The word variability has a pejorative tone for clinicians and scientists as its meaning encompass... more The word variability has a pejorative tone for clinicians and scientists as its meaning encompasses a likelihood to change which suggests an unreliable measurement. The concern about the term variability is also based on the use of the term variable, which in mathematics is capable of assuming any value. In the field of hypertension, variability is expected and is often viewed as an annoyance. Not withstanding the data that blood pressure variability can be a predictor of cardiovascular events, clinicians and patients want a definitive number to know whether or not hypertension exists, whether antihypertensive therapy should be initiated, and to what target blood pressure should antihypertensive drugs dosage be increased or decreased. The question of blood pressure variability is the subject of the article by Myers and Kaczorowski in this issue of Hypertension. A large number of measurements will, of course, ensure the precision of the measurement which for blood pressure means ambulatory 24-hour BP measurement (ABPM). ABPM permits the best approximation of the average BP load placed on the vasculature and organs vulnerable to hypertensiveinduced changes. ABPM also provides data on nocturnal blood pressure, which is not available in either office or home blood pressure measurement and is a predictor of adverse outcome. Clinical utility requires alternatives, which currently are office or home blood pressure measurement. Automated office blood pressure measurement (AoBP) is the measurement of blood pressure with an automatic device without the health care provider’s presence in the room. AoBP removes many of the factors, which can influence blood pressure in the clinic/office such as interaction with physician or healthcare provider, observer recording of digit preference, etc. Home blood pressure measurement removes the emotional excitement or alerting reaction associated with attending the office of the healthcare provider and may represent a better approximation of usual blood pressure. Furthermore, home BP measurement is a significant predictor of subsequent cardiovascular events. If this is the case, then might the perceived lower variability of home blood pressure obviate the need for measurement of office/ clinic blood pressure? Home blood pressure, however, is still variable with a wide spectrum of conditions associated with home BP variability (Figure). Increased age, female sex, body weight, cigarette consumption, alcohol, psychological stresses at home, vasoreactivity (as exemplified by response to cold exposure), target organ diseases such as left ventricular hypertrophy, chronic kidney disease and peripheral vascular disease, subclinical atherosclerotic disease in the larger arteries as well as certain antihypertensive drugs, all contribute to blood pressure variability. In addition, time of day, day of week, and season of year all contribute to blood pressure variability. So how does AoBP compare with home blood pressure from the perspective of BP variability? In this issue of Hypertension, Myers and Kaczorowski sought to answer that question. They studied 300 people referred for ABPM who also had AoBP and home BP measurements. They found that blood pressure variability of AoBP was similar to that of home BP. The interquartile ranges (25th to 75th percentile) for AoBP and home blood pressure were similar. The ranges for systolic BP measured by AoBP and home BP were similar. Coefficients of variation for systolic BP for home BP and AoBP were 11.8% and 12.0%, respectively, which were not significantly different. Taken together, these data convincingly demonstrate that the variability of AoBP is similar to that of home BP. Thus, guidelines should not dismiss AoBP measurements because it is more variable or consider it less trust worthy than home BP measurements. There can be an argument made for home BP on the basis of cost efficiency. Such a proposal is presented in the recent The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). In those guidelines, they proposed home BP because of the hurdles, such as difficulty in securing the space and the need of patient guidance, AOBP has been seldom adopted in Japan. Guidelines that prefer home blood pressure measurement for the diagnosis and management of hypertension presuppose that their population can afford to purchase home blood pressure machines and are knowledgeable about approved machines and their proper usage for accurate blood pressure measurement. In addition, they may not provide guidance on the preferred approach for measurement of blood pressure in the office or clinic. Unfortunately, the debate about AoBP versus home BP does not end. Considering that ABPM is usually accepted as a more accurate method to diagnose hypertension, the data in this study do not provide comfort because of the relatively low correlation between ABPM and either AoBP or home BP. One problem with research on variability is…
The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejectio... more The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejection fraction (HFpEF) has recently been examined by machine learning techniques but studies appear to have produced discordant results. The objective of this study is to synthesize the types of HFpEF by examining their features and relating them to phenotypes with adverse prognosis. A systematic search was conducted using the search terms "Diastolic Heart Failure" OR "heart failure with preserved ejection fraction" OR "heart failure with normal ejection fraction" OR "HFpEF" AND "machine learning" OR "artificial intelligence" OR 'computational biology'. Ten studies were identified and they varied in their prevalence of ten clinical variables: age, sex, body mass index (BMI) or obesity, hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease or symptom severity (NYHA class or BNP). The clinical findings associated with the different phenotypes in > 85 % of studies were age, hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity; an adverse outcome was in 65 % to 85 % of studies identified diabetes mellitus and female sex and in less than 65 % of studies was body mass index or obesity, and coronary artery disease. COPD was a relevant factor in only 33 % of studies. Adverse clinical outcome - death or admission to hospital (for heart failure) defined phenogroups with the worst outcome. Combining the 4 studies that calculated the MAGGIC score showed a significant (p<0.05) linear relationship between MAGGIC score and outcome, using the one-year event rate. A new score based on strength of the evidence of the HFpEF studies analyzed here, using 9 variables (eliminating COPD), showed a significant (p<0.009) linear relationship with one-year event rate. Three studies examined biomarkers in detail and the ones most prominently related to outcome or consistently found in the studies were GDF15, FABP4, FGF23, sST2, renin and TNF. The dominant factors that identified phenotypes of HFpEF with adverse outcome were hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity. A new simplified score, based on clinical factors, was proposed to assess prognosis in HFpEF. Several biomarkers were consistently elevated in phenogroups with adverse outcomes and may indicate the underlying mechanism or pathophysiology specific for phenotypes with an adverse prognosis.
In-vitro evidence of sorption of nitroglycerin (NTG) to polyvinylchloride (PVC) containers sugges... more In-vitro evidence of sorption of nitroglycerin (NTG) to polyvinylchloride (PVC) containers suggests that these containers may deliver less nitroglycerin to the patient than glass containers. Sorption of NTG to the PVC container may result in hemodynamic changes in the patient when a fresh solution of NTG is prepared and administered from a PVC container. This study was designed as a prospective, randomized trial to measure the hemodynamic response in patients receiving NTG in glass or PVC containers, during the first hour after a container exchange. Patients admitted to the coronary care unit in a University hospital with chest pain considered to be due to unstable angina or acute myocardial infarction were eligible. Patients who received other vasoactive drugs within one hour of container exchanges were excluded. Systolic and diastolic blood pressures, and heart rate were measured at baseline and at intervals for one hour following a container exchange. Twenty patients completed the study. There were no significant changes with time in either group (ANOVA, p > 0.05) with respect to systolic, diastolic, or mean arterial blood pressure or heart rate. No chest pain occurred during the 60 minutes following the container exchange in either group. We conclude that NTG can be administered safely and effectively in PVC containers to patients with unstable angina or acute myocardial infarction. However, it remains possible that changes in hemodynamic status could occur in patients on NTG if a change in container type (i.e., from PVC to glass or vice versa) is made during the course of therapy.
Objective: To investigate whether serum insulin, insulin-like-growth factor I (IGF-I),insulin-lik... more Objective: To investigate whether serum insulin, insulin-like-growth factor I (IGF-I),insulin-like-growth factor II (IGF-II) and growth hormone (GH)--each of which is a known trophic factor in vitro for the cardiomyocyte, and levels of which can be altered in noninsulin-dependent diabetes mellitus (NIDDM)--related of left ventricular (LV) mass in patients with NIDDM. Design: Observational study. Setting: University teaching hospital. Patients and methods: Patients with NIDDM without signs, symptoms or past history of hypertension, ischemic or valvular heart disease, or heart failure were recruited from the diabetes clinic of an university hospital. Fasting patients had blood drawn for determination of serum insulin, IGF-I, IGF-II and GH by radioimmunoassay. Height, weight, and blood pressure were recorded. An electrocardiogram was obtained and echocardiography were performed for calculation of LV mass. Results: Patients' average age was 54.7 +/-1.6 years, and duration of NIDDM was 9.3 +/- 1.2 years. LV mass was 113.7 +/- 8.9 g/m2 in men (n=13) and 104.1 +/- 10.8 g/m2 in women (n=10). Serum insulin was 25.3 +/- ng/mL, IGF-I was 255 +/- 15 ng/mL, IGF-II was 0.62 +/- 0.05 microg/mL and GH was 5.4 +/- 0.5 ng/mL. There were no significant differences in LV mass among patients with serum insulin, IGF-I, IGF-II or GH in the upper compared with the lower 50th percentile. There were no significant differences in serum insulin, IGF-I, IGF-II or GH among patients in the upper compared with the lower 50th percentile for LV mass. Standardization of LV mass for body size, either by height or body surface area, did not alter the relationships. The correlation coefficients from linear least squares regression analysis between these hormones and LV mass were low (r<0.003), suggesting that even much larger sample sizes might not alter these findings. Conclusions: These data suggest that circulating total serum concentrations of growth factor (insulin, IGF-I, IGF-II and GH) are not determinants of LV mass in nonhypertensive patients with NIDDM.
Objective: To provide Canadian physicians with comprehensive, evidence-based guidelines for the n... more Objective: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. Options: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. Outcomes: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. Evidence: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. Values: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. Benefits, harms and costs: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. Recommendation: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. Validation: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.
Objective: To assess the degree of association of abdominal obesity with blood pressure and plasm... more Objective: To assess the degree of association of abdominal obesity with blood pressure and plasma lipid levels and to determine which anthropometric measures of obesity are most closely associated with these cardiovascular risk factors. Design: Population-based, cross-sectional surveys. Setting: Five Canadian provinces (Alberta, Manitoba, Ontario, Quebec and Saskatchewan) between 1989 and 1992. Participants: A probability sample of 16,007 men and women aged 18 to 74 was selected using health insurance registration files in each province and invited to participate. A complete set of measurements was available for 8974 (56%) adults. Outcome measures: Initially, simple correlation analyses by age and sex were performed between the anthropometric variables-body mass index, waist circumference (WC), hip circumference (HC), ratio of waist to hip circumference (WHR)- and cardiovascular disease risk variables-systolic blood pressure (SBP), diastolic blood pressure (DBP), levels of total cholesterol (TC), low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TRIG) and the TC/HDL ratio. Canonical correlation analyses were performed to determine the multivariate associations between the anthropometric and risk variables. Results: The simple correlations between anthropometric variables and cardiovascular disease risk variables were highest for SBP; moderate for DBP, HDL, TRIG and TC/HDL; and lowest for LDL and TC. Of the anthropometric variables, WC demonstrated the greatest correlations with the risk variables. The first canonical correlations were significant (p < 0.0001) in men (0.58) and women (0.61) of all ages. Of the anthropometric variables, WC consistently demonstrated the highest loading values in the first canonical variable in men (0.56) and women (0.59). Of the risk variables in both sexes, the loadings of TRIG were generally the largest, those of HDL, SBP, DBP intermediate and those of LDL the smallest. In men, the strength of these associations generally decreased with age, whereas in women they peaked in the 35-54 year age group. Conclusion: Considerable association was seen between measures of abdominal obesity and blood pressure and plasma lipid levels. WC is the measure of abdominal obesity most highly correlated with these cardiovascular disease risk factors.
Objectives: To provide Canadian physicians with a standard definition of hypertension in pregnanc... more Objectives: To provide Canadian physicians with a standard definition of hypertension in pregnancy, recommendations for laboratory investigations and tests for the assessment and management of hypertensive disorders in pregnancy, and a classification of such disorders. Options: To improve or not improve Canadian uniformity and standardization in the investigation and classification of hypertensive disorders in pregnancy. Outcomes: 1) Accuracy, reliability and practicality of diagnostic clinical criteria for hypertensive disorders in pregnancy. 2) Laboratory tests useful to determine severity and prognosis of disorders as measured by maternal and neonatal adverse outcomes. 3) A classification of disorders for use by Canadian physicians to facilitate uniformity and diffusion of research through a common language. Evidence: Articles on hypertensive disorders in pregnancy published from 1966 to 1996, retrieved through MEDLINE search, related to definitions, tests, diagnostic criteria and classification, as well as documents on diagnosis and classification from authorities in the United States, Europe and Australia and from special interest groups. Values: High priority was given to the principle of preventing adverse maternal and neonatal outcomes through the provision of diagnostic criteria for severity and prognosis and through dissemination of reliable and pertinent information and research results using a common language. BENEFITS, HARMS AND COST: Higher degree of vigilance in diagnosing hypertensive disorders in pregnancy, allowing for earlier assessment and intervention, and more efficient dissemination of comparative information through common language. No harm or added cost is perceived at this time. Recommendations: (1) A diastolic blood pressure of 90 mm Hg or more should be the criterion for a diagnosis of hypertension in pregnancy and should trigger investigation and management. Except for very high diastolic readings (110 mm Hg or more), all diastolic readings of 90 mm Hg or more should be confirmed after 4 hours. (2) A regularly calibrated mercury sphygmomanometer, with an appropriate-sized cuff, is the instrument of choice. A rest period of 10 minutes should be allowed before taking the blood pressure. The woman should be sitting upright and the cuff positioned at the level of the heart. (3) Both Korotkoff phase IV and V sounds should be recorded, but the phase IV sound should be used for initiating clinical investigation and management. (4) A urine protein level of more than 0.3 g/d should be the criterion for a diagnosis of proteinuria; 24-hour urine collection should be the standard method for determining proteinuria. (5) Edema and weight gain should not be used as diagnostic criteria. (6) Hypertensive disorders diagnosed during pregnancy should be classified as pre-existing hypertension; gestational hypertension with or without proteinuria; pre-existing hypertension with superimposed gestational hypertension with proteinuria; and unclassifiable antenatally but final classification 42 days after delivery. Validation: Except for expert opinions and reviews solicited for this project, these recommendations need to be field tested and validated in Canada. Guidelines endorsed by the Canadian Hypertension Society and the Society of Obstetricians and Gynaecologists of Canada.
OBJECTIVE Heart failure with preserved ejection (HFpEF) represents nearly half of all patients wi... more OBJECTIVE Heart failure with preserved ejection (HFpEF) represents nearly half of all patients with heart failure (HF). The objective of this study was to determine whether patient characteristics identify discrete kinds of HFpEF. METHODS Data were collected on 196 patients with HFpEF in a non-hospitalized setting. Clinical and laboratory variables were collected, and 47 candidate variables were examined by the unsupervised clustering strategy partitioning around medoids. The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was calculated. Follow-up data on all-cause mortality, cardiovascular mortality, and HF exacerbation, were collected and were not part of the data used to identify subgroups. RESULTS Six significantly different groups or clusters were found. There were three groups of women (i) individuals with a low proportion of vascular risk factors (HFpEF1) (ii) individuals with a high proportion of hypertension and diabetes, but lower proportion of kidney disease and diastolic dysfunction (HFpEF3) (iii) older individuals with high rates of atrial fibrillation (AF), chronic kidney disease. They had the worst long-term outcomes (HFpEF4). There were three groups of men (i) individuals with a high proportion of coronary artery disease (CAD), dyslipidemia, higher serum creatinine, and diastolic dysfunction (HFpEF2) (ii) individuals with highest BMI, and high proportion of CAD, obstructive sleep apnea, and poorly controlled diabetes (HFpEF5) (iii) individuals with high rates of AF, elevated BNP, biventricular remodeling (HFpEF6). They had a high cardiovascular mortality. CONCLUSIONS HFpEF consists of a heterogenous group of individuals with six distinct clinical subsets that have different long-term outcomes.
In 812 patients who underwent routine preoperative electrocardiography a mean of 24.6 months afte... more In 812 patients who underwent routine preoperative electrocardiography a mean of 24.6 months after undergoing electrocardiography at the same institution, the frequency of new abnormalities was estimated to evaluate the cost-effectiveness of this procedure prior to an operation. New abnormalities were judged to be either relevant or irrelevant to the assessment of operative risk, depending upon their previously demonstrated correlation with operative and postoperative morbidity and mortality. Since new abnormalities, especially new relevant abnormalities, were found to be relatively infrequent, the cost-effectiveness of routine preoperative electrocardiography was considered to be low. The evidence suggested that when a previous tracing exists preoperative electrocardiography is most clearly indicated for patients who are 60 years of age or older or whose previous tracing exhibited abnormalities. However, further research is required to develop more sensitive and specific protocols, and to evaluate the role of repeat electrocardiography in clinical decision-making.
Background and Objective: Palpitations are a common symptom that may indicate cardiac arrhythmias... more Background and Objective: Palpitations are a common symptom that may indicate cardiac arrhythmias, be a somatic complaint in anxiety disorders, and can be present in patients without either condition. The objective of this review was to explore the pathways and fundamental mechanisms through which individuals appreciate palpitations. Observations: Cardiac afferents provide beat-to-beat sensory information on the heart to the spinal cord, brain stem, and higher brain centers. Cardioception, a subset of interoception (‘the physiological sense of the condition of the body’), refers to sensing of the heartbeat. High cardioception is present in persons with lower body mass index, lower percentages of body fat, and anxiety disorders. Low cardioception (lower interoceptive awareness) is associated with psychiatric disorders, such as depression, personality disorders, and schizophrenia. CNS sites associated with heartbeat detection have been identified by functional magnetic resonance imaging studies and heartbeat-evoked electroencephalogram potentials. The right insula, cingulate gyrus, somatomotor and somatosensory cortices nucleus accumbens, left subthalamic nucleus, and left ventral capsule/striatum are implicated in both palpitations and heartbeat detection. Involvement of the brain as a primary modulator of palpitations rests on the data that various areas of the brain are activated in association with cardioception, the ability of focal brain stimulation to induce palpitations, the ability of central alpha receptor agonists and antagonists to modulate palpitations, and suppression of palpitations by transcranial repetitive magnetic stimulation (rTMS). Conclusions: Palpitations should be viewed as a pathway extending from the heart to the brain. Palpitations are, in part, a reflection of an individual’s cardioception awareness, which is modulated by body size, percentage of body fat, and psychological or psychiatric conditions. Palpitations can originate in the brain and involve central neurotransmitters. Treatment of palpitations unrelated to cardiac arrhythmias or anxiety disorders should consider the use of central alpha-2 agonists and possibly rTMS.
The word variability has a pejorative tone for clinicians and scientists as its meaning encompass... more The word variability has a pejorative tone for clinicians and scientists as its meaning encompasses a likelihood to change which suggests an unreliable measurement. The concern about the term variability is also based on the use of the term variable, which in mathematics is capable of assuming any value. In the field of hypertension, variability is expected and is often viewed as an annoyance. Not withstanding the data that blood pressure variability can be a predictor of cardiovascular events, clinicians and patients want a definitive number to know whether or not hypertension exists, whether antihypertensive therapy should be initiated, and to what target blood pressure should antihypertensive drugs dosage be increased or decreased. The question of blood pressure variability is the subject of the article by Myers and Kaczorowski in this issue of Hypertension. A large number of measurements will, of course, ensure the precision of the measurement which for blood pressure means ambulatory 24-hour BP measurement (ABPM). ABPM permits the best approximation of the average BP load placed on the vasculature and organs vulnerable to hypertensiveinduced changes. ABPM also provides data on nocturnal blood pressure, which is not available in either office or home blood pressure measurement and is a predictor of adverse outcome. Clinical utility requires alternatives, which currently are office or home blood pressure measurement. Automated office blood pressure measurement (AoBP) is the measurement of blood pressure with an automatic device without the health care provider’s presence in the room. AoBP removes many of the factors, which can influence blood pressure in the clinic/office such as interaction with physician or healthcare provider, observer recording of digit preference, etc. Home blood pressure measurement removes the emotional excitement or alerting reaction associated with attending the office of the healthcare provider and may represent a better approximation of usual blood pressure. Furthermore, home BP measurement is a significant predictor of subsequent cardiovascular events. If this is the case, then might the perceived lower variability of home blood pressure obviate the need for measurement of office/ clinic blood pressure? Home blood pressure, however, is still variable with a wide spectrum of conditions associated with home BP variability (Figure). Increased age, female sex, body weight, cigarette consumption, alcohol, psychological stresses at home, vasoreactivity (as exemplified by response to cold exposure), target organ diseases such as left ventricular hypertrophy, chronic kidney disease and peripheral vascular disease, subclinical atherosclerotic disease in the larger arteries as well as certain antihypertensive drugs, all contribute to blood pressure variability. In addition, time of day, day of week, and season of year all contribute to blood pressure variability. So how does AoBP compare with home blood pressure from the perspective of BP variability? In this issue of Hypertension, Myers and Kaczorowski sought to answer that question. They studied 300 people referred for ABPM who also had AoBP and home BP measurements. They found that blood pressure variability of AoBP was similar to that of home BP. The interquartile ranges (25th to 75th percentile) for AoBP and home blood pressure were similar. The ranges for systolic BP measured by AoBP and home BP were similar. Coefficients of variation for systolic BP for home BP and AoBP were 11.8% and 12.0%, respectively, which were not significantly different. Taken together, these data convincingly demonstrate that the variability of AoBP is similar to that of home BP. Thus, guidelines should not dismiss AoBP measurements because it is more variable or consider it less trust worthy than home BP measurements. There can be an argument made for home BP on the basis of cost efficiency. Such a proposal is presented in the recent The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). In those guidelines, they proposed home BP because of the hurdles, such as difficulty in securing the space and the need of patient guidance, AOBP has been seldom adopted in Japan. Guidelines that prefer home blood pressure measurement for the diagnosis and management of hypertension presuppose that their population can afford to purchase home blood pressure machines and are knowledgeable about approved machines and their proper usage for accurate blood pressure measurement. In addition, they may not provide guidance on the preferred approach for measurement of blood pressure in the office or clinic. Unfortunately, the debate about AoBP versus home BP does not end. Considering that ABPM is usually accepted as a more accurate method to diagnose hypertension, the data in this study do not provide comfort because of the relatively low correlation between ABPM and either AoBP or home BP. One problem with research on variability is…
The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejectio... more The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejection fraction (HFpEF) has recently been examined by machine learning techniques but studies appear to have produced discordant results. The objective of this study is to synthesize the types of HFpEF by examining their features and relating them to phenotypes with adverse prognosis. A systematic search was conducted using the search terms "Diastolic Heart Failure" OR "heart failure with preserved ejection fraction" OR "heart failure with normal ejection fraction" OR "HFpEF" AND "machine learning" OR "artificial intelligence" OR 'computational biology'. Ten studies were identified and they varied in their prevalence of ten clinical variables: age, sex, body mass index (BMI) or obesity, hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease or symptom severity (NYHA class or BNP). The clinical findings associated with the different phenotypes in > 85 % of studies were age, hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity; an adverse outcome was in 65 % to 85 % of studies identified diabetes mellitus and female sex and in less than 65 % of studies was body mass index or obesity, and coronary artery disease. COPD was a relevant factor in only 33 % of studies. Adverse clinical outcome - death or admission to hospital (for heart failure) defined phenogroups with the worst outcome. Combining the 4 studies that calculated the MAGGIC score showed a significant (p<0.05) linear relationship between MAGGIC score and outcome, using the one-year event rate. A new score based on strength of the evidence of the HFpEF studies analyzed here, using 9 variables (eliminating COPD), showed a significant (p<0.009) linear relationship with one-year event rate. Three studies examined biomarkers in detail and the ones most prominently related to outcome or consistently found in the studies were GDF15, FABP4, FGF23, sST2, renin and TNF. The dominant factors that identified phenotypes of HFpEF with adverse outcome were hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity. A new simplified score, based on clinical factors, was proposed to assess prognosis in HFpEF. Several biomarkers were consistently elevated in phenogroups with adverse outcomes and may indicate the underlying mechanism or pathophysiology specific for phenotypes with an adverse prognosis.
In-vitro evidence of sorption of nitroglycerin (NTG) to polyvinylchloride (PVC) containers sugges... more In-vitro evidence of sorption of nitroglycerin (NTG) to polyvinylchloride (PVC) containers suggests that these containers may deliver less nitroglycerin to the patient than glass containers. Sorption of NTG to the PVC container may result in hemodynamic changes in the patient when a fresh solution of NTG is prepared and administered from a PVC container. This study was designed as a prospective, randomized trial to measure the hemodynamic response in patients receiving NTG in glass or PVC containers, during the first hour after a container exchange. Patients admitted to the coronary care unit in a University hospital with chest pain considered to be due to unstable angina or acute myocardial infarction were eligible. Patients who received other vasoactive drugs within one hour of container exchanges were excluded. Systolic and diastolic blood pressures, and heart rate were measured at baseline and at intervals for one hour following a container exchange. Twenty patients completed the study. There were no significant changes with time in either group (ANOVA, p > 0.05) with respect to systolic, diastolic, or mean arterial blood pressure or heart rate. No chest pain occurred during the 60 minutes following the container exchange in either group. We conclude that NTG can be administered safely and effectively in PVC containers to patients with unstable angina or acute myocardial infarction. However, it remains possible that changes in hemodynamic status could occur in patients on NTG if a change in container type (i.e., from PVC to glass or vice versa) is made during the course of therapy.
Objective: To investigate whether serum insulin, insulin-like-growth factor I (IGF-I),insulin-lik... more Objective: To investigate whether serum insulin, insulin-like-growth factor I (IGF-I),insulin-like-growth factor II (IGF-II) and growth hormone (GH)--each of which is a known trophic factor in vitro for the cardiomyocyte, and levels of which can be altered in noninsulin-dependent diabetes mellitus (NIDDM)--related of left ventricular (LV) mass in patients with NIDDM. Design: Observational study. Setting: University teaching hospital. Patients and methods: Patients with NIDDM without signs, symptoms or past history of hypertension, ischemic or valvular heart disease, or heart failure were recruited from the diabetes clinic of an university hospital. Fasting patients had blood drawn for determination of serum insulin, IGF-I, IGF-II and GH by radioimmunoassay. Height, weight, and blood pressure were recorded. An electrocardiogram was obtained and echocardiography were performed for calculation of LV mass. Results: Patients' average age was 54.7 +/-1.6 years, and duration of NIDDM was 9.3 +/- 1.2 years. LV mass was 113.7 +/- 8.9 g/m2 in men (n=13) and 104.1 +/- 10.8 g/m2 in women (n=10). Serum insulin was 25.3 +/- ng/mL, IGF-I was 255 +/- 15 ng/mL, IGF-II was 0.62 +/- 0.05 microg/mL and GH was 5.4 +/- 0.5 ng/mL. There were no significant differences in LV mass among patients with serum insulin, IGF-I, IGF-II or GH in the upper compared with the lower 50th percentile. There were no significant differences in serum insulin, IGF-I, IGF-II or GH among patients in the upper compared with the lower 50th percentile for LV mass. Standardization of LV mass for body size, either by height or body surface area, did not alter the relationships. The correlation coefficients from linear least squares regression analysis between these hormones and LV mass were low (r<0.003), suggesting that even much larger sample sizes might not alter these findings. Conclusions: These data suggest that circulating total serum concentrations of growth factor (insulin, IGF-I, IGF-II and GH) are not determinants of LV mass in nonhypertensive patients with NIDDM.
Objective: To provide Canadian physicians with comprehensive, evidence-based guidelines for the n... more Objective: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. Options: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. Outcomes: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. Evidence: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. Values: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. Benefits, harms and costs: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. Recommendation: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. Validation: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.
Objective: To assess the degree of association of abdominal obesity with blood pressure and plasm... more Objective: To assess the degree of association of abdominal obesity with blood pressure and plasma lipid levels and to determine which anthropometric measures of obesity are most closely associated with these cardiovascular risk factors. Design: Population-based, cross-sectional surveys. Setting: Five Canadian provinces (Alberta, Manitoba, Ontario, Quebec and Saskatchewan) between 1989 and 1992. Participants: A probability sample of 16,007 men and women aged 18 to 74 was selected using health insurance registration files in each province and invited to participate. A complete set of measurements was available for 8974 (56%) adults. Outcome measures: Initially, simple correlation analyses by age and sex were performed between the anthropometric variables-body mass index, waist circumference (WC), hip circumference (HC), ratio of waist to hip circumference (WHR)- and cardiovascular disease risk variables-systolic blood pressure (SBP), diastolic blood pressure (DBP), levels of total cholesterol (TC), low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TRIG) and the TC/HDL ratio. Canonical correlation analyses were performed to determine the multivariate associations between the anthropometric and risk variables. Results: The simple correlations between anthropometric variables and cardiovascular disease risk variables were highest for SBP; moderate for DBP, HDL, TRIG and TC/HDL; and lowest for LDL and TC. Of the anthropometric variables, WC demonstrated the greatest correlations with the risk variables. The first canonical correlations were significant (p < 0.0001) in men (0.58) and women (0.61) of all ages. Of the anthropometric variables, WC consistently demonstrated the highest loading values in the first canonical variable in men (0.56) and women (0.59). Of the risk variables in both sexes, the loadings of TRIG were generally the largest, those of HDL, SBP, DBP intermediate and those of LDL the smallest. In men, the strength of these associations generally decreased with age, whereas in women they peaked in the 35-54 year age group. Conclusion: Considerable association was seen between measures of abdominal obesity and blood pressure and plasma lipid levels. WC is the measure of abdominal obesity most highly correlated with these cardiovascular disease risk factors.
Objectives: To provide Canadian physicians with a standard definition of hypertension in pregnanc... more Objectives: To provide Canadian physicians with a standard definition of hypertension in pregnancy, recommendations for laboratory investigations and tests for the assessment and management of hypertensive disorders in pregnancy, and a classification of such disorders. Options: To improve or not improve Canadian uniformity and standardization in the investigation and classification of hypertensive disorders in pregnancy. Outcomes: 1) Accuracy, reliability and practicality of diagnostic clinical criteria for hypertensive disorders in pregnancy. 2) Laboratory tests useful to determine severity and prognosis of disorders as measured by maternal and neonatal adverse outcomes. 3) A classification of disorders for use by Canadian physicians to facilitate uniformity and diffusion of research through a common language. Evidence: Articles on hypertensive disorders in pregnancy published from 1966 to 1996, retrieved through MEDLINE search, related to definitions, tests, diagnostic criteria and classification, as well as documents on diagnosis and classification from authorities in the United States, Europe and Australia and from special interest groups. Values: High priority was given to the principle of preventing adverse maternal and neonatal outcomes through the provision of diagnostic criteria for severity and prognosis and through dissemination of reliable and pertinent information and research results using a common language. BENEFITS, HARMS AND COST: Higher degree of vigilance in diagnosing hypertensive disorders in pregnancy, allowing for earlier assessment and intervention, and more efficient dissemination of comparative information through common language. No harm or added cost is perceived at this time. Recommendations: (1) A diastolic blood pressure of 90 mm Hg or more should be the criterion for a diagnosis of hypertension in pregnancy and should trigger investigation and management. Except for very high diastolic readings (110 mm Hg or more), all diastolic readings of 90 mm Hg or more should be confirmed after 4 hours. (2) A regularly calibrated mercury sphygmomanometer, with an appropriate-sized cuff, is the instrument of choice. A rest period of 10 minutes should be allowed before taking the blood pressure. The woman should be sitting upright and the cuff positioned at the level of the heart. (3) Both Korotkoff phase IV and V sounds should be recorded, but the phase IV sound should be used for initiating clinical investigation and management. (4) A urine protein level of more than 0.3 g/d should be the criterion for a diagnosis of proteinuria; 24-hour urine collection should be the standard method for determining proteinuria. (5) Edema and weight gain should not be used as diagnostic criteria. (6) Hypertensive disorders diagnosed during pregnancy should be classified as pre-existing hypertension; gestational hypertension with or without proteinuria; pre-existing hypertension with superimposed gestational hypertension with proteinuria; and unclassifiable antenatally but final classification 42 days after delivery. Validation: Except for expert opinions and reviews solicited for this project, these recommendations need to be field tested and validated in Canada. Guidelines endorsed by the Canadian Hypertension Society and the Society of Obstetricians and Gynaecologists of Canada.
OBJECTIVE Heart failure with preserved ejection (HFpEF) represents nearly half of all patients wi... more OBJECTIVE Heart failure with preserved ejection (HFpEF) represents nearly half of all patients with heart failure (HF). The objective of this study was to determine whether patient characteristics identify discrete kinds of HFpEF. METHODS Data were collected on 196 patients with HFpEF in a non-hospitalized setting. Clinical and laboratory variables were collected, and 47 candidate variables were examined by the unsupervised clustering strategy partitioning around medoids. The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was calculated. Follow-up data on all-cause mortality, cardiovascular mortality, and HF exacerbation, were collected and were not part of the data used to identify subgroups. RESULTS Six significantly different groups or clusters were found. There were three groups of women (i) individuals with a low proportion of vascular risk factors (HFpEF1) (ii) individuals with a high proportion of hypertension and diabetes, but lower proportion of kidney disease and diastolic dysfunction (HFpEF3) (iii) older individuals with high rates of atrial fibrillation (AF), chronic kidney disease. They had the worst long-term outcomes (HFpEF4). There were three groups of men (i) individuals with a high proportion of coronary artery disease (CAD), dyslipidemia, higher serum creatinine, and diastolic dysfunction (HFpEF2) (ii) individuals with highest BMI, and high proportion of CAD, obstructive sleep apnea, and poorly controlled diabetes (HFpEF5) (iii) individuals with high rates of AF, elevated BNP, biventricular remodeling (HFpEF6). They had a high cardiovascular mortality. CONCLUSIONS HFpEF consists of a heterogenous group of individuals with six distinct clinical subsets that have different long-term outcomes.
In 812 patients who underwent routine preoperative electrocardiography a mean of 24.6 months afte... more In 812 patients who underwent routine preoperative electrocardiography a mean of 24.6 months after undergoing electrocardiography at the same institution, the frequency of new abnormalities was estimated to evaluate the cost-effectiveness of this procedure prior to an operation. New abnormalities were judged to be either relevant or irrelevant to the assessment of operative risk, depending upon their previously demonstrated correlation with operative and postoperative morbidity and mortality. Since new abnormalities, especially new relevant abnormalities, were found to be relatively infrequent, the cost-effectiveness of routine preoperative electrocardiography was considered to be low. The evidence suggested that when a previous tracing exists preoperative electrocardiography is most clearly indicated for patients who are 60 years of age or older or whose previous tracing exhibited abnormalities. However, further research is required to develop more sensitive and specific protocols, and to evaluate the role of repeat electrocardiography in clinical decision-making.
Background and Objective: Palpitations are a common symptom that may indicate cardiac arrhythmias... more Background and Objective: Palpitations are a common symptom that may indicate cardiac arrhythmias, be a somatic complaint in anxiety disorders, and can be present in patients without either condition. The objective of this review was to explore the pathways and fundamental mechanisms through which individuals appreciate palpitations. Observations: Cardiac afferents provide beat-to-beat sensory information on the heart to the spinal cord, brain stem, and higher brain centers. Cardioception, a subset of interoception (‘the physiological sense of the condition of the body’), refers to sensing of the heartbeat. High cardioception is present in persons with lower body mass index, lower percentages of body fat, and anxiety disorders. Low cardioception (lower interoceptive awareness) is associated with psychiatric disorders, such as depression, personality disorders, and schizophrenia. CNS sites associated with heartbeat detection have been identified by functional magnetic resonance imaging studies and heartbeat-evoked electroencephalogram potentials. The right insula, cingulate gyrus, somatomotor and somatosensory cortices nucleus accumbens, left subthalamic nucleus, and left ventral capsule/striatum are implicated in both palpitations and heartbeat detection. Involvement of the brain as a primary modulator of palpitations rests on the data that various areas of the brain are activated in association with cardioception, the ability of focal brain stimulation to induce palpitations, the ability of central alpha receptor agonists and antagonists to modulate palpitations, and suppression of palpitations by transcranial repetitive magnetic stimulation (rTMS). Conclusions: Palpitations should be viewed as a pathway extending from the heart to the brain. Palpitations are, in part, a reflection of an individual’s cardioception awareness, which is modulated by body size, percentage of body fat, and psychological or psychiatric conditions. Palpitations can originate in the brain and involve central neurotransmitters. Treatment of palpitations unrelated to cardiac arrhythmias or anxiety disorders should consider the use of central alpha-2 agonists and possibly rTMS.
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Papers by Simon Rabkin