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1.  Atrioventricular Heart Block and Syncope Coincident With Diagnosis of Systemic Lupus Erythematosus 
The Canadian journal of cardiology  2013;29(10):1330.e5-1330.e7.
We describe a 59-year-old woman with cardiac conduction abnormalities caused by lupus-induced myocardial damage. She had a history of arthralgias and antinuclear antibodies but no clinical history of systemic lupus erythematosus. She presented with syncope and Mobitz type II second-degree atrioventricular block. Anti-double-stranded DNA antibodies developed coincident with the identification of heart block. Cardiac magnetic resonance imaging showed late enhancing foci of gadolinium uptake that anatomically correlated with her conduction abnormalities. We conclude that her conduction disease represents an early and structural cardiac manifestation of systemic lupus erythematosus that is unusual in its presentation at the time of initial diagnosis.
PMCID: PMC3904292  PMID: 23916739
2.  Targeted Ablation at Stable Atrial Fibrillation Sources Improves Success Over Conventional Ablation In High Risk Patients A Substudy of the CONFIRM Trial 
The Canadian journal of cardiology  2013;29(10):1218-1226.
Pulmonary vein (PV) isolation has disappointing results in patients with obesity, heart failure, obstructive sleep apnea (OSA) and enlarged left atria (LA), for unclear reasons. We hypothesized that these comorbidities cause higher numbers or non-PV locations of AF sources, where targeted source ablation (Focal Impulse and Rotor Modulation, FIRM) should improve the single-procedure success of ablation.
The CONFIRM trial prospectively enrolled 92 patients at 107 AF ablation procedures, in whom computational mapping identified AF rotors or focal sources. Patients underwent FIRM plus conventional ablation (FIRM-guided), or conventional ablation only, and were evaluated for recurrent AF quarterly with rigorous, often implanted, monitoring. We report the n=73 patients undergoing first ablation in whom demographic information was available (n= 52 conventional, n=21 FIRM-guided).
Stable sources for AF were found in 97.1% of patients. The numbers of concurrent sources per patient (2.1±1.1) rose with LA diameter (p=0.021), lower LV ejection fraction (p=0.039), and the presence of obstructive sleep apnea (OSA, p=0.002) or hypomagnesemia (p=0.017). Right atrial sources were associated with obesity (BMI≥30 kg/m2, p=0.015). In patients with obesity, hypertension, OSA and LA diameter > 40 mm, single-procedure freedom from AF was >80% by FIRM-guided versus <50% by conventional ablation (all; p<0.05).
Patients with ‘difficult to treat’ AF exhibit more concurrent AF sources in more widespread biatrial distributions than other patients. These mechanisms explain the disappointing results of PV isolation, and how FIRM can identify patient-specific AF sources to enable successful ablation in this population.
PMCID: PMC3787988  PMID: 23993247
Atrium; Fibrillation; Rotors; FIRM ablation; Metabolic syndrome; Sleep apnea; Clinical Trials
3.  Echocardiography Underestimates Stroke Volume and Aortic Valve Area: Implications for Patients With Small-Area Low-Gradient Aortic Stenosis 
The Canadian Journal of Cardiology  2014;30(9):1064-1072.
Discordance between small aortic valve area (AVA; < 1.0 cm2) and low mean pressure gradient (MPG; < 40 mm Hg) affects a third of patients with moderate or severe aortic stenosis (AS). We hypothesized that this is largely due to inaccurate echocardiographic measurements of the left ventricular outflow tract area (LVOTarea) and stroke volume alongside inconsistencies in recommended thresholds.
One hundred thirty-three patients with mild to severe AS and 33 control individuals underwent comprehensive echocardiography and cardiovascular magnetic resonance imaging (MRI). Stroke volume and LVOTarea were calculated using echocardiography and MRI, and the effects on AVA estimation were assessed. The relationship between AVA and MPG measurements was then modelled with nonlinear regression and consistent thresholds for these parameters calculated. Finally the effect of these modified AVA measurements and novel thresholds on the number of patients with small-area low-gradient AS was investigated.
Compared with MRI, echocardiography underestimated LVOTarea (n = 40; −0.7 cm2; 95% confidence interval [CI], −2.6 to 1.3), stroke volumes (−6.5 mL/m2; 95% CI, −28.9 to 16.0) and consequently, AVA (−0.23 cm2; 95% CI, −1.01 to 0.59). Moreover, an AVA of 1.0 cm2 corresponded to MPG of 24 mm Hg based on echocardiographic measurements and 37 mm Hg after correction with MRI-derived stroke volumes. Based on conventional measures, 56 patients had discordant small-area low-gradient AS. Using MRI-derived stroke volumes and the revised thresholds, a 48% reduction in discordance was observed (n = 29).
Echocardiography underestimated LVOTarea, stroke volume, and therefore AVA, compared with MRI. The thresholds based on current guidelines were also inconsistent. In combination, these factors explain > 40% of patients with discordant small-area low-gradient AS.
PMCID: PMC4161727  PMID: 25151288
4.  Cardiovascular Pharmacogenomics: The Future of Cardiovascular Therapeutics? 
Responses to drug therapy vary from benefit to no effect to adverse effects which can be serious or occasionally fatal. Increasing evidence supports the idea that genetic variants can play a major role in this spectrum of responses. Well-studied examples in cardiovascular therapeutics include predictors of steady-state warfarin dosage, predictors of reduced efficacy among patients receiving clopidogrel for drug eluting stents, and predictors of some serious adverse drug effects. This review summarizes contemporary approaches to identifying and validating genetic predictors of variability in response to drug treatment. Approaches to incorporating this new knowledge into clinical care, and the barriers to this concept, are addressed.
PMCID: PMC3529768  PMID: 23200096
5.  Bucindolol, systolic blood pressure, and outcomes in systolic heart failure: a prespecified post hoc analysis of BEST 
In the Beta-Blocker Evaluation of Survival Trial (BEST) trial, systolic blood pressure (SBP) ≤120 mm Hg was an independent predictor of poor prognosis in ambulatory patients with chronic systolic heart failure (HF). Because SBP is an important predictor of response to beta-blocker therapy, the BEST protocol had pre-specified a post hoc analysis to determine if the effect of bucindolol varied by baseline SBP.
In the BEST, 2706 patients with chronic systolic (left ventricular ejection fraction <35%) HF and New York Heart Association class III (92%) or IV (8%) symptoms and receiving standard background therapy were randomized to receive either bucindolol (n=1354) or placebo (n=1354). Of these, 1751 had SBP ≤120 mm Hg and 955 had SBP >120 mm Hg at baseline.
Among patients with SBP >120 mm Hg, all-cause mortality occurred in 28% and 22% of patients receiving placebo and bucindolol, respectively (hazard ratio when bucindolol was compared with placebo, 0.77; 95% confidence interval, 0.59–0.99; P=0.039). In contrast, among those with SBP ≤120 mm Hg, 36% and 35% of patients in the placebo and bucindolol groups died, respectively (hazard ratio, 0.95; 95% confidence interval, 0.81–1.12; P=0.541). Hazard ratios (95% confidence intervals) for HF hospitalization associated with bucindolol use were 0.70 (0.56–0.89; P=0.003) and 0.82 (0.71–0.95; P=0.008) for patients with SBP >120 and ≤120 mm Hg, respectively.
Bucindolol, a nonselective beta-blocker with weak alpha-blocking properties, significantly reduced HF hospitalization in systolic HF patients regardless of baseline SBP. However, bucindolol reduced mortality only in those with SBP >120 mm Hg.
PMCID: PMC3769783  PMID: 21982425
Bucindolol; systolic blood pressure; outcomes; heart failure
6.  There Is Power in Numbers—Even/Especially in Genomic Medicine 
PMCID: PMC3674099  PMID: 22326711
7.  Pulmonary Endarterectomy Surgery- A Technically Demanding Cure for WHO Group IV Pulmonary Hypertension: Requirements for Centers of Excellence and Availability in Canada 
PMCID: PMC3555483  PMID: 22019277
chronic thromboembolic pulmonary hypertension (CTEPH); pulmonary embolism; registries; pulmonary vascular resistance; pulmonary hypertension
10.  A farewell to my first-born journal 
PMCID: PMC3006095  PMID: 21165356
11.  A Changing World 
PMCID: PMC3006096  PMID: 21165358
14.  Two novel mutations of the MYBPC3 gene identified in Chinese families with hypertrophic cardiomyopathy 
The Canadian Journal of Cardiology  2010;26(10):518-522.
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular disorders. Mutations in the MYBPC3 gene are one of the most frequent genetic causes of HCM.
To screen MYBPC3 gene mutations in Chinese patients with HCM, and analyze the correlation between the genotype and the phenotype.
The 35 exons of the MYBPC3 gene were amplified by polymerase chain reaction in the 11 consecutive unrelated Chinese pedigrees. The sequences of the products were analyzed and the mutation sites were determined. The clinical data of genotype-positive families were collected, and the correlation between genotype and phenotype was analyzed.
Two mutations of the MYBPC3 gene were confirmed among 11 pedigrees. A frameshift mutation (Pro459fs) was identified in exon 17 in family H8, and a splice mutation (IVS5+5G→C) was identified in intron 5 in family H3. These two mutations were first identified in Chinese patients with familial HCM and were absent in 110 chromosomes of healthy controls. Seven known polymorphisms were found in the cohort.
Compared with what was reported abroad, the MYBPC3 gene is a common pathogenic gene responsible for HCM in Chinese patients, and the phenotypes of these two mutations in their respective families may have their own clinical characteristics.
PMCID: PMC3006099  PMID: 21165360
Familial hypertrophic cardiomyopathy; Genotype; Mutation; MYBPC3; Phenotype
15.  Trends in postacute myocardial infarction management and mortality in patients with diabetes. A population-based study from 1995 to 2001 
The Canadian Journal of Cardiology  2010;26(10):523-531.
To compare trends in coronary revascularization use and case fatality rate (CFR) following acute myocardial infarction in patients with and without diabetes.
A retrospective study of 77,552 patients, 20 years of age or older (25% with diabetes), who were hospitalized for a first acute myocardial infarction in the province of Quebec between April 1995 and December 2001 was conducted. Administrative databases were used to identify patients and assess outcomes.
Compared with patients without diabetes, patients with diabetes underwent more coronary artery bypass graft (CABG) surgeries (11.1% versus 8.3%; P<0.0001) but fewer percutaneous coronary interventions (17.1% versus 20.2%; P<0.0001). The use of percutaneous coronary intervention increased substantially over time in both populations, driven mainly by an increase during the index admission (20.6% versus 16.6% per year; P=0.1144 in patients with and without diabetes, respectively). The use of CABG during the index admission increased markedly among patients with diabetes compared with those without (10.3% versus 5.3% per year; P=0.0072); however, at one-year following discharge, CABG use remained stable in patients with diabetes and fell in those without (−0.7% versus −5.3% per year; P=0.2046). Concomitantly, patients with diabetes presented a similar decline in CFR compared with patients without diabetes. The decline was more pronounced during the index admission (−5.0% versus −4.1% per year; P=0.282) than at one-year following discharge (−2.5% versus −2.5% per year; P=0.629) in patients with and without diabetes, respectively. However, fatal outcome remained higher in patients with diabetes than without, with an adjusted RR of 1.21 (95% CI 1.18 to 1.24) at one-year follow-up.
Overall, coronary revascularization use and CFR improved over time in patients with diabetes. Nevertheless, the mortality rate in patients with diabetes remains higher than in patients without diabetes, indicating that additional progress is required to improve the poorer prognosis in this population.
PMCID: PMC3006100  PMID: 21165361
Acute myocardial infarction; Diabetes mellitus; Mortality; Revascularization
16.  Patient-prosthesis mismatch in the mitral position affects midterm survival and functional status 
The Canadian Journal of Cardiology  2010;26(10):532-536.
The definition and incidence of patient-prosthesis mismatch (PPM) in the mitral position are unclear.
To determine the impact of PPM on late survival and functional status after mitral valve replacement with a mechanical valve.
Between 1992 and 2005, 714 patients (mean [± SD] age 60±10 years) underwent valve replacement with either St Jude (St Jude Medical Inc, USA) (n=295) or Carbomedics (Sulzer Carbomedics Inc, USA) (n=419) valves. There were 52 concomitant procedures (50 tricuspid annuloplasties, 25 foramen oval closures and 20 radiofrequency mazes). The mean clinical follow-up period was 4.4±3.3 years. The severity of PPM was established with cut-off values for an indexed effective orifice area (EOAi) of lower than 1.2 cm2/m2, lower than 1.3 cm2/m2 and lower than 1.4 cm2/m2. Parametric and nonparametric tests were used to determine predictors of outcome.
The prevalence of PPM was 3.7%, 10.1% and 23.5% when considering values of lower than 1.2 cm2/m2, lower than 1.3 cm2/m2 and lower than 1.4 cm2/m2, respectively. When considering functional improvement, patients with an EOAi of 1.4 cm2/m2 or greater had a better outcome than those with an EOAi of lower than 1.4 cm2/m2 (OR 1.98; P=0.03). When building a Cox-proportional hazard model, PPM with an EOAi of less than 1.3 cm2/m2 was an independent predictive factor for midterm survival (HR 2.24, P=0.007). Other factors affecting survival were age (HR 1.039), preoperative New York Heart Association class (HR 1.96) and body surface area (HR 0.31).
In a large cohort of patients undergoing mitral valve replacement with mechanical prostheses, PPM defined as an EOAi of lower than 1.3 cm2/m2 significantly decreased midterm survival. This level of PPM was observed in 10.2% of patients. Patients with an EOAi of 1.4 cm2/m2 or greater had greater improvement of their functional status.
PMCID: PMC3006101  PMID: 21165362
Mitral valve; Prosthesis; Surgery; Valvuloplasty
17.  Knowledge of heart disease and stroke among cardiology inpatients and outpatients in a Canadian inner-city urban hospital 
The Canadian Journal of Cardiology  2010;26(10):537-541.
Heart disease and stroke are leading causes of death in North America. Nevertheless, in 2003, the Heart and Stroke Foundation of Canada reported that nearly two-thirds of Canadians have misconceptions regarding heart disease and stroke, echoing the results of similar American studies. Good knowledge of these conditions is imperative for cardiac patients who are at greater risk than the general population and should, therefore, be better educated. The present study evaluated the awareness of heart disease and stroke among cardiac patients to assess the efficacy of current education efforts.
Two hundred fifty-one cardiac inpatients and outpatients at St Michael’s Hospital (Toronto, Ontario) were surveyed in July and August 2004. An unaided questionnaire assessed respondents’ knowledge of cardiovascular risk factors, symptoms of heart attack and stroke, and actions in the event of cardiovascular emergency. Demographic data and relevant medical history were also obtained.
Cardiac patients demonstrated relatively adequate knowledge of heart attack warning symptoms. These patients also demonstrated adequate awareness of proper actions during cardiovascular emergencies. However, respondents were not aware of the most important risk factors for cardiovascular disease. Knowledge of stroke symptoms was also extremely poor. Socioeconomic status, and personal history of heart attack and stroke were positively correlated with good knowledge.
Future patient education efforts should address the awareness of the important cardiovascular risk factors and knowledge of cardiovascular warning symptoms (especially for stroke), as well as inform patients of appropriate actions during a cardiovascular emergency. Emphasis should be placed on primary and secondary prevention, and interventions should be directed toward low-income cardiac patients.
PMCID: PMC3006102  PMID: 21165363
Heart attack; Myocardial infarction; Prevention; Public health education; Stroke
18.  Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system? 
The Canadian Journal of Cardiology  2010;26(10):542-548.
Dyslipidemia results from consumption of a diet rich in saturated fatty acids and is usually associated with cardiovascular disease. A diet rich in unsaturated fatty acids is usually associated with improved cardiovascular condition.
To investigate whether a high-fat diet rich in unsaturated fatty acids (U-HFD) – in which fatty acid represents approximately 45% of the total calories – impairs the cardiovascular system.
Male, 30-day-old Wistar rats were fed a standard (control) diet or a U-HFD containing 83% unsaturated fatty acid for 19 weeks. The in vivo electrocardiogram, the spectral analysis of heart rate variability, and the vascular reactivity responses to phenylephrine, acetylcholine, noradrenaline and prazosin in aortic ring preparations were analyzed to assess the cardiovascular parameters.
After 19 weeks, the U-HFD rats had increased total body fat, baseline glucose levels and feed efficiency compared with control rats. However, the final body weight, systolic blood pressure, area under the curve for glucose, calorie intake and heart weight/final body weight ratio were similar between the groups. In addition, both groups demonstrated no alteration in the electrocardiogram or cardiac sympathetic parameters. There was no difference in the responses to acetylcholine or the maximal contractile response of the thoracic aorta to phenylephrine between groups, but the concentration necessary to produce 50% of maximal response showed a decrease in the sensitivity to phenylephrine in U-HFD rats. The cumulative concentration-effect curve for noradrenaline in the presence of prazosin was shifted similarly in both groups.
The present work shows that U-HFD did not impair the cardiovascular parameters analyzed.
PMCID: PMC3006103  PMID: 21165364
Cardiovascular; High-fat diet; Obesity; Unsaturated fatty acid
19.  Recurrent myopericarditis with extensive ulcerative colitis 
The Canadian Journal of Cardiology  2010;26(10):549-550.
A 26-year-old man with ulcerative colitis was independently evaluated in different emergency rooms on two occasions, separated by six years, for episodes of severe chest pain consistent with myopericarditis. Cardiac enzyme and electrocardiographic changes were accompanied by extensive colonic inflammatory changes. Treatment with corticosteroids led to resolution. While his cardiac findings were initially believed to be caused by a previously reported drug hypersensitivity to mesalamine (5-aminosalicylate), sulphasalazine was tolerated. Recurrent myopericarditis with ulcerative colitis appears to be rare, but responsive to steroids. It may occur more often than is currently appreciated and may lead to fatal arrhythmias or cardiac failure.
PMCID: PMC3006104  PMID: 21165365
5-Aminosalicylates; Inflammatory bowel disease; Myocarditis; Pericarditis; Ulcerative colitis
20.  The accuracy of the physical examination for the detection of lower extremity peripheral arterial disease 
The Canadian Journal of Cardiology  2010;26(10):e346-e350.
Peripheral arterial disease (PAD) is a major risk factor for adverse cardiovascular events. There has been a definite push for wider use of the ankle-brachial index (ABI) as a simple screening tool for PAD. Perhaps this has occurred to the detriment of a thorough physical examination.
To assess the accuracy of the physical examination to detect clinically significant PAD compared with the ABI.
PADfile, the PAD module of CARDIOfile (the Kingston Heart Clinic’s cardiology database [Kingston, Ontario]), was searched for all patients who underwent peripheral arterial testing. Of 1619 patients, 1236 had all of the necessary data entered. Patients’ lower limbs were divided into two groups: those with a normal ABI between 0.91 and 1.30, and those with an abnormal ABI of 0.90 or lower. Peripheral pulses were graded as either absent or present. Absent was graded as 0/3, present but reduced (1/3), normal (2/3) or bounding (3/3). Femoral bruits were graded as either present (1) or absent (0). Using the ABI as the gold standard, the sensitivity, specificity, negative predictive value (NPV), positive predictive value and overall accuracy were calculated for the dorsalis pedis pulse, the posterior tibial pulse, both pedal pulses, the presence or absence of a femoral bruit and, finally, for a combination of both pedal pulses and the presence or absence of a femoral bruit.
In 1236 patients who underwent PAD testing and who underwent a complete peripheral vascular physical examination (all dorsalis pedis and posterior tibial pulses palpated and auscultation for a femoral bruit), the sensitivity, specificity, NPV, positive predictive value and accuracy for PAD were 58.2%, 98.3%, 94.9%, 81.1% and 93.8%, respectively.
The clinical examination of the peripheral arterial foot pulses and the auscultation for a femoral bruit had a high degree of accuracy (93.8%) for the detection or exclusion of PAD compared with the ABI using the cut-off of 0.90 or lower. If both peripheral foot pulses are present in both lower limbs and there are no femoral bruits, the specificity and NPV of 98.3% and 94.9%, respectively, make the measurement of the ABI seem redundant. The emphasis in PAD detection should be redirected toward encouraging a thorough physical examination.
PMCID: PMC3006105  PMID: 21165366
Ankle-brachial index; Peripheral arterial disease; Physical examination
21.  Toxic shock syndrome: A rare complication to enhanced external counterpulsation 
The Canadian Journal of Cardiology  2010;26(10):e351-e352.
Enhanced external counterpulsation (EECP) is known to reduce angina pectoris in patients in whom revascularization is not possible. The therapy is associated with few adverse effects. A case with a previously unknown complication – toxic shock syndrome – that occurred twice in an EECP-treated patient is described. Toxic shock syndrome initially resembles the state of septic shock. Early recognition of the syndrome and initiation of therapy is of vital importance to prevent rapid progression and a possibly fatal outcome. Awareness of this condition among cardiologists offering EECP is essential.
PMCID: PMC3006106  PMID: 21165367
EEC; Enhanced external counterpulsation; Toxic shock syndrome; TSS
22.  Echocardiographic tools for pacemaker optimization of ventricular function in an infant following surgical repair for double outlet right ventricle 
The Canadian Journal of Cardiology  2010;26(10):e353-e355.
A case of an infant, following surgical repair for double outlet right ventricle, who developed low cardiac output syndrome and complete heart block that required insertion of a pacemaker is presented. The infant underwent optimization of his ventricular function to determine whether pacing the right ventricle or left ventricle or both would improve cardiac function. Using standard two-dimensional echocardiography and Doppler imaging, tissue synchronization imaging, and two-dimensional speckle-tracking strain analysis, improvement in cardiac output and function was demonstrated. The present case highlights the usefulness of newer echocardiographic techniques in pacemaker optimization in the acute postoperative setting.
PMCID: PMC3006107  PMID: 21165368
Congenital heart disease; Tissue and strain Doppler echocardiography
25.  Daily low-dose folic acid supplementation does not prevent nitroglycerin-induced nitric oxide synthase dysfunction and tolerance: A human in vivo study 
Continuous treatment with nitroglycerin (GTN) causes tolerance and endothelial dysfunction, both of which may involve endothelial nitric oxide synthase (eNOS) dysfunction. eNOS dysfunction may be linked to depletion of tetrahydrobiopterin, and folic acid may be involved in the regeneration of this cofactor. It has been demonstrated that 10 mg/day folic acid supplementation prevents the development of GTN tolerance and GTN-induced endothelial dysfunction. However, the efficacy of daily lower-dose folic acid supplementation for preventing these phenomena has not been investigated.
To determine the effect of 1 mg/day folic acid supplementation on responses to sustained GTN therapy.
On visit 1, 20 healthy male volunteers were randomly assigned to receive either oral folic acid (1 mg/day) or placebo for one week in a double- blind study. All subjects also received continuous transdermal GTN (0.6 mg/h). On visit 2, forearm blood flow was measured using venous occlusion strain-gauge plethysmography in response to incremental intra-arterial infusions of acetylcholine, N-monomethyl-L-arginine and GTN. Subjects in both groups displayed significantly decreased responses to acetylcholine and N-monomethyl-L-arginine infusions compared with a control group that received no treatment. Responses to GTN were also significantly diminished in both groups (P<0.05 for all).
The present data demonstrate that daily supplementation with 1 mg folic acid does not prevent the development of GTN-induced eNOS dysfunction or tolerance.
PMCID: PMC2989350  PMID: 21076717
Acetylcholine; Blood flow; Endothelial dysfunction; Folic acid; Nitric oxide synthase; Nitroglycerin; Superoxide

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