Biomedical subjects

Krishnan Ramanathan

Publications and source records attributed to Krishnan Ramanathan.

10 recordsLinked to original sources

PubMed2007

Redefining the normal angiogram using population-derived ranges for coronary size and shape: validation using intravascular ultrasound and applications in diverse patient cohorts.

OBJECTIVES: To develop a method for quantitating coronary angiographic abnormalities of segmental size and shape (tapering) in comparison to gender- and segment-specific, population derived, normal values. BACKGROUND: In the absence of obvious focal stenoses, remodeling renders the angiogram insensitive to the presence of atherosclerosis and invalidates use of a "normal reference segment" for calculation of percent diameter stenosis. METHODS: Equations were created for detection of size/shape abnormalities of coronary angiographic segments. After validation using intravascular ultrasound (IVUS), the equations were applied to a cohort of segments judged to be completely normal by a panel of highly experienced, core laboratory technicians; and a cohort of patients judged by an experienced interventionalist to have completely normal coronaries. RESULTS: In patients assessed by core technicians, 53% (162/303) of males, 39% (209/538) of normal segments in males, 60% (56/94) of females, and 40% (81/205) of normal segments in females had quantifiable abnormalities. In patients with normal coronaries as judged by an experienced interventionalist, 100% of males (n = 14) and females (n = 19), 37% (67/182) of segments in males and 43% (105/247) of segments in females had abnormalities. The left main segment was most commonly abnormal. CONCLUSIONS: We propose a set of equations validated using IVUS and based on gender- and segment-specific normal values for coronary angiographic size and shape that markedly improves the sensitivity of the coronary angiogram for detection of abnormalities. The method should replace the unfounded practice of labeling coronary angiograms as "normal" based solely on the failure to detect focal stenoses.

Cohort Studies↗

PubMed2006

Emergency revascularization in patients with cardiogenic shock on admission: a report from the SHOCK trial and registry.

AIMS: To determine clinical correlates and optimal treatment strategy in patients with cardiogenic shock (CS) on admission. METHODS AND RESULTS: In SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) trial and registry patients with left ventricular (LV) dysfunction (n=1053), CS on admission occurred in 26% of directly admitted patients (n=166/627). Time from myocardial infarction to CS was shorter, initial haemodynamic profile poorer, and aggressive treatment less frequent in CS on admission than in delayed CS patients. CS on admission patients constituted a smaller relative proportion (11%) of the transferred (n=48/426) when compared with the directly admitted cohort (P<0.001). In-hospital mortality was higher (75 vs. 56%; P<0.001) with more rapid death (24-h mortality 40 vs. 17%; P<0.001) in CS on admission than in delayed CS patients. Emergency revascularization reduced in-hospital mortality in CS on admission (60 vs. 82%; P=0.001) and in delayed CS patients similarly (46 vs. 62%; P<0.001; interaction P=0.25). After adjustment for clinical differences, CS on admission was an independent predictor of in-hospital mortality (P=0.008). CONCLUSION: CS on admission patients have a worse outcome but benefit equally from emergency revascularization as delayed CS patients, emphasizing the need for rapid and direct access of CS on admission patients to facilities providing this care.

Aged↗

PubMed2006

An early revascularization strategy is associated with a survival benefit for diabetic patients in cardiogenic shock after acute myocardial infarction.

BACKGROUND: The role of diabetes mellitus (DM) in cardiogenic shock (CS) complicating an acute myocardial infarction (AMI) is not well understood. Previous studies have reported an in-hospital mortality rate for patients with DM and CS of about 60%. OBJECTIVES: This study compares the 1-year mortality rates of patients with DM and those without (NDM) and evaluates early revascularization (ERV) compared with initial medical stabilization (IMS) in patients with DM and CS. METHODS: Baseline characteristics, clinical and hemodynamic measures, and management were compared for 90 patients (31%) with DM and 198 with NDM (69%) who were randomized to ERV or IMS in the SHOCK Trial. RESULTS: When compared with NDM, patients with DM were of similar age but had higher rates of prior MI (44.4 vs. 27.8%, p = 0.007) and hypertension (56.2 vs. 42.5%, p = 0.04). The DM group had a lower rate of fibrinolytic therapy (44.4 vs. 60.1%, p = 0.02). In patients randomized to ERV, patients with DM had a higher rate of coronary artery bypass grafting (CABG) (50.0 vs. 30.9%, p = 0.03) despite similar rates of triple-vessel disease. The 1-year mortality rates in both groups were equivalent (58.9%). One-year mortality was not associated with diabetes (hazard ratio [HR] 1.02, 95% CI, 0.73-1.42, p = 0.91). The benefit of an ERV strategy was similar (HR [DM] 0.62; HR [NDM] 0.75, p = 0.58). Even after adjusting for the imbalance in CABG rates, 1-year mortality was not associated with DM. CONCLUSION: Diabetes mellitus is not a predictor of 1-year mortality in CS after AMI. The benefit from an ERV strategy is similar for DM and NDM. The management strategies and influence of DM on mortality in CS deserve further evaluation.

Aged↗

PubMed2005

Functional status and quality of life after emergency revascularization for cardiogenic shock complicating acute myocardial infarction.

OBJECTIVES: Our goal was to describe the functional status of cardiogenic shock survivors, identify the correlates of cardiogenic shock, and compare global quality of life and functional status of patients randomly assigned to treatment with emergency revascularization (ERV) versus initial medical stabilization (IMS). BACKGROUND: Historically, the hospital survival rate of patients with cardiogenic shock complicating acute myocardial infarction (MI) has been very low. Shock survivors are salvaged from a critically ill state, and their later functional status is not well documented. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial showed significantly improved one-year survival after ERV compared with IMS. METHODS: The SHOCK trial survivors completed interviews at 2 weeks after discharge and at 6 and 12 months after MI. Functional status assessment included the Multidimensional Index of Life Quality and New York Heart Association (NYHA) congestive heart failure functional class. RESULTS: Eighty-seven percent of one-year survivors of the SHOCK trial were in NYHA functional class I or II. Between two weeks after discharge and one year after MI, improvement was similar in the two treatment groups (18% overall), but fewer patients remained stable (44% vs. 71%), and more patients worsened or died (34% vs. 15%) in the IMS group compared with those assigned to ERV. Assignment to ERV was the only independent predictor of outcome at one year. CONCLUSIONS: Although one-year mortality after ERV is still high (54%), most survivors have good functional status. The ERV patients have a lower rate of deterioration than IMS patients. The level of recovery for shock patients undergoing ERV is similar to that of historical controls not in cardiogenic shock undergoing elective revascularization.

Angioplasty, Balloon, Coronary↗

PubMed2005

Usefulness of tissue Doppler imaging in the diagnosis and prognosis of acute right ventricular infarction with inferior wall acute left ventricular infarction.

Tissue Doppler (TD) imaging is a novel echocardiographic technique that measures myocardial velocities. However, there are sparse data on TD imaging of the right ventricular (RV) free wall in the diagnosis and prognosis of RV myocardial infarction (MI) in inferior wall left ventricular MI. Fifty patients who had left ventricular MI underwent TD echocardiography and angiography within 48 hours of MI. For diagnosis, the ability of RV TD imaging to detect RV MI was assessed using coronary angiography as the reference standard. For prognosis, the ability of TD detection of RV dysfunction to predict cardiac death or rehospitalization at 1 year was determined. For diagnosis, the univariate predictors of RV MI included RV diastolic dimension (p = 0.001), TD imaging of tricuspid annular systolic velocity (p = 0.001), and early diastolic velocity (p = 0.002). On multivariate analysis, systolic annular velocity (p = 0.04) and RV dimension (p = 0.05) predicted RV MI. For prognosis, nonculprit coronary artery disease (p = 0.003), TD imaging of RV systolic annular velocity (p = 0.005), and early diastolic velocity (p = 0.01) were among the univariate predictors of cardiac death or rehospitalization. On multivariate analysis, nonculprit coronary artery disease (p = 0.02) and TD imaging of systolic annular velocity (p = 0.04) were independent predictors of outcome. Decreased RV systolic annular velocity on TD images detects RV MI in first left ventricular acute inferior MI and predicts cardiac death or rehospitalization at 1 year.

Acute Disease↗

PubMed2004

The profile of cardiac patients with renal artery stenosis.

OBJECTIVES: We examined the prevalence and severity of renal artery stenosis (RAS) in patients undergoing cardiac catheterization who were deemed at risk for RAS based on clinical or laboratory criteria for study entry, but who had not previously been suspected of having RAS. BACKGROUND: The diagnosis of atherosclerotic RAS remains problematic because its clinical manifestations are nonspecific. METHODS: Consecutive patients undergoing non-emergent cardiac catheterization at a single institution during a 12-month period were evaluated using standardized clinical, laboratory, and angiographic criteria. Patients exhibiting at least one of four predefined selection criteria (severe hypertension, unexplained renal dysfunction, acute pulmonary edema with hypertension, or severe atherosclerosis) were prospectively registered and underwent coincident diagnostic renal angiography. RESULTS: Renal angiography was performed in 851 patients and was diagnostic in 837. Angiographically evident renal atherosclerosis was present in 39% of the population, with RAS > or =50% in 120 (14.3%) and severe stenosis (> or =70%) in 61 (7.3%). Severe stenosis was present in 48 (7%) patients with severe atherosclerosis, 38 (16%) with renal dysfunction, 25 (9%) with hypertension, and 2 (22%) with acute pulmonary edema with hypertension. The prevalence was higher in those exhibiting multiple selection criteria. In a multivariate model, severe RAS was associated with age, female gender, reduced creatinine clearance, increased systolic blood pressure, and peripheral or carotid artery disease. CONCLUSIONS: In a population at risk of, but not previously suspected of having RAS, severe RAS is associated with simple and readily determined clinical and laboratory patient characteristics. These data facilitate focused application of diagnostic renal angiography.

Adult↗

PubMed2003

A score predicts failure of reperfusion after fibrinolytic therapy for acute myocardial infarction.

BACKGROUND: A rapid, accurate, noninvasive means of predicting the likelihood of failure to achieve Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow within 90 minutes after the start of fibrinolysis with streptokinase could help to identify patients who might benefit from additional therapies that aim to preserve myocytes. METHODS: We measured ST recovery, which was assessed as the sum of ST deviation on a 12-lead electrocardiogram, and blood levels of the myocardial proteins, troponin T, creatine kinase myocardial band (CK-MB), and myoglobin before and 60 minutes after commencing streptokinase infused for 30 to 60 minutes in 107 patients, who presented within 12 hours of symptom onset and underwent angiography at 90 minutes. RESULTS: At 90 minutes, 56% of patients (95% CI 46-66) had TIMI-3 flow. The baseline levels of troponin T, CK-MB, and myoglobin were more commonly below the discrimination values in patients with TIMI-3 flow than in patients without TIMI-3 flow (all P <.005). On multivariate analysis, the factors associated with failure to achieve TIMI-3 flow were ST recovery of <70% (P =.009), a 60-minute/baseline troponin T ratio of < or =5 (P =.0004), a baseline CK-MB level of >4 microg/L (P =.039), or a baseline myoglobin level of >85 microg/L (P =.048). Age and a history of myocardial infarction were added into the multivariate model, and a risk score was developed to predict the likelihood of failure to achieve TIMI-3 flow. A score of < or =2 excluded failure to achieve TIMI-3 flow with 96% accuracy, and a score of > or =7 predicted failure to achieve TIMI-3 flow with 90% accuracy. CONCLUSION: Failure to achieve TIMI-3 flow in the infarct-related artery within 90 minutes after the start of fibrinolysis can be accurately predicted at approximately 60 minutes by a score incorporating clinical variables, ST recovery, and the 60-minute/baseline ratios of troponin T, CK-MB, and/or myoglobin levels. This score may facilitate triage of patients at 60 minutes after fibrinolysis to additional reperfusion therapies.

Biomarkers↗

PubMed2002

Modeling hair cell tuning by expression gradients of potassium channel beta subunits.

The receptor potential of sensory hair cells arises from the gating of mechanosensitive cation channels, but its amplitude and time course also depend on the number and kinetics of voltage-gated ion channels in each cell. Prominent among these are "BK" potassium channels encoded by the slo gene that support electrical tuning in some hair cells. Hair cells tuned to low frequencies have slowly gating BK channels, whereas those of higher-frequency hair cells gate more rapidly. Alternative splicing of the slo gene mRNA that encodes the pore-forming alpha subunit can alter BK channel kinetics, and gating is dramatically slowed by coexpression with modulatory beta subunits. The effect of the beta subunit is consistent with low-frequency tuning, and beta mRNA is expressed at highest levels in the low frequency apex of the bird's auditory epithelium. How might an expression gradient of beta subunits contribute to hair cell tuning? The present work uses a computational model of hair cell-tuning based on the functional properties of BK channels expressed from hair cell alpha and beta slo cDNA. The model reveals that a limited tonotopic gradient could be achieved simply by altering the fraction of BK channels in each hair cell that are combined with beta subunits. However, complete coverage of the tuning spectrum requires kinetic variants in addition to those modeled here.

Allosteric Regulation↗

PubMed2002

Increased myocardial ischemia after food is not explained by endothelial dysfunction.

BACKGROUND: Recent studies suggest that a high-fat meal can impair endothelial function. The aim of this study was to determine whether greater myocardial ischemia after either a low-fat or a high-fat meal is associated with an increase in brachial artery endothelial dysfunction. METHODS: Twenty subjects with coronary artery disease and > or =1-mm ST-segment depression during exercise were studied. In a randomized, double-blind, crossover design, ST-segment changes during treadmill exercise and brachial artery diameter and flow-mediated dilation were measured before and 3 hours after a low-fat milkshake meal or the same meal supplemented with 64 grams of cooked fat. RESULTS: After the low-fat but not the high-fat meal, resting brachial artery diameter decreased (before meal 4.72 +/-0.50 mm, after low fat meal 4.62 +/-0.49 mm, P =.001; after high fat meal 4.70 +/-0.51 mm, not significant). High-flow brachial artery diameter was similar before (4.81 +/- 0.48 mm) and after the low-fat (4.82 +/- 0.48 mm) and high-fat (4.84 +/- 0.48 mm) meals (P >.05 for all). Brachial artery flow-mediated dilation was not impaired after either meal. Exercise duration decreased more after the low-fat meal (mean change 39 seconds, 95% CI -14 to -63 seconds, P =.004) than after the high-fat meal (-7 seconds, 95% CI +19 to -34 seconds, not significant). ST-segment depression during equivalent exercise was greater after compared with before both meals (before meals 1.03 +/- 0.69 mm, after low fat 1.27 +/- 0.80 mm, P =.03; after high fat 1.24 +/- 0.74 mm, P =.04). CONCLUSIONS: Increased myocardial ischemia after food is caused by mechanisms other than endothelial dysfunction and by meal components other than cooked fat.

Adult↗

PubMedDate not supplied

Randomized, double-blind comparison of acute beta1-blockade with 50 mg metoprolol tartrate vs 25 mg carvedilol in normal subjects.

Differential efficacy of immediate-release metoprolol tartrate and carvedilol in the treatment of congestive heart failure remains a subject of ongoing debate. The degree of beta1-blockade can be assessed by percentage reduction of exercise heart rate. Twelve healthy subjects underwent symptom-limited cardiopulmonary exercise testing repeated weekly and 2 hours after randomized, double-blind administration of 50 mg metoprolol tartrate vs 25 mg carvedilol. Baseline heart rate, heart rate at 40% and 70% peak O2 consumption, and maximal exercise were significantly blunted more by metoprolol tartrate than by carvedilol (P<.05 for all). Peak O2 consumption was significantly reduced by metoprolol tartrate (P<.03) but not by carvedilol (P=.054). The change in O2 consumption was significantly correlated with the degree of beta1-blockade (r =0.45; P<.05). In healthy subjects, a higher degree of beta1-blockade is achieved with 50 mg metoprolol tartrate compared with 25 mg carvedilol.

Adrenergic alpha-Antagonists↗