Call to action: cardiologists should promote influenza vaccination.

The COVID-19 pandemic has spurred clinical and scientific interest in the cardiology community because of the significantly enhanced vulnerability of patients with underlying cardiac diseases. COVID-19 vaccination is therefore of vital importance to the patients we see in our clinics and hospitals every day and should be promoted by the medical community, especially cardiologists. In view of vaccine-preventable diseases, the association between influenza and cardiovascular complications has been widely investigated. Several studies have found a substantially elevated risk of hospital admission for acute myocardial infarction in the first 7 days after laboratory-confirmed influenza, with incidence ratios ranging from 6.05-8.89. The effectiveness of the influenza vaccine to protect against acute myocardial infarction is about 29%. This effectiveness is comparable to or even better than that of existing secondary preventive therapies, such as statins (prevention rate approximately 36%), antihypertensives (prevention rate approximately 15-18%), and smoking cessation (prevention rate approximately 26%). As the influenza season is rapidly approaching, this Point of View article serves as a call to action: Cardiologists should promote influenza vaccination and actively advice their patients to get the seasonal influenza vaccination.

Circulating annexin A5 predicts mortality in patients with heart failure.

BACKGROUND: Natriuretic peptides are currently used to predict mortality in patients with heart failure (HF). However, novel independent biomarkers are needed to improve risk stratification in these patients. We hypothesized that annexin A5 (anxA5) would be highly expressed by organs which are generally affected by HF and that circulating anxA5 levels would predict mortality in HF patients. METHODS: We prospectively determined the diagnostic value of anxA5, N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and estimated glomerular filtration rate (eGFR) to predict mortality in 180 HF patients during a median follow-up of 3.6 years. Studies were conducted with anxA5(-/-) mice to investigate the underlying mechanisms. RESULTS: AnxA5 levels were significantly elevated in HF patients compared to healthy control subjects. Cox regression analysis demonstrated that anxA5, NT-proBNP and eGFR all predict mortality independently. AnxA5 significantly improved the diagnostic efficiency of NT-proBNP alone (improvement of c-statistic from 0.662 to 0.705, P < 0.001) and also combined with eGFR and CRP (improvement of c-statistic from 0.675 to 0.738, P < 0.001) to predict mortality in the Cox regression model. Receiver operating characteristic curve analysis showed that anxA5 predicted 3-year survival (area under curve 0.708) with an optimal cut-off value of 2.24 ng mL(-1) . Using anxA5(-/-) mice, we demonstrated that anxA5 is highly expressed in organs that are often affected by HF including lung, kidney, liver and spleen. Lysis of these organs in vitro resulted in a marked and significant increase in anxA5 concentrations. CONCLUSION: AnxA5 improves the diagnostic efficiency of conventional biomarkers to predict mortality in HF patients. Whereas natriuretic peptides originate from the myocardium, high circulating anxA5 levels in patients with HF are likely to reflect peripheral organ damage secondary to HF.

The importance of cultural tailoring of communicators and media outlets in an influenza vaccination awareness campaign: a digital randomized trial.

The COVID-19 pandemic has exposed the vulnerability of ethnic minorities again. Health inequity within ethnic minorities has been explained by factors such as higher prevalence of underlying disease, restricted access to care, and lower vaccination rates. In this study, we investigated the effect of cultural tailoring of communicators and media outlets, respectively, on vaccine willingness in an influenza vaccination campaign in the Netherlands. A total of 1226 participants were recruited from two culturally non-tailored media outlets (Dutch newspaper and Facebook), and one media outlet tailored to a large community in the Netherlands with Indian ancestry. The participants from all three media outlets were randomly exposed to a vaccination awareness video delivered by a physician with an Indian or Dutch background, followed by an online survey. Cultural tailoring compared to cultural non-tailoring of communicators showed no difference in improvement of vaccine willingness (13.9% vs. 20.7% increment, respectively, p = 0.083). However, the media outlet tailored to the community with Indian ancestry, resulted in a higher improvement of vaccine willingness compared to non-tailored media outlets (46.7% vs. 14.7% increment, respectively, p < 0.001, unadjusted OR = 5.096). These results suggest that cultural tailoring of media outlets may be critical to effectively reach out to ethnic minorities to help optimize vaccination rates and improve general health.

Plug and seal: prevention of hypoxic cardiocyte death by sealing membrane lesions with antimyosin-liposomes.

The hallmark of cell death is the development of cell membrane lesions. Such lesions in the myocardium are usually associated with acute myocardial infarction. Minimizing myocardial necrosis by thrombolytic reperfusion therapy constitutes the only major treatment to date. We envisioned a method to seal these membrane lesions using immunoliposomes as a novel adjunctive approach. An antigen to intracellular cytoskeletal myosin in hypoxic embryonic cardiocytes is used as an anchoring site, and a specific antibody on immunoliposomes as the anchor to plug and to seal the membrane lesions. H9C2 cells were used because they are cardiocytes and are propagated in tissue culture and their viability may be assessed by various methods. Viability assessed by [3H]thymidine uptake in hypoxic cardiocyte cultures (n = 6 each) treated with antimyosin-immunoliposomes (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to that of normoxic cells (3.68 +/- 0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells (0.115 +/- 0.155 x 10(6) c.p.m.) or hypoxic cells treated with plain liposomes (1.140 +/- 0.577 x 10(6) c.p.m.). These results were reconfirmed by trypan blue exclusion and by fluorescent, confocal and transmission electron microscopy. They indicated that cell death in hypoxic cardiocytes can be prevented by targeted cell membrane sealing. This concept of cell salvage should be applicable in the prevention of cell death in different biological systems.

Annexin-V imaging for noninvasive detection of cardiac allograft rejection.

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody.

CD44 is a M(r) 90,000 surface glycoprotein believed to be involved in cell adhesion and migration. We investigated the role of CD44 in tumor growth and metastasis using human melanoma cell lines SMMU-1 and SMMU-2. Both SMMU-1 and SMMU-2 form tumors in the s.c. tissues when injected s.c. in SCID mice but only SMMU-2 metastasizes. Approximately one-half of SCID mice receiving injections of SMMU-2 s.c. develop metastatic tumors. SMMU-2 but not SMMU-1 expresses high levels of the hematopoietic form of CD44 and binds fluorescence-conjugated hyaluronic acid in vitro. GKW.A2 is a monoclonal antibody specific for human CD44 that can completely inhibit the binding of hyaluronic acid to SMMU-2 tumor cells in vitro. Moreover, in vivo injection of GKW.A3 inhibited the growth and metastatic potential of SMMU-2 tumor cells. Administration of GKW.A3 i.v. 1 week after s.c. tumor injection did not inhibit local tumor development but inhibited the formation of metastatic tumors and prolonged animal survival. Therefore, interactions between CD44 on tumor cells and its ligands in vivo may be necessary for tumor growth and metastasis.

Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium.

Biodistribution and infarct accumulation of different liposome preparations in rabbits with experimental myocardial infarction have been investigated. The influence of such parameters as liposome size, and presence or absence of poly(ethylene glycol) (PEG) and infarct-specific antimyosin antibody (AM) on liposome behavior in vivo was studied. All three variables were shown to affect liposome biodistribution, liposome size being the least significant variable. Statistical analysis of the data obtained demonstrated that of all variables, PEG coating expresses the strongest influence on the liposome blood clearance, significantly (P=0.0001) increasing the mean level of blood radioactivity under all circumstances. Infarct accumulation depended upon the presence of both PEG (P=0.0013) and AM (P=0.005). The infarct-to-normal ratio was affected by the presence of AM (P=0.0002), but the extent of the effect depended also on the presence of PEG (P=0.01). Two differing mechanisms can be seen in infarct accumulation of PEG-liposomes (slow accumulation via the impaired filtration) and AM-liposomes (specific binding of immunoliposomes with the exposed antigen). Both mechanisms are supplementary in case of liposomes carrying PEG and AM at the same time. An optimization strategy is suggested for using liposomes as carriers for diagnostic (a high target-to-nontarget ratio is required) and therapeutic (a high absolute accumulation in the target is required) agents.

Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet.

BACKGROUND: Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function. METHODS AND RESULTS: We examined the effects of cholesterol feeding (0.5%) on cardiac function in rabbits. After 10 weeks, both systolic shortening and diastolic relaxation rates were impaired without any change in aortic pressure or ventricular hypertrophy. However, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2 mRNA levels were reduced within 4 days after initiation of cholesterol feeding. After this effect, SERCA-2 protein and SERCA-mediated Ca uptake into sarcoplasmic reticulum vesicles were impaired, and the ratio of MHC-beta to MHC-alpha mRNA increased 5-fold. Suppression of the SERCA-2 message correlated temporally with enrichment of the cardiac sarcolemma with cholesterol. CONCLUSIONS: These data demonstrate that dietary hypercholesterolemia induces a "cholesterol cardiomyopathy" characterized by systolic and diastolic dysfunction. These alterations were independent of vascular disease and demonstrate a dietary link to cardiac dysfunction.

Laser catheter-induced atrioventricular nodal delays and atrioventricular block in dogs: acute and chronic observations.

Selective modification of atrioventricular (AV) nodal conduction, that is, induction of varying degrees of AV nodal delays or block (second or third degree), or both, was achieved with a pervenous laser catheter technique. In six adult mongrel dogs anesthetized with pentobarbital (Nembutal), 5F leads were placed through femoral and external jugular veins and placed into the right atrium and His bundle region. Through another femoral vein, a 200 micron optical fiber was inserted by way of a 7F catheter with a preformed curved tip. Guided by fluoroscopy and His bundle electrograms, the fiber's tip was positioned in the AV nodal region. After autonomic blockade was achieved with intravenous propranolol (5 mg) and atropine (1 mg), AV conduction was analyzed. An argon laser delivered 3 to 4 watts into the fiber in bursts of 10 seconds' duration until the desired degree of AV nodal delay or block (second or third degree) was manifested. Monitoring of His bundle electrograms was continued for 2 hours. Four weekly serial electrocardiograms were recorded, after which electrophysiologic studies were repeated. Acute post-lasing studies showed that: in all six dogs, the mean PR interval was prolonged from 116 ms (range 100 to 135) to 153 ms (range 120 to 185), with the prolongation being caused exclusively by AH lengthening from 68 ms (range 50 to 90) to 105 ms (range 65 to 140); the mean effective refractory period of the AV node increased from less than 185 ms (range less than 150 to less than 200) to 215 ms (range 190 to 280); and the mean atrial pacing cycle length, at which second degree AV nodal block was manifested, increased from 210 ms (range 160 to 260) to 261 ms (range 205 to 320).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of biopsy classification for rejection: relation to detection of myocardial damage by monoclonal antimyosin antibody imaging.

OBJECTIVES: This study sought to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global estimate of myocardial transplant-related cardiac damage detected by myocardial uptake of monoclonal antimyosin antibodies. BACKGROUND: The diagnosis and treatment of acute cardiac allograft rejection is based on the interpretation of endomyocardial biopsies. Because allograft rejection is a multifocal process and biopsy is obtained from a small area of the right ventricle, sampling error may occur. Global assessment of myocardial damage associated with graft rejection is now possible with the use of antimyosin scintigraphy. The present study was undertaken to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global assessment of transplant-related myocardial damage detected by antimyosin scintigraphy. METHODS: Biopsies (n=395) from 112 patients were independently interpreted by three pathologists in a blinded manner according to the original Stanford four-grade (normal, mild, moderate and severe) and the current International Society of Heart and Lung Transplantation (ISHLT) seven-grade (0, 1A, 1B, 2, 3A, 3B and 4) classifications. The results were correlated with 395 antimyosin studies performed at the time of the biopsies. The heart/lung ratio of antimyosin antibody uptake was used to assess the severity of myocardial damage. RESULTS: In the Stanford biopsy grade classification, significantly higher antimyosin uptake, indicating increasing degrees of myocardial damage, were associated with normal (1.78+/-0.26), mild (1.88+/-0.31) and moderate (1.95+/-0.38) biopsy classifications for rejection (p < 0.01). In the ISHLT classification, significant differences were detected only for antimyosin uptake associated with grades 0 (1.77+/-0.26) and 3A (1.98+/-0.39) but not for intermediate scores (1A, 1B and 2). In view of the similar intensity of antibody uptake among the various grades, ISHLT biopsy scores were regrouped: normal biopsies in grade A; 1A and 1B as grade B; and 2 and 3A as grade C. Antimyosin uptake in grades A, B and C was 1.78+/-0.26, 1.88+/-0.31, 1.95+/-0.38, respectively (p < 0.01). CONCLUSIONS: The current ISHLT seven-grade scoring system does not reflect the progressive severity of myocardial damage associated with heart transplant rejection. Because myocardial damage constitutes the basis of treatment for allograft rejection, there is a need to reevaluate the ISHLT grading system, given its importance for multicenter trials.

Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy.

OBJECTIVES: To assess the prevalence of dystrophin defects in dilated cardiomyopathy (DCM) in male patients and to formulate investigation strategies for their identification. BACKGROUND: Dystrophin defects presenting with predominant or exclusive cardiac involvement may be clinically indistinguishable from "idiopathic" DCM. Diagnosis may be missed, unless specifically investigated. METHODS: Clinical and biochemical evaluation, right ventricular endomyocardial biopsy (EMB), light and electron microscopic and immunohistochemical studies of biopsy samples, six multiplex and two single polymerase chain reactions for 38 exons and automated sequencing of exon 9 and muscle promoter-exon 1 were undertaken in 201 consecutive male patients presenting with DCM, with (n = 14) and without (n = 187) increased serum creatine phosphokinase (sCPK). RESULTS: Dystrophin defects were identified in 13 of the 201 patients (6.5%, age 16-50). Family history was positive in four patients. Serum CPK levels were increased in 11 of 13 patients. Light microscopy examination of EMB was uninformative; ultrastructural study showed multiple membrane defects. Dystrophin immunostain was abnormal. Eight patients, all older than 20, had deletions affecting midrod domain, normal or mildly increased CPK and better outcome than the five remaining cases all younger than 20, with more than five-fold increase of sCPK. Two of these latter had proximal and rod-domain deletions. Sisters of two patients were diagnosed as noncarriers with microsatellite analysis. CONCLUSIONS: Although the overall prevalence of dystrophin defects in our consecutive DCM male series is low (6.5%), immunohistochemical and molecular studies are essential to identify protein and gene defects; screening studies are justified to define prevalence, clinical profile and genotype-phenotype correlation.

Myocardial cell damage in human hypertension.

OBJECTIVES: The goal of this study was to investigate the presence of myocardial cell damage in patients with systemic hypertension and its relationship with left ventricular hypertrophy (LVH). BACKGROUND: Although initially compensatory, LVH adversely affects myocellular integrity and contributes to congestive heart failure in hypertensive patients. Noninvasive detection of myocardial damage can be of value. METHODS: We performed imaging studies with 111In-labeled monoclonal antimyosin antibodies to identify myocardial damage in 39 patients with systemic hypertension and variable degrees of LVH. Three groups were considered: 16 asymptomatic patients with normal echocardiographic left ventricular mass (LVM) (group I); 14 asymptomatic patients with LVH (group II) and 9 patients with symptomatic hypertensive heart disease and advanced LVH (group III). The severity of myocardial damage was represented as heart-to-lung (target-to-background) antibody uptake ratio (normal: <1.55). RESULTS: Mean LVM index was 105+/-14 g/m2 in group I, 124+/-24 in group II and 174+/-29 in group III. Heart-to-lung ratios of antimyosin uptake were: 1.45+/-0.14 in group I, 4 of the 16 (25%) patients showing an abnormal scan; 1.50+/-0.07 in group II with abnormal scans in 2 of the 14 (16%) patients and 1.77+/-0.16 (p < 0.001) in group III, all 9 patients presenting with abnormal antimyosin scans. On multivariate regression analysis LVM index was the main variable that independently correlated with the degree of myocardial uptake of antimyosin (r = 0.815; p = 0.001). CONCLUSIONS: This study provides the first in vivo evidence of myocyte damage in patients with hypertension. The severity of myocardial damage can be related to the magnitude of LVH.

Noninvasive characterization of stunned, hibernating, remodeled and nonviable myocardium in ischemic cardiomyopathy.

OBJECTIVES: We evaluated a novel protocol of dual-isotope, gated single-photon emission computed tomographic (SPECT) imaging combined with low and high dose dobutamine as a single test for the characterization of various types of altered myocardial dysfunction. BACKGROUND: Myocardial perfusion tomography and echocardiography have been used separately for the assessment of myocardial viability. However, it is possible to assess perfusion, function and contractile reserve using gated SPECT imaging. METHODS: We studied 54 patients with ischemic cardiomyopathy using rest and 4 h redistribution thallium-201 imaging and dobutamine technetium-99m sestamibi SPECT imaging. The sestamibi images were acquired 1 h after infusion of the maximal tolerated dose of dobutamine and again during infusion of dobutamine at a low dose to estimate contractile reserve. Myocardial segments were defined as hibernating, stunned, remodeled or scarred. RESULTS: Severe regional dysfunction was present in 584 (54%) of 1,080 segments. Based on the combination of function and perfusion characteristics in these 584 segments, 24% (n = 140) were labeled as hibernating; 23% (n = 136) as stunned; 30% (n = 177) as remodeled; and 22% (n = 131) as scarred. Contractile reserve, represented by improvement in wall motion/thickening by low dose dobutamine, was observed in 83% of stunned, 59% of hibernating, 35% of remodeled and 13% of scarred myocardial segments (p<0.05). CONCLUSIONS: It is possible with this new imaging technique to characterize dysfunctional myocardium as stunned, hibernating, remodeled and nonviable. These subtypes often coexist in the same patient.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation.

OBJECTIVES: The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND: Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS: In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS: Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS: The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Antimyosin scintigraphy in cardiovascular diseases.

Antimyosin antibody is highly specific for in vivo delineation of acute myocyte necrosis as only irreversibly damaged myocytes with sarcolemmal disruption will enable access of the administered antibody to the once-privileged intracellular antigen-myosin. Thus, antimyosin radiolabeled with either indium-111 or technitium-99m has been used for the noninvasive diagnosis of myocyte necrosis associated with acute myocardial infarction, myocarditis, heart transplant rejection, as well as in other cardiac disorders such as rheumatic carditis or adriamycin cardiotoxicity. The sensitivity of antimyosin scintigraphy for these disorders has been reported to be 90%-100%. The final verdict on its full potential must await extensive clinical use.

Radionuclide imaging of the synthetic smooth muscle cell phenotype in experimental atherosclerotic lesions.

Although the exact mechanisms of atherogenesis have not yet been elaborated, it is believed to be an inflammatory immunological response of the injured intima. The molecules and cells involved in this inflammatory response may provide specific targets for the development of novel diagnostic modalities. The present review deals with use of antibodies specific for the neoantigens of the vascular smooth muscle cells of the transformed synthetic phenotype for the detection of atherosclerotic lesions, as well as the potential use of the upregulation of the purinoceptors as indicators of the phenotypic transformation of these cells. In addition to the recognition of atherosclerotic lesions, such a strategy may also help identify accelerated proliferating smooth muscle cells associated with postangioplastic restenosis. © 1996, Elsevier Science Inc. (Trends Cardiovasc Med 1996;6:226-232).

Outcomes in recipients of combined heart-kidney transplantation: multiorgan, same-donor transplant study of the International Society of Heart and Lung Transplantation/United Network for Organ Sharing Scientific Registry.

In patients awaiting heart transplantation, end-stage disease of a second organ may occasionally require consideration of simultaneous multiorgan transplantation. Outcome statistics in multiorgan transplant recipients are needed to define optimal utilization of scarce donor resources. Incidence of cardiac allograft rejection, actuarial recipient survival, and cardiac allograft rejection-free survival were evaluated in 82 recipients of 84 simultaneous heart and kidney transplants. Twenty-three of the 82 dual-organ recipients have died with 1, 6, 12, and 24-month actuarial survival rates of 92%, 79%, 76%, and 67%, respectively. The actuarial survival rates in the heart-kidney recipients were similar to those observed in 14,340 isolated heart recipients (United Network for Organ Sharing Scientific Registry) during the same period (92%, 86%, 83%, and 79%, respectively; P=0.20). Clinical data on all episodes of treated rejection in either organ and on immunosuppressive regimens were available on 56 patients; 48% of these patients have had no rejection in either organ, 27% experienced heart rejection alone, 14% experienced kidney rejection alone, and 11% had both heart and kidney allograft rejection. Heart allograft rejection was less common in heart-kidney recipients, as compared with isolated heart transplant recipients; 0, 1, and > or = 2 treated cardiac allograft rejection episodes occurred in 63%, 20%, and 18% of heart-kidney recipients compared with 46%, 27%, and 28% of 911 isolated heart recipients reported by Transplant Cardiologists' Research Database (P=0.02). The rejection-free survival rates at 1, 3, and 6 months were 88%, 74%, and 71% in the double-organ recipients, as compared with 66%, 44%, and 39%, respectively, in the single-organ recipients. Compared with isolated heart transplantation, combined heart-kidney transplantation does not adversely affect intermediate survival and results in a lower incidence of treated cardiac allograft rejection. The findings suggest that combined heart-kidney transplantation may be an acceptable option in a small subset of potential heart transplant recipients with severe renal dysfunction.

Sympathetic reinnervation of cardiac allografts evaluated by 123I-MIBG imaging.

UNLABELLED: Some heart-transplant patients present with improved heart rate response to exercise and anginal pain suggesting reinnervation of allografts. Studies performed up to 5 y post-transplantation have suggested that reinnervation is a slow process that occurs only after 1 y post-transplantation. The purpose of this study was to evaluate the extent of sympathetic reinnervation in heart-transplant patients and its relation to cardiac function. METHODS: We performed 123I-metaiodobenzylguanidine (MIBG) studies and rest/exercise radionuclide ventriculography in 31 heart-transplant patients 6 mo to 12 y post-transplantation. Intensity of myocardial MIBG uptake was quantified by a heart-to-mediastinum ratio (HMR), and the regional distribution of MIBG was determined by tomographic studies. RESULTS: HMR correlated positively with time after transplantation (r = 0.607, P < 0.001). Patients studied from 2 to 12 y post-transplantation had an HMR significantly higher than patients studied before 2 y post-transplantation (1.62 +/- 0.2 versus 1.34 +/- 0.2, P < 0.05). Myocardial MIBG uptake was anterolateral in 16 patients, anterior in 3 and anterolateral and septal in 3. Myocardial MIBG uptake was absent in 9 patients. Vasculopathy developed in 8 patients, and 5 of them (63%) had decreased myocardial MIBG uptake. Peak filling rate was higher in patients studied from 2 to 12 y post-transplantation (2.7 +/- 0.8 end-diastolic volume (EDV)/s versus 2.16 +/- 0.5 EDV/s, P = 0.02). CONCLUSION: Sympathetic reinnervation increases with time after heart transplantation and is seen more frequently after 2 y post-transplantation. Complete reinnervation of the transplanted heart does not occur even up to 12 y post-transplantation. Early vasculopathy may delay the process of sympathetic reinnervation.

Evaluation of myocardial infarct size before and after reperfusion: dual-tracer imaging with radiolabeled antimyosin antibody.

UNLABELLED: Antimyosin antibody is a specific marker of myocardial necrosis that is based on the loss of integrity of the sarcolemmal membrane. Because antimyosin can be labeled with several different radiotracers, gamma imaging performed with antimyosin labeled with two different radionuclides can be used to quantify infarct size before and after an intervention such as reperfusion. METHODS: Twelve open-chested anesthetized dogs were evaluated both at the end of 1.5 hr of occlusion of the left anterior descending coronary artery and following reperfusion. Antimyosin Fab radiolabeled with either 123I or 111In was injected by intracoronary administration over 3 min at the end of the occlusion interval, and the coronary sinus was drained continuously for 7 min to prevent recirculation of the antibody. One hour after reperfusion, a second injection of antimyosin Fab (labeled with a different isotope from the first) was administered as before. Six dogs were given intracoronary trifluoperazine (150 micrograms/kg of body weight) simultaneously with reperfusion, and another six dogs received saline as the control. The infarct size in grams before and after reperfusion was assessed by antimyosin antibody uptake in ex vivo images of 1-cm thick slices of the hearts. The mean infarct sizes before (W1) and after (W2) reperfusion were then calculated as the percent of infarcted myocardium/ventricular myocardial mass. RESULTS: There was a significant increase in the mean percent infarct size after reperfusion in the control group (W2 = 16.73 +/- 4.0, W1 = 14.92 +/- 3.88; p = 0.029). The mean infarct size was uniformly smaller with trifluoperazine intervention (W2 = 12.33 +/- 2.03, W1 = 16.34 +/- 2.78; p = 0.004). The difference between the mean change in the infarct sizes in the two groups was highly significant (p = 0.002). CONCLUSION: Dual imaging of the extent of myocardial necrosis before and after an intervention (reperfusion) in the same animal demonstrated the utility of antimyosin imaging to document changes in the extent of necrosis.

Predictors of outcome of medically treated patients with left main/three-vessel coronary artery disease by coronary angiography.

This study examined the prognostic value of single-photon emission computed tomography in angiographically high-risk patients with left main and/or 3-vessel coronary artery disease who were treated medically. Multivariable Cox survival analysis revealed the single-photon emission computed tomography score (based on size of perfusion abnormality, multivessel abnormality, left ventricular dilation, and lung uptake) as the only independent predictor of outcome.