-proANP levels were all correlated with 1-year mortality by univariate Cox proportional hazards analyses. With respect to multivariate Cox proportional hazards regression models containing variables deemed significant in univariate analyses, NT-proANP alone was identified as an independent predictor of 1-year mortality when log-transformed continuous covariates were utilized in the analysis. When the analysis was repeated using dichotomous covariates, NT-proANP remained the most significant predictor of 1-year mortality, followed by NT-proBNP, NYHA classification and BNP. We conclude that all three natriuretic peptides are significant predictors of short-term mortality in subjects with chronic congestive heart failure (CHF) of a presumed nonischaemic origin. Larger prospective studies are required to validate the clinical utility of NT-proANP as a discriminating marker of short-term survival, and to validate proposed cutoffs of approximately 2300 pmol/l for NT-proANP, 1500 pg/ml for NT-proBNP, and 50 pmol/l for BNP as prognostic indicators of adverse short-term outcome.

Early brain natriuretic peptide increase reflects acute myocardial ischemia in patients with ongoing chest pain

Background: Plasma brain natriuretic peptide levels increase during acute ischemic events. In this study we tested the diagnostic performance of brain natriuretic peptide measurements in the detection of acute myocardial ischemia. Methods: Blood brain natriuretic peptide was measured in 101 patients with ongoing chest pain but no heart failure or an ST-segment elevation myocardial infarction on arrival at the emergency department (baseline) and at 2 and 6 h later. After diagnostic testing and 1-month follow-up for ischemia, patients were classified as either ischemic or non-ischemic. Results: In the ischemic group median (25th, 75th percentiles) brain natriuretic peptide values (pg/ml) were 122 (20, 349) at baseline, 116 (36, 347) at 2 h, increasing to 148 (52, 428) at 6 h ( p<0.001 vs. baseline). Non-ischemic patients had 12 (5, 32) at baseline, 9 (6, 30) at 2 h, and 13 (5, 29) at 6 h ( p<0.001 vs. corresponding values of the ischemic group). Receiver operator characteristic curves were constructed for brain natriuretic peptide values at baseline 2 and 6 h and for the increase of peptide levels from baseline to 6 h. All areas under curve indicated a significant diagnostic ability for the detection of ischemia. The 6-h measurement had better diagnostic performance than baseline and 2-h measurements. The subgroup of ischemic patients without myocardial necrosis also had higher brain natriuretic peptide values and could thus be discriminated from non-ischemic subjects. Conclusions: Brain natriuretic peptide values may detect acute myocardial ischemia in patients with ongoing chest pain but without ST-segment elevation, and distinguish ischemic patients from those with pain of non-ischemic origin.