A second look with prone SPECT myocardial perfusion imaging reduces the need for angiography in patients at low risk for cardiac death or MI.

BACKGROUND: Correction for soft tissue signal attenuation can improve the diagnostic accuracy of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The aim of this study was to correlate SPECT-MPI findings with clinical outcomes in patients who underwent stress imaging in the supine position, who also underwent "second look" stress imaging in the prone position. METHODS: Patients without perfusion abnormalities were considered Normal (N = 270). Those with apparent supine stress perfusion abnormalities which all resolved during prone imaging formed the Normal-Prone group (N = 309). Patients with matched perfusion abnormalities during both supine and prone stress imaging were considered Abnormal (N = 169). RESULTS: During follow-up (187 ± 96 days), utilization rates for invasive coronary angiography were similar for Normal vs Normal-Prone patients (3.5% vs 3.8%; P = NS), but were significantly higher in Abnormal patients (42.4%, P < .0001). Coronary revascularization occurred in 0.78%, 0.64%, and 17.7% of Normal, Normal-Prone, and Abnormal patients, respectively (P < .001). Cardiac death or myocardial infarction occurred in 2.2%, 2.3%, and 6.3% of Normal, Normal-Prone, and Abnormal patients, respectively (P = .02). CONCLUSIONS: Second look SPECT-MPI identifies patients at low risk for death or myocardial infarction, who infrequently require invasive coronary angiography.

Diastolic heart failure: the current understanding and approach for management with focus on intensive care unit patients.

Multiple recent epidemiologic studies have highlighted the importance of diastolic heart failure (DHF) as a public health problem. Approximately half of patients presenting with symptomatic heart failure (HF) have DHF and they suffer from morbidity and mortality comparable to those with systolic HF. Our understanding of the pathophysiology of DHF has evolved rapidly over the last decade, and the associated echo-Doppler findings that assist with its diagnosis are greatly refined. Recently, there has been increased recognition of the role of diastolic dysfunction and DHF in the care of critically ill patients, including those admitted to noncardiac units. The purpose of this review is to provide an up-to-date summary of the concepts of the pathophysiology of DHF. In addition, we provide an overview of the diagnostic approaches, prognostic identifiers, and associated comorbidities that make DHF more resistant to manage with a focus of the patients admitted to the intensive care unit. The current approach to managing patients with DHF is also reviewed.

Coronary collateral circulation: its relevance.

The interest in coronary collateral circulation (CCC) as "natural bypasses" is growing, especially in patients in whom the extent of coronary atherosclerosis is too severe to allow for conventional revascularization. The anatomic foundation of CCC has been recognized for long time. Recently, reliable methods have become available for the assessment of the adequacy of collateral flow. However, the debate regarding the importance of CCC in the different clinical settings continues. In this article, we present the recent progress in the understanding of anatomy and physiology of the CCC and focus on the studies addressing their functional significance in acute, subacute, and chronic coronary artery disease. In addition, we provide a focused update on the essential role of collateral circulation in the management of coronary chronic total occlusions.

The Swan-Ganz catheters: past, present, and future. A viewpoint.

The Swan-Ganz balloon flotation catheter was introduced in 1970. It can be placed at the bedside within a few minutes even in critically ill patients. Although placement of these catheters is not difficult, some training and experience are required to avoid complications and for proper interpretation of the hemodynamic data that can be obtained by pulmonary artery catheterization. Because of the many advantages of balloon flotation catheters compared with conventional catheters, they have been used without a proper indication and frequently overused in critical care units, resulting in many complications, including mortality. The prospective randomized trials have reported that in the majority of clinical circumstances, the routine use of balloon flotation catheters is not indicated. These results are not surprising because balloon flotation catheters are diagnostic and not therapeutic tools. That we have learned a great deal about hemodynamics in critically ill patients with the use of balloon flotation catheters should not be ignored or forgotten. Furthermore, our clinical knowledge of hemodynamics has been made possible because of extensive experience gained from directly determined hemodynamics with the use of balloon flotation catheters. It should also be realized that despite the introduction and refinement of newer noninvasive imaging modalities, a number of clinical circumstances exist in which determination of hemodynamics with the use of a balloon flotation catheter is necessary and should be considered, but only by experienced physicians. With the proper use of Swan-Ganz catheters, our knowledge of hemodynamics has been enhanced considerably. Its abuse, particularly by relatively inexperienced operators, has resulted in serious complications, including death. Prospective randomized clinical trials have demonstrated that the routine use of Swan-Ganz catheters does not provide any benefit. However, use of the Swan-Ganz catheter is still indicated in many situations.

Prolonged therapy with erythropoietin is safe and prevents deterioration of left ventricular systolic function in a porcine model of myocardial infarction.

BACKGROUND: Erythropoietin (EPO) has generated interest as a novel therapy after myocardial infarction (MI), but the safety and efficacy of prolonged therapy have not been studied in a large animal model of reperfused MI. METHODS AND RESULTS: MI was induced in pigs by a 90-minute balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either EPO or saline (control group). Inflammatory markers, bone marrow cell mobilization, and left ventricular function (by both echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. EPO therapy was associated with a significant increase in hemoglobin and mononuclear counts. D-dimer and C-reactive protein levels did not differ between groups. At week 6, EPO therapy prevented further deterioration of left ventricular ejection fraction (39 +/- 2% vs. 33 +/- 1%, P < .01) and improved wall motion score index (P < .02). Histopathology revealed increased areas of viable myocardium, vascular density, and capillary-to-myocyte ratio in the EPO therapy compared with the control (all P < .05). CONCLUSION: Prolonged EPO therapy after MI in a large animal model is safe and leads to an increase in viable myocardium, increased vascular density, and prevents further deterioration of left ventricular function. These results support future clinical studies in post-MI patients.

Granulocyte colony stimulating factor in myocardial infarction with low ejection fraction.

BACKGROUND: We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia-reperfusion with left ventricle ejection fraction of <45% using a clinically relevant dosing and timing regimen. METHODS: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either GCSF (IV bolus of 10 microg/kg at time of reperfusion, followed by SC injections of 5 microg/kg days 5-9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. RESULTS: GCSF therapy was associated with a significant increase in white blood cell counts. At week 6, GCSF therapy resulted in less deterioration of LVEF compared to control (38+/-2% vs. 33+/-2%, p<0.02) and improved wall motion score index (p<0.05). Histopathology revealed increased vascular density (p<0.05) and a trend toward increased areas of viable myocardium compared to control (p=0.058). CONCLUSION: GCSF therapy prevents further deterioration of LV function in a porcine model of MI with lower EF (<45%). These results support future clinical trials with GCSF in selected patients with larger MI.

Vincristine attenuates N-methyl-N'-nitro-N-nitrosoguanidine-induced poly-(ADP) ribose polymerase activity in cardiomyocytes.

The DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) causes cardiomyocyte death as a result of energy loss from excessive activation of poly-(ADP) ribose polymerase-1 (PARP-1) resulting in depletion of its substrates nicotinamide adenine dinucleotide (NAD) and ATP. Previously we showed that the chemotherapeutic agent vincristine (VCR) is cardioprotective. Here we tested the hypothesis that VCR inhibits MNNG-induced PARP activation. Adult mouse cardiomyocytes were incubated with 100 micromol/L MNNG with or without concurrent VCR (20 micromol/L) for 2 to 4 hours. Cardiomyocyte survival was measured using the trypan blue exclusion assay. Western blots were used to measure signaling responses. MNNG-induced cardiomyocyte damage was time- and concentration-dependent. MNNG activated PARP-1 and depleted NAD and ATP. VCR completely protected cardiomyocytes from MNNG-induced cell damage and maintained intracellular levels of NAD and ATP. VCR increased phosphorylation of the prosurvival signals Akt, GSK-3beta, Erk1/2, and p70S6 kinase. VCR delayed PARP activation as evidenced by Western blot and by immunofluorescence staining of poly (ADP)-ribose, but without directly inhibiting PARP-1 itself. Known PARP-1 inhibitors also protected cardiomyocytes from MNNG-induced death. Repletion of ATP, NAD, pyruvate, and glutamine had effects similar to PARP-1 inhibitors. We conclude that VCR protects cardiomyocytes from MNNG toxicity by regulating PARP-1 activation, intracellular energy metabolism, and prosurvival signaling.

Doxorubicin cardiomyopathy.

Established doxorubicin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50%. Extensive research has been done to understand the mechanism and pathophysiology of doxorubicin cardiomyopathy, and considerable knowledge and experience has been gained. Unfortunately, no effective treatment for established doxorubicin cardiomyopathy is presently available. Extensive research has been done and is being done to discover preventive treatments. However an effective and clinically applicable preventive treatment is yet to be discovered.

Cytokine combination therapy with erythropoietin and granulocyte colony stimulating factor in a porcine model of acute myocardial infarction.

PURPOSE: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model. METHODS: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. RESULTS: At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p < 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy. CONCLUSION: Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF.

Coronary hemodynamics in heart failure and effects of therapeutic interventions.

BACKGROUND: The abnormalities in coronary hemodynamics in systolic heart failure are frequent. Myocardial oxygen demand and consumption are increased and myocardial perfusion is also impaired, which may result in myocardial ischemia, necrosis, and apoptosis. This is potentially a contributing factor for progressive heart failure. METHODS AND RESULTS: Neurohormonal abnormalities such as activated renin-angiotensin-aldosterone system, increased adrenergic activity, hemodynamic abnormalities such as decreased left ventricular perfusion pressure, and increased left ventricular diastolic pressure are important mechanisms for myocardial ischemia. CONCLUSIONS: Different pharmacologic agents may exert different effects on coronary hemodynamics although changes in systemic hemodynamics may be similar. Some agents may enhance myocardial ischemia and others may decrease it. Thus, an understanding of changes in coronary hemodynamics may have therapeutic implications.

Hyponatremia in heart failure.

Hyponatremia is one of the newer and emerging risk factors for an adverse prognosis in chronic heart failure. Why decreased serum sodium is associated with worse prognosis remains unclear. It may reflect worsening heart failure and the deleterious effects of activation of neurohormones. The mechanism of hyponatremia in heart failure also remains unclear. A relatively greater degree of free-water retention compared to sodium retention is probably the major mechanism. The treatment of significant hyponatremia in heart failure is difficult. The conventional treatments such as fluid restriction, infusion of hypertonic saline, and aggressive diuretic therapies are not usually effective. Vasopressin receptor antagonists have been shown to enhance aquaresis and correct hyponatremia. However, long-term beneficial effects of such treatments in chronic heart failure have not been documented.

Left ventricular remodeling after myocardial infarction: characterization of a swine model on beta-blocker therapy.

Current guidelines recommend beta blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a beta blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure-volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dt(max)), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential beta coefficient of the LV end-diastolic pressure-volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% +/- 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia-reperfusion swine model of acute MI on beta-blocker therapy and may guide future studies.

Vincristine attenuates doxorubicin cardiotoxicity.

Our aim was to test the hypothesis that the vinca alkaloid vincristine could prevent doxorubicin-induced cardiomyocyte death and to identify the mechanisms involved. Adult mouse cardiac myocytes were incubated for 24 h with doxorubicin, with and without concurrent vincristine. Trypan blue exclusion showed that 50-60% of myocytes treated with doxorubicin alone survived. Concurrent vincristine treatment increased survival to 85%. Treatment with doxorubicin+vincristine activated the prosurvival signal Akt and diminished cytochrome C release. The PI3K/Akt inhibitor LY294002 and the MEK/ERK inhibitor PD98059 augmented doxorubicin cardiotoxicity and attenuated salvage during concurrent vincristine treatment, indicating that the mechanism of vincristine cardioprotection involves activation of specific survival signals. Vincristine retarded the onset of apoptosis in association with a delay in poly(ADP) ribose polymerase activation. Vincristine also exhibited greater protection than the antioxidant MPG. These novel findings may have clinical implications for the prevention of doxorubicin cardiomyopathy.

Systolic heart failure: chronic and acute syndromes.

Systolic heart failure is characterized by ventricular dilation and reduced ejection fraction, and this syndrome may be either chronic or acute. Left ventricular remodeling is the principal cause of progression of systolic heart failure. Acute heart failure resulting from cardiomyopathy has similar functional and morphologic abnormalities. This review discusses remodeling, initial therapy based on neurohormonal modulation, and treatment of decompensated and refractory heart failure. Diagnosis, prognosis, and management of acute myocarditis are also discussed.

Systolic and diastolic heart failure: differences and similarities.

BACKGROUND: Diastolic heart failure (DHF) and systolic heart failure (SHF) are 2 clinical subsets of the syndrome of chronic heart failure that are most commonly encountered in clinical practice. METHODS AND RESULTS: The clinically overt DHF and SHF appear to be 2 separate syndromes with distinctive morphologic and functional changes although signs, symptoms, and prognosis are very similar. In DHF, the left ventricle is not dilated and the ejection fraction is preserved. In contrast in SHF, it is dilated and the ejection fraction is reduced. The neurohormonal abnormalities in DHF and SHF appear to be similar. The stimuli and the signals that ultimately produce these 2 different phenotypes of chronic heart failure remain, presently, largely unknown. CONCLUSIONS: Although there has been considerable progress in the management of SHF, the management of DHF remains mostly empirical because of lack of knowledge of the molecular and biochemical mechanisms which produce myocardial structural and functional changes in this syndrome. Further research and investigations are urgently required.

Diagnostic characteristics of combining phonocardiographic third heart sound and systolic time intervals for the prediction of left ventricular dysfunction.

BACKGROUND: The third heart sound (S3) and systolic time intervals (STIs) are validated clinical indicators of left ventricular (LV) dysfunction. We investigated the test characteristics of a combined score summarizing S3 and STI results for predicting LV dysfunction. METHODS AND RESULTS: A total of 81 adults underwent computerized phonelectrocardiography for S3 and STI (Audicor, Inovise Medical Inc), cardiac catheterization for LV end-diastolic pressure (LVEDP), echocardiography for LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. LV dysfunction was defined as both an LVEDP >15 mm Hg and LVEF <50%. The STI measured was the electromechanical activation time (EMAT) divided by LV systolic time (LVST). Z-scores for the S3 confidence score and EMAT/LVST were summed to generate the LV dysfunction index. The LV dysfunction index had a correlation coefficient of 0.38 for LVEDP (P = .0003), -0.53 for LVEF (P < .0001), and 0.35 for BNP (P = .0008). This index had a receiver operative curve c-statistic of 0.89 for diagnosis of LV dysfunction; a cutoff >1.87 yielded 72% sensitivity, 92% specificity, 9.0 positive likelihood ratio, and 88% accuracy. CONCLUSIONS: In this preliminary study, the LV dysfunction index combined S3 and STI data from noninvasive electrophonocardiography, and yielded superior test characteristics compared to the individual tests for the diagnosis of LV dysfunction.

The physical examination in heart failure--Part I.

The major components and merits of the physical examination of patients with heart failure are presented. A staging of the physical examination practiced by most heart failure specialists is proposed based on the information needed at the time of the encounter. The challenges to our subspecialty regarding this diagnostic tool are the prevention of its extinction during an era of seemingly limitless comprehensive laboratory testing, the promotion of its widespread use, and, over the years, the subjection of its components to the rigors of blinded controlled studies. Part I addresses the staging of the physical examination in heart failure, general observation of the patient, vital signs, and assessment of arterial pulse and neck veins.

The physical examination in heart failure--Part II.

The major components of the physical examination of patients with heart failure are presented to allow practical application by physicians and nurses working in this arena. Part II contains the key elements of the chest, precordial-cardiac, hepatic, and peripheral examination in this specific clinical setting. Supplemental maneuvers are provided. Finally, the overall role and merits of the physical examination in managing the heart failure patient are discussed.

Computerized acoustic cardiographic insights into the pericardial knock in constrictive pericarditis.

BACKGROUND: One of the clinical hallmarks of constrictive pericarditis is the pericardial knock, a high-pitched early diastolic heart sound. Making the clinical diagnosis of constrictive pericarditis is challenging, as is accurate auscultation of the pericardial knock. HYPOTHESIS: We sought to assess the utility of a computerized acoustic cardiographic device in the assessment of the pericardial knock in patients with constrictive pericarditis. METHODS: We report a case series in which computerized acoustic cardiography (Audicor, Inovise Medical Inc., Portland, OR) is performed in patients with constrictive pericarditis. RESULTS: Three patients with constrictive pericarditis underwent computerized acoustic cardiographic recordings at the time of cardiac catheterization. In each case, initial physical examination by the internist and referring cardiologist did not appreciate a pericardial knock. Acoustic cardiography demonstrated a high-pitched early diastolic sound in each case. Time-frequency representation analyses showed the high-frequency components of the pericardial knock sound. Repeat acoustic cardiography demonstrated resolution of the pericardial knock after pericardiectomy in two patients. CONCLUSIONS: Non-invasive computerized acoustic cardiography can demonstrate the high-pitched pericardial knock in patients with constrictive pericarditis. This may aid the bedside assessment of patients with diastolic heart failure, improving the clinician's ability to appreciate the ausculatory findings in constrictive pericarditis.