Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

Inflammation, Obesity and the Metabolic Syndrome. Implications in Hispanics.

We report clinical and molecular mechanisms relating the process of inflammation involved in the progression of obesity and the metabolic syndrome, emphasizing the cardiovascular problems developed in Hispanic populations. Namely, the incidence, component characteristics and complications of obesity and metabolic syndrome in island Puerto Ricans are described and evidence is presented supporting the fact that the metabolic syndrome may be milder in Puerto Rico than in the mainland United States because it is characterized by less aggressive coronary artery disease and a relatively normal lipid profile. Moreover, data supports the fact that increased serum cholesterol levels produce less myocardial infarctions in Puerto Rico than in mainland Hispanics and Caucasians. In addition, the incidence of ventricular tachycardia, a complication caused by remodeling and ischemia of the heart, may be lower in Puerto Rico than in the United States, although the prevalence of the metabolic syndrome is higher in the island. On the other hand, there is evidence of a rising epidemic of obesity and vascular inflammation in Puerto Rico that suggests that cardiovascular morbidity and mortality in the island will continue to increase in the future decades.

Coronary levels of angiotensin-II and endothelin-I in diabetic patients with and without coronary artery disease.

Two groups of patients were studied to find out the levels of angiotensin-II and endothelin-I in the coronary and peripheral circulation. Group A consisted of eight patients with diabetes mellitus type 2 and coronary artery disease; and Group B with diabetes mellitus without coronary artery disease. Significant differences were found between Group A and B in the levels of both peptides peripherally and intracoronary. This shows the importance of these peptides in the origin of coronary artery disease and progression of the disease in diabetics with coronary artery disease.

Celiac trunk and branches dissection due to energy drink consumption and heavy resistance exercise: case report and review of literature.

Higher doses and consumption of energy drinks leads to cardiovascular effects and potential consequences. Principal components found in energy drinks such as caffeine, guarana and taurine has been related to dilatation, aneurysm formation, dissection and ruptures. There is no evidence showing an integration of these components and its effects in endothelium and aortic walls due to higher levels of pressure during exercises. We report a case of a 44 years male with celiac trunk and branches dissection due to long-term consumption of energy drinks and intense exercise routine. Our proposition relates cell and vessel walls alterations including elasticity in endothelial wall due to higher blood pressure, resistance by intense exercise routine and long-term consumption of energy drinks.

Metabolic Changes After Roux-N-Y Bariatric Surgery In Hispanics.

The objective was to describe the metabolic outcomes 12 months after bariatric surgery (Roux-N-Y) in morbidly obese Hispanic patients, and evaluate the correlation between weight loss and the observed changes. Medical records from a hundred-and-two Hispanic obese patients who underwent bariatric surgery were identified at the University of Puerto Rico (UPR) Hospital. The following variables were obtained before and 12 months after surgery: Body Mass Index (BMI), body weight, total cholesterol (TC), triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), and fasting blood sugar (FBS). Ninety-seven percent of patients underwent Roux-N-Y surgery; 79.4% were females and 44% were diabetics. We observed statistically significant reductions (p < 0.05) 12 months after surgery in: BMI -14.3 (± 6.2) kg/m2, weight -86.1 (± 34.4) Ibs, TC -17.9 (± 32.4) mg/dL, triglycerides -28.7(± 40.6) mg/dL, LDL-15.4 (± 30.6) mg/dL, and FBS -11.3 (± 23.5) mg/dL. HDL, instead increased +5.22 (± 12.9) mg/dL (p < 0.0006). Gastric bypass surgery of the Roux-N-Y significantly improves the lipid profile and FBS levels in obese Hispanic patients. The poor correlation factor between weight loss and these variables suggests that other mechanisms, independent from weight loss, are responsible for these changes.

Heart tumors in Puerto Rico de novo atrial fibrillation as clinical presentation in a subgroup of patients.

OBJECTIVE: Primary cardiac tumors are rare neoplasms in humans, of which the most common is the atrial Myxoma. The objective of this study was to find the incidence of these tumors at the Heart Center of Puerto Rico and the Caribbean. METHODS: This study was approved by the Institutional Review Board of the Medical Sciences Campus University of Puerto Rico to review the records at the Heart Center of patients with heart tumors in the last 14 years. RESULTS: The sample consists of 55 patients (78.9% were females and 24.1% were male) with a median age of 52 years. Sixty-five percent of patients lived in rural areas. Clinical presentations included shortness of breath (43.1%), chest pain (37.9%), asymptomatic (25%), palpitations (20.7%), neurologic symptoms (10.3%) and dizziness (6.9%). Electrocardiographic findings included normal sinus rhythm (53.4%), non-specific ST-T changes (32.8%), sinus tachycardia (20.7%), left atrial enlargement (10.3%) and atrial fibrillation (8.6%). A subgroup presenting with atrial fibrillation prior to diagnosis had left atrial myxoma. The tumors found, in descending order of frequency are: left atrial myxoma, right atrial myxoma, papillary fibroelastoma, hamartoma, lipoma and rhabdomyoma. We found a correlation between large left atrial myxoma and atrial fibrillation. CONCLUSION: The most frequent heart tumor was atrial myxoma. The larger myxomas were associated with atrial fibrillation.

Incidence, in-hospital case-fatality rates, and management practices in Puerto Ricans hospitalized with acute myocardial infarction.

OBJECTIVE: There are extremely limited data on minority populations, especially Hispanics, describing the clinical epidemiology of acute coronary disease. The aim of this study is to examine the incidence rate of acute myocardial infarction (AMI), in-hospital case-fatality rate (CFR), and management practices among residents of greater San Juan (Puerto Rico) who were hospitalized with an initial AMI. METHODS: Our trained study staff reviewed and independently validated the medical records of patients who had been hospitalized with possible AMI at any of the twelve hospitals located in greater San Juan during calendar year 2007. RESULTS: The incidence rate (# per 100,000 population) of 1,415 patients hospitalized with AMI increased with advancing age and were significantly higher for older patients for men (198) than they were for women (134). The average age of the study population was 64 years, and women comprised 45% of the study sample. Evidence-based cardiac therapies, e.g., aspirin, beta blockers, ACE inhibitors/angiotensin receptor blockers, and statins, were used with 60% of the hospitalized patients, and women were less likely than men to have received these therapies (59% vs. 65%) or to have undergone interventional cardiac procedures (47% vs. 59%) (p<0.05). The in-hospital CFR increased with advancing age and were higher for women (8.6%) than they were for men (6.0%) (p<0.05). CONCLUSION: Efforts are needed to reduce the magnitude of AMI, enhance the use of evidence-based cardiac therapies, reduce possible gender disparities, and improve the short-term prognoses of Puerto Rican patients hospitalized with an initial AMI.

Magnesium: the forgotten electrolyte.

UNLABELLED: Magnesium (Mg++), Potassium (K+) and Calcium (CA++) are important electrolytes in keeping a stable electrical status. The purpose of this study was to measure them in critically ill patients. METHODS: We evaluated the electrolytes in 28 consecutive patients. Eighteen were females and 10 males with mean age of 62 +/- 5 years. RESULTS: The admission diagnosis in 95% of the cases was congestive heart failure. Sixty-four percent of the patients had subnormal values of Mg++, 53% subnormal values of K+, and 28% subnormal values of CA++. Fourteen percent showed lower values of the three electrolytes and 35% only of Mg++ and K+ concomitantly. Twenty-eight percent showed prolonged QTC interval. All patients with prolonged QTC interval had low Mg++ and K+ levels. Twenty five percent of the patients showed atrial fibrillation, 25% ventricular tachycardia, and 3% junctional tachycardia. The ventricular tachycardia group had more electrolyte abnormalities than those with atrial fibrillation. None of the patients received Mg++ replacement during critical management while 50% received K+ replacement. CONCLUSION: This data shows physician overlook the Importance of Mg++ and K+ deficiency in critically ill patients.

Higher incidence of atrial fibrillation in the metabolic syndrome: a Hispanic population study.

UNLABELLED: The metabolic syndrome is probably one of the main medical problems in developing countries. Purpose of this investigation was to study the metabolic syndrome at the Puerto Rico and Caribbean Cardiovascular Center with emphasis on the cardiovascular complications. MATERIALS/METHODS: The medical charts in the last six years of the metabolic syndrome were evaluated at the PRCCC. RESULTS: One Hundred and Seventy-Three patients met the consensus criteria of the metabolic syndrome. The mean age was 60 years. Fifty-seven percent were males and 42% females. The mean body mass was 30 kg/m. The ejection fraction was subnormal (49 +/- 8%). The end systolic dimension of the left atrium was increased (45 +/- 10mm) when compared to normal. The incidence of atrial fibrillation was 16%. CONCLUSIONS: The metabolic syndrome in this sub-group of Hispanics, showed a higher incidence of atrial fibrillation without ventricular tachycardia. This is probably related to abnormal left ventricular and atrial function.

Basiliximab and heart transplantation in Hispanics: the experience in Puerto Rico.

BACKGROUND: Induction immunotherapy in addition to standard triple therapy at the time of cardiac transplantation with cytolytic antibodies has been used in recipients with pre transplant renal impairment, and to prevent rejection. Recently, anti-interlukin-2 receptor monoclonal antibodies have been used for these purposes. A retrospective study of 58 heart transplant recipients was conducted to assess the effect of basiliximab, a chimeric anti-interlukin-2 receptor monoclonal antibody on biopsy proven acute rejection, serum creatinine, creatinine clearance, hospitalizations due to infection and mortality one year after transplantation. METHODS: A total of 58 heart transplant patient's charts were reviewed. All patients received triple immunosuppressive therapy with cyclosporine or tacrolimus, mycophenolate mofetil and prednisone post transplant. Basiliximab 20 mg on day 0 and day 4 was administered as induction therapy in a subgroup of patients. Both groups had similar pre transplant characteristics. Analysis was performed at intervals of 0-17 weeks, 18-34 weeks, 35-52 weeks, and one year overall. The incidence of acute rejection episodes, post-transplant renal function, patient survival and hospitalizations due to infection was analyzed. RESULTS: Twenty-seven patients received induction therapy with basiliximab and 31 patients did not. Basiliximab induction helped reduce acute rejection overall during the first year, with 22 episodes of rejection in the induction group, and 67 episodes in the no induction group. In the 0-17 weeks following transplantation there were 20 reported rejection episodes in the induction group versus 58 rejection episodes in the no-induction group, demonstrating also reduction of rejection by induction in this group. Basiliximab induction group had preserved renal function, with higher creatinine clearance at 1 year when compared to the no induction group. There were no differences between groups in terms of hospitalizations due to infections or mortality. CONCLUSION: Induction therapy with basiliximab significantly reduced the number of acute rejection within the first year after heart transplantation, without a negative impact on patient's renal function, risk of infection or mortality.

Heart transplantation in females: the experience in Puerto Rico.

BACKGROUND: Heart transplantation is the procedure of choice for a selected group of patients with end stage heart disease. Gender related differences have been observed in the heart transplant field: less women than men are recipients of heart transplants, more risk of rejection in female recipients, and a perception toward reduced survival in women. We report our experience of heart transplantation in females in Puerto Rico. METHODS: We studied the data bank of 69 heart transplant recipients in the Puerto Rico Heart Transplant Program from June 1999 to June 2005. Gender related differences in the number of recipients: males or females, incidence of rejection, survival, and other outcomes were analyzed. RESULTS: 69 patients received an orthotopic heart transplant from June 1999 to June 2005, in a single center in Puerto Rico. The mean age of the patients was 47 (11-62) years. Fifty patients (72%) were men, and 19 patients (28%), were women. Survival in the female group at 3 months, 1, 2, 3, 4, and 5 years was 100%, 100%, 100%, 100%, 90%, and 90% respectively. The survival in the male group at 3 months, 1, 2, 3, 4 and 5 years was 97%, 97%, 97%, 94%, 86 and 79% respectively. There was an early, higher incidence of rejection in women during the first three months post transplant; 1.5 vs. 0.75, (P=0.04) episodes per patient in the female, and male group respectively. After the third month post transplant there was no significant difference in rejection incidence. The incidence of infectious episodes was significantly more frequent in female than in male recipients, 2.8 vs. 1 (P=0.02) per patient respectively. CONCLUSIONS: There were more male than female heart transplant recipients at a ratio of 3:1, without a significant gender difference in survival. The risk of rejection was higher in females in the early period post transplantation, but thereafter this risk showed no signinificant statistical difference. The incidence of infection was more frequent in female than in male recipients.

Effects of Enalaprilat on Regional Wall Stress in Patients with Angina Pectoris.

Left ventricle (LV) cineventriculograms silhouettes in the right anterior oblique projection with simultaneous pressure micromanometry were assessed before and 10 min after administration of 1.25 mg enalaprilat intravenously to 10 patients with angina pectoris undergoing diagnostic cardiac catheterization. Cineventriculograms were divided into 20 areas using a modified Leighton's method for segmentalization of the LV and computed by the Janz's method for regional wall stress. Enalaprilat reduced preload and afterload in all cases. There was significant reduction in regional wall stress in 15 of the 20 segments after enalaprilat administration compared with baseline analysis. Segments without significant reduction in wall stress wee apical. There was significant reduction in global wall stress after enalaprilat. Thus, enalaprilat, in addition to improve hemodynamics decreasing both preload and afterload, reduces LV wall stress both regional and global. Clinical implications of these findings are in agreement with the wall stress reduction for prevention of ventricular remodeling with this agent in postinfarction patients.

Transient elevation of pulmonary arterial pressure induced by sublingual angiotensin converting enzyme inhibitors

Twelve patients with ischemic heart disease had complete left and right catheterization before and after sublingual captopril. Hemodynamic measurements were ten (10) minutes apart and were monitored for thirty (30) minutes. The heart rate increased from 70 +/- 13 to 76 +/- 11 beats/minute (P = .04). There was no change in the arterial blood pressure, although the systemic vascular resistance decreased from 1500 +/- 400 to 1026 +/- 480 dynes-sec-cm-5 (P < .0001). The pulmonary artery pressure was increased 15 +/- 6 to 25 +/- 5mmHg (P = .005) and the pulmonary vascular resistance increased from 288 + 160 to 376 + 160 dynes-sec-cm-5 (P < .0001). The wedge pressure increased from 7 +/- 2 to 14 +/- 3 mmHg (P = .05). The cardiac output (CO) increased from 5.06 +/- 1.06 to 578 +/- 1.58 Lt/min. (P.05 =. The left ventricular end diastolic volume (LVEDV) increased from 128 +/- 40 to 145 +/- 37cc)P = .002), without change in the end systolic volume (ESV). The ejection fraction (EF) increased from 56 +/- 3 to 61 +/- 4 per cent (P = .02). These pressure changes appeared at two (2) minutes and disappeared after thirty (30) minutes. The study shows that, sublingual captopril produces a transient elevation of the pulmonary artery pressure and resistance

The use of biosensors in pacemaker technology: experience with a ventricular rate responsive pacemaker

Ten elderly patientes each had a ventricular rate responsive pulse generator (Activitrax) placed in then to help correct severe conduction abnormalities; none had suspected ischemic heart disease. The pulse generator was programmed to a maximal pacing rate of 125 ppm, a medium activity threshold, and a rate response of 6. Six weeks after implantation of the pulse generator, the patients were evaluated before exercing and again when the pacing rate reached 125ppm. The evaluation protocol included an M-mode echocardiogram from which the following measurements were taken; the left ventricular end-diastolic volume (EDV), the end-systolic volume (ESV), the ejection fraction (EF), and the peak systolic pressure/end-systolic volume (PSP/ESV). The numerical values were recorded, clculated, and compared statically with the following results: the EDV increased from 91 ñ 10 to 125 ñ 20 cc (p < .05); the ESV decreased from 64 ñ 10 to 24 ñ 6cc (p < ..005); the EF increased from 41 ñ 5 to 61 ñ 10% (p < .05); and the PSP/ESV ratio increased from 1.70 ñ 1 to 4.10 ñ 2mm Hg/cc (p = 10). Also, during the maximal pacing rate, the septum of all patients showed paradoxical septal motion. All patients in our study have been asymptomatic and have shown an increase in their exercise capacity. We conclude that during exercise the left ventricular function ins influenced more by heart rate than by AV synchrony, as indicated by an elevated EDV in most patients

Left, ventricular function in adults with atrial septal defect

Dieciseis pacientes con un defecto interatrial fueron cateterizados enfatizando el análisis cuantitativo del ventrículo al final de sístole y a mitad de expulsión. La fracción de expulsión promedio estuvo reducida 57 + 8% cuando fue comparada con un grupo control (71 + 10%) P < .005. Ocho pacientes tuvieron volumenes diastólicos elevados (156 + 10cc) al compararles con el grupo control (95 + 100cc) P <.005. Un total de 32 áreas hipoquinéticas y 35 tardoquinéticas se encontraron. Ocho pacietnes fueron reestudiados después de nitroglicerina sublingual (4mg). Se encontró un aumento en la fracción de expulsión de 54% a 70% (P <.005). La mayoria de las áreas hipoquinéticas fueron normalizadas. No se encontró una correlación entre la fracción de expulsión o movimiento sistólico total y el tamaño del corto circuito. Probablemente estas anormalidades son primarias y no debidas al cortocircuito intracardíaco