Ashwat Dhillon

Cardiac magnetic resonance in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is a complex genetic cardiovascular disorder with substantial variability in phenotypic expression and natural progression. Recent research demonstrates the incremental utility of cardiac magnetic resonance in the diagnosis, therapeutic planning, and prognostication of this disease. The increasing incorporation of multimodality imaging of hypertrophic cardiomyopathy in clinical practice will continue to improve our understanding of the subtle morphologic differences and their prognostic implications.

Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy Patients Without Severe Septal Hypertrophy Implications of Mitral Valve and Papillary Muscle Abnormalities Assessed Using Cardiac Magnetic Resonance and Echocardiography

Background—In patients with hypertrophic cardiomyopathy and left ventricular outflow tract (LVOT) obstruction, but without basal septal hypertrophy, we sought to identify mitral valve (MV) and papillary muscle (PM) abnormalities that predisposed to LVOT obstruction, using echo and cardiac magnetic resonance. Methods and Results—We studied 121 patients with hypertrophic cardiomyopathy hypertrophic cardiomyopathy (age, 49±17 years; 60% men; 57% on &bgr;-blockers) with a basal septal thickness of ⩽1.8 cm who underwent echocardiography (rest+stress) and cine cardiac magnetic resonance. Echo measurements included maximal LVOT gradient (rest/provocable), MV leaflet length (parasternal long, 4 and 3-chamber views), and abnormal chordal attachment to mid/base of anterior MV. Cine cardiac magnetic resonance measurements included basal septal thickness, number/area of PM heads, and bifid PM mobility (in systole and diastole). Mean basal septal thickness, LVOT gradient, and LV ejection fraction were 1.5±0.3 cm, 72±54 mm Hg, and 61±6%, respectively. The number of anterolateral and posteromedial PM heads was 2.7±0.7 and 2.6±0.7, respectively. Anterolateral and posteromedial PM areas were 19.9±7 cm2 and 17.1±6 cm2, respectively. PM mobility was 11±6°. On multivariable analysis, predictors of maximal LVOT gradient were basal septal thickness, bifid PM mobility, anterior mitral leaflet length, and abnormal chordal attachment to base of anterior mitral leaflet. Forty-five patients underwent surgery to relieve LVOT obstruction, of which 52% needed an additional nonmyectomy (MV repair/replacement or PM reorientation) approach. Conclusions—In hypertrophic cardiomyopathy patients without significant LV hypertrophy, in addition to basal septal thickness, anterior MV length, abnormal chordal attachment, and bifid PM mobility are associated with LVOT obstruction. In such patients, additional procedures on MV and PM (±myectomy) could be considered.Background— In patients with hypertrophic cardiomyopathy and left ventricular outflow tract (LVOT) obstruction, but without basal septal hypertrophy, we sought to identify mitral valve (MV) and papillary muscle (PM) abnormalities that predisposed to LVOT obstruction, using echo and cardiac magnetic resonance. Methods and Results— We studied 121 patients with hypertrophic cardiomyopathy hypertrophic cardiomyopathy (age, 49±17 years; 60% men; 57% on β-blockers) with a basal septal thickness of ≤1.8 cm who underwent echocardiography (rest+stress) and cine cardiac magnetic resonance. Echo measurements included maximal LVOT gradient (rest/provocable), MV leaflet length (parasternal long, 4 and 3-chamber views), and abnormal chordal attachment to mid/base of anterior MV. Cine cardiac magnetic resonance measurements included basal septal thickness, number/area of PM heads, and bifid PM mobility (in systole and diastole). Mean basal septal thickness, LVOT gradient, and LV ejection fraction were 1.5±0.3 cm, 72±54 mm Hg, and 61±6%, respectively. The number of anterolateral and posteromedial PM heads was 2.7±0.7 and 2.6±0.7, respectively. Anterolateral and posteromedial PM areas were 19.9±7 cm2 and 17.1±6 cm2, respectively. PM mobility was 11±6°. On multivariable analysis, predictors of maximal LVOT gradient were basal septal thickness, bifid PM mobility, anterior mitral leaflet length, and abnormal chordal attachment to base of anterior mitral leaflet. Forty-five patients underwent surgery to relieve LVOT obstruction, of which 52% needed an additional nonmyectomy (MV repair/replacement or PM reorientation) approach. Conclusions— In hypertrophic cardiomyopathy patients without significant LV hypertrophy, in addition to basal septal thickness, anterior MV length, abnormal chordal attachment, and bifid PM mobility are associated with LVOT obstruction. In such patients, additional procedures on MV and PM (±myectomy) could be considered.

Diagnostic Utility of Cardiac Biomarkers in Discriminating Takotsubo Cardiomyopathy From Acute Myocardial Infarction

BACKGROUND Takotsubo cardiomyopathy (TC) mimics acute myocardial infarction (AMI). We postulated that ventricular dysfunction in TC in the absence of significant myocardial necrosis would produce higher B-type natriuretic peptide (BNP)/troponin T (TnT) and BNP/creatine kinase MB fraction (CKMB) ratios than in AMI. METHODS AND RESULTS We studied 58 consecutive TC (age 65.8 ± 82.9) and 97 AMI patients (age 59.8 ± 83.4). The ratios of BNP/TnT and BNP/CKMB were calculated with the use of first simultaneously drawn laboratory values. Receiver operating characteristic curves were used to distinguish TC from AMI with 95% specificity based on cardiac biomarker ratios. Median BNP/TnT and BNP/CKMB ratios were, respectively, 1,292 [interquartile range 443.4-2,657.9] and 28.44 [13.7-94.8] in the TC group and 226.9 [69.91-426.32] and 3.63 [1.07-10.02] in the AMI group (P < .001). TC can be distinguished from AMI with 95% specificity with the use of BNP/TnT ratio ≥ 1,272 (sensitivity 52%) and BNP/CKMB ratio ≥ 29.9 (sensitivity 50%). CONCLUSIONS The value of BNP is significantly higher in TC than in AMI. Early BNP/TnT and BNP/CKMB ratios help to differentiate TC from AMI with greater accuracy than BNP alone.

Association of Noninvasively Measured Left Ventricular Mechanics With In Vitro Muscle Contractile Performance: A Prospective Study in Hypertrophic Cardiomyopathy Patients

BACKGROUND Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in which regional left ventricular dysfunction may exist without overt global left ventricular dysfunction. In obstructive HCM patients who underwent surgical myectomy (SM), we sought to determine if there is a significant association between echocardiographic longitudinal strain, histopathology, and in vitro myocardial performance (resting tension and developed tension) of the surgical specimen. METHODS AND RESULTS HCM patients (n=122, 54±14 years, 54% men) undergoing SM were prospectively recruited. Longitudinal systolic strain and diastolic strain rates were measured at that basal septum (partially removed at SM) by using velocity vector imaging on preoperative echocardiography. Semiquantitative histopathologic grading of myocyte disarray and fibrosis and in vitro measurements of resting tension and developed tension were made in septal tissue obtained at SM. Mean basal septal systolic strain and diastolic strain rate were -8.3±5% and 0.62±0.4/s, while mild or greater degree of myocyte disarray and interstitial fibrosis were present in 85% and 87%, respectively. Mean resting tension and developed tension were 2.8±1 and 1.4±0.8 g/mm(2). On regression analysis, basal septal systolic strain, diastolic strain rate, disarray, and fibrosis were associated with developed tension (β=0.19, 0.20, -0.33, and -0.40, respectively, all P<0.01) and resting tension (β=0.21, 0.22, -0.25, and -0.28, respectively, all P<0.01). CONCLUSION In obstructive HCM patients who underwent SM, left ventricular mechanics (echocardiographic longitudinal systolic strain and diastolic strain rates), assessed at the basal septum (myocardium removed during myectomy) and histopathologic findings characteristic for HCM (disarray and fibrosis) were significantly associated with in vitro myocardial resting and developed contractile performance.

Differences in global and regional left ventricular myocardial mechanics in various morphologic subtypes of patients with obstructive hypertrophic cardiomyopathy referred for ventricular septal myotomy/myectomy.

Patients with obstructive hypertrophic cardiomyopathy (HC) have various left ventricular (LV) shapes: reverse septal curvature (RSC, commonly familial), sigmoid septum (SS, common in hypertensives), and concentric hypertrophy (CH). Longitudinal (systolic and early diastolic) strain rate (SR) is sensitive in detecting regional myocardial dysfunction. We sought to determine differences in longitudinal SR of patients with obstructive HC, based on LV shapes. We studied 199 consecutive patients with HC (50% men) referred for surgical myectomy. Clinical and echocardiographic parameters were recorded. LV shapes were classified on echocardiography, using basal septal 1/3 to posterior wall ratio: RSC = ratio >1.3 (extending to mid and distal septum), SS = ratio >1.3 (extending only to basal 1/3), and concentric = ratio ≤1.3. Longitudinal systolic and early diastolic SRs were measured from apical 4- and 2-chamber views (VVI 2.0; Siemens, Erlangen). Distribution of RSC, SS, and CH was 50%, 28%, and 22%, respectively. Patients with RSC were significantly younger (47 ± 12 vs 64 ± 10 and 57 ± 11, respectively) with lower hypertension (40% vs 71% and 67%, respectively) than patients with SS or CH (both p <0.001). Patients with RSC had lower global systolic (-0.99 ± 0.3 vs -1.05 ± 0.3 and -1.17 ± 0.3) and early diastolic SR (0.95 ± 0.4 vs 0.98 ± 0.3 and 1.16 ± 0.4) versus patients with SS and CH (in 1/s, both p <0.01), despite being much younger and less hypertensive. RSC was associated with abnormal global LV systolic (beta 0.16) and early diastolic (beta -0.17) SR (both p <0.01). In conclusion, patients with HC with RCS have significantly abnormal LV mechanics, despite being younger and less hypertensive. A combination of LV mechanics and shapes could help differentiate between genetically mediated and other causes of obstructive HC.

Perioperative outcomes of patients with hypertrophic cardiomyopathy undergoing non-cardiac surgery

Objective Due to their unique pathophysiological profile, patients with hypertrophic cardiomyopathy (HCM) undergoing non-cardiac surgery require additional attention to perioperative management. We sought to compare perioperative outcomes of patients with HCM undergoing non-cardiac surgery with a matched group patients without HCM. Methods This observational cohort study conducted at a tertiary care centre included patients with HCM (n=92, age 67 years, 54% men) undergoing intermediate-risk and high-risk non-cardiac surgeries between 1/2007 and 12/2013 (excluding <18 years, prior septal myectomy/alcohol ablation, low-risk surgery) who were 1:2 matched (based on age, gender, type and time of non-cardiac surgery) with patients without HCM (n=184, median age 65 years, 53% men). A composite endpoint (30-day postoperative death, myocardial infarction, stroke, in-hospital decompensated congestive heart failure (CHF) and rehospitalisation within 30 days) and postoperative atrial fibrillation (AF) were recorded. Results There was a significantly lower incidence of intraoperative hypotension/tachycardia in patients with HCM versus those without HCM (p<0.001). At 30 days postoperatively, 42 (15%) patients had composite events. Rates of 30-day death, MI or stroke were very low in patients with HCM (5%). However, a significantly higher proportion of patients with HCM met the composite endpoint versus patients without HCM (20 (22%) vs 22 (12%), p=0.03), driven by decompensated CHF. On logistic regression, HCM, high-risk non-cardiac surgery, high anaesthesia risk score and intraoperative duration of hypotension were independently associated with 30-day composite events (p<0.05). Conclusions Patients with HCM undergoing high-risk and intermediate-risk non-cardiac surgeries have a low perioperative event rate, at an experienced centre. However, they have a higher risk of composite events versus matched patients without HCM.

Prediction of sudden death risk in obstructive hypertrophic cardiomyopathy: Potential for refinement of current criteria

Background In patients with hypertrophic cardiomyopathy (HCM), the use of an implantable cardioverter defibrillator (ICD) can prevent sudden cardiac death (SCD). In patients with obstructive HCM, we sought to determine the prognostic utility of European Society of Cardiology (ESC) SCD risk score and to evaluate whether additional factors modulate SCD risk. Methods We studied 1809 consecutive patients with obstructive HCM (mean age, 50 ± 14 years; 63% males; mean maximal outflow tract gradient, 93 ± 40 mm Hg). Major SCD risk factors were recorded (0, 1, or ≥2) and % 5‐year ESC SCD risk score was calculated. The need for surgical myectomy and a composite endpoint (SCD and/or appropriate ICD discharge) were recorded. Results The distribution of major SCD risk factors was 0 in 65% of the patients, 1 in 26%, and ≥2 in 8%. The 5‐year ESC risk was low (<4%) in 65% of the patients, intermediate (4%‐6%) in 18%, and high (>6%) in 17%. Surgery was performed in 1160 patients (64%), and 361 (20%) had AF. At a mean of 8.8 ± 4 years, 169 patients had a composite event (154 SCDs). At 5 years, despite a wide range of expected events (2.5%‐9%), the observed events ranged from 4.6% to 5% across 3 SCD risk categories (Hosmer–Lemeshow P = .32). On multivariable competing‐risk analysis, myectomy (subdistribution hazard ratio [sHR], 0.69; 95% confidence interval [CI], 0.47‐0.83) was associated with lower risk of longer‐term composite events (P < .01), whereas ESC SCD risk score was not (sHR, 1.31; 95% CI, 0.75‐2.25; P = .36). Conclusions In patients with obstructive HCM, despite a wide range of expected 5‐year primary event rate, the observed primary events were similar across the 3 ESC SCD risk categories, with myectomy mitigating SCD risk. In patients with obstructive HCM, SCD risk may need to be refined for patients following myectomy.

Comparison of devices used in carotid artery stenting: A vascular quality initiative analysis of commonly used carotid stents and embolic protection devices

Data regarding efficacy of various stent and embolic protection device (EPD) combinations to prevent stroke during carotid artery stenting (CAS) is limited. We compared post‐procedure inpatient neurologic outcomes across various carotid stent‐EPD platforms recorded in the Vascular Quality Initiative (VQI) registry.

Prevalence of High On-Treatment (Aspirin and Clopidogrel) Platelet Reactivity in Patients with Critical Limb Ischemia ☆

OBJECTIVES The goal of this study is to establish the prevalence of high on-treatment platelet reactivity to aspirin (HPRA) and clopidogrel (HPRC) in patients with critical limb ischemia (CLI). BACKGROUND CLI is associated with an increased risk of death and cardiovascular events. Unlike other patient populations with atherosclerotic cardiovascular disease, previous studies failed to demonstrate a benefit of antiplatelet therapy in patients with CLI. METHODS From June 2014 to November 2016, we performed platelet reactivity studies for P2Y12 and thromboxane A2 (TXA2) inhibition in 100 CLI patients receiving daily treatment with aspirin and clopidogrel. P2Y12 inhibition was measured by two assays: vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 assays. HPRC was defined as VerifyNow P2Y12 reactive units (PRU) >208 and VASP-platelet reactivity index (VASP-PRI) >50%. TXA2 inhibition was measured with the VerifyNow aspirin test and HPRA was defined as aspirin reaction units (ARU) >550. RESULTS Mean age was 67±11 years, 50% were male, 80% had diabetes mellitus, and 26% had chronic renal insufficiency. Thirty-three percent of patients had a PRU >208 and 46% a VASP-PRI >50%. HPRC was present in 26% of patients based on the criteria of both a PRU >208 and VASP-PRI >50%. HPRA was present in 25% of patients. The overall prevalence of HPR to ASA or clopidogrel was 35% and HPR to both drugs was present in 8% of patients. Clinical characteristics were similar between groups. CONCLUSIONS HPR to aspirin or clopidogrel is highly prevalent in patients with CLI. Nearly one in ten patients with CLI is a hyporesponder to both aspirin and clopidogrel.

Long term outcomes of drug-eluting stents versus bare metal stents in saphenous vein graft interventions. Evidence from a meta-analysis of randomized controlled trials

BACKGROUND The optimal stent for use in saphenous vein graft (SVG) intervention is still debatable. Multiple randomized trials have compared drug-eluting stents (DES) to bare metal stents (BMS) in SVG interventions with conflicting results. METHODS Authors searched the online databases for randomized controlled trials (RCTs) comparing DES to BMS in SVG percutaneous coronary interventions (PCI). We performed a meta-analysis using a random effects model to calculate the odds ratio for outcomes of interest. RESULTS Authors studied six RCTs that included 1592 patients undergoing PCI of SVG. The mean follow up was 42 months. Patients mean age was the same in both groups: 70.3 years in the DES group (approximately 93.3% male) and 70.3 years in the BMS group (approximately 93.8% male). Vein graft age was 13.4 years in the DES PCI arm vs. 13.4 years in the BMS PCI arm. Four of the six trials reported data on embolic protection device use: 67% (303/452) in the DES arm vs. 67.9% (309/455) in the BMS arm. The primary outcome of long-term all-cause mortality was not different between DES vs. BMS (15.2% vs. 14.1%, OR 1.12, 95% CI 0.67-1.88; P = 0.66). Secondary outcomes were also similar between DES and BMS: major adverse cardiovascular events (31.6% vs. 33.1%, OR 0.79, 95% CI 0.45-1.38; P = 0.41); cardiac death (9% vs. 8.6%, OR 1.12, 95% CI 0.55-2.30; P = 0.75); myocardial infarction (8% vs. 9.5%, OR 0.84, 95% CI 0.47-1.51; P = 0.57); target lesion revascularization (16.4% vs. 14.4%, OR 0.98, 95% CI 0.50-1.92; P = 0.95); and target vessel revascularization (19% vs. 19.4%, OR 0.75, 95% CI 0.41-1.34; P = 0.33). CONCLUSION At a mean follow-up of 42 months, no difference was observed in clinical outcomes between DES and BMS in SVG interventions.