Vedant Pargaonkar

Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease

OBJECTIVES This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease. BACKGROUND Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation. METHODS We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia. RESULTS All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn. CONCLUSIONS Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

Surgical Unroofing of Hemodynamically Significant Left Anterior Descending Myocardial Bridges

BACKGROUND Left anterior descending artery myocardial bridges (MBs) range from clinically insignificant incidental angiographic findings to a potential cause of sudden cardiac death. Within this spectrum, a group of patients with isolated, symptomatic, and hemodynamically significant MBs despite maximally tolerated medical therapy exist for whom the optimal treatment is controversial. We evaluated supraarterial myotomy, or surgical unroofing, of the left anterior descending MBs as an isolated procedure in these patients. METHODS In 50 adult patients, we prospectively evaluated baseline clinical characteristics, risk factors, and medications for coronary artery disease, relevant diagnostic data (stress echocardiography, computed tomography angiography, stress coronary angiogram with dobutamine challenge for measurement of diastolic fractional flow reserve, and intravascular ultrasonography), and anginal symptoms using the Seattle Angina Questionnaire. These patients then underwent surgical unroofing of their left anterior descending artery MBs followed by readministration of the Seattle Angina Questionnaire at 6.6-month (range, 2 to 13) follow-up after surgery. RESULTS Dramatic improvements were noted in physical limitation due to angina (52.0 versus 87.1, p < 0.001), anginal stability (29.6 versus 66.4, p < 0.001), anginal frequency (52.1 versus 84.7, p < 0.001), treatment satisfaction (76.1 versus 93.9, p < 0.001), and quality of life (25.0 versus 78.9, p < 0.001), all five dimensions of the Seattle Angina Questionnaire. There were no major complications or deaths. CONCLUSIONS Surgical unroofing of carefully selected patients with MBs can be performed safely as an independent procedure with significant improvement in symptoms postoperatively. It is the optimal treatment for isolated, symptomatic, and hemodynamically significant MBs resistant to maximally tolerated medical therapy.

Surgical unroofing of hemodynamically significant myocardial bridges in a pediatric population

Background Although myocardial bridges (MBs) are traditionally regarded as incidental findings, it has been reported that adult patients with symptomatic MBs refractory to medical therapy benefit from unroofing. However, there is limited literature in the pediatric population. The aim of our study was to evaluate the indications and outcomes for unroofing in pediatric patients. Methods We retrospectively reviewed all pediatric patients with MB in our institution who underwent surgical relief. Clinical characteristics, relevant diagnostic data, intraoperative findings, and postoperative outcomes were evaluated. Results Between 2012 and 2016, 14 pediatric patients underwent surgical unroofing of left anterior descending artery MBs. Thirteen patients had anginal symptoms refractory to medical therapy, and 1 patient was asymptomatic until experiencing aborted sudden cardiac arrest during exercise. Thirteen patients underwent exercise stress echocardiography, all of which showed mid‐septal dys‐synergy. Coronary computed tomography imaging confirmed the presence of MBs in all patients. Intravascular ultrasound imaging confirmed the length of MBs: 28.2 ± 16.3 mm, halo thickness: 0.59 ± 0.24 mm, and compression of left anterior descending artery at resting heart rate: 33.0 ± 11.6%. Invasive hemodynamic assessment with dobutamine confirmed the physiologic significance of the MBs with diastolic fractional flow reserve: 0.59 ± 0.13. Unroofing was performed with the patient under cardiopulmonary bypass (CPB) in the initial 9 cases and without CPB in the subsequent 5 cases. All patients were discharged without complications. The 13 symptomatic patients reported resolution of symptoms on follow‐up, and improvement in symptoms and quality of life was documented using the Seattle Angina Questionnaire version 7. Conclusions Unroofing of MBs can be safely performed in pediatric patients, with or without use of CPB. In symptomatic patients, unroofing can provide relief of symptoms refractory to medical therapy.

Examining QRS amplitude criteria for electrocardiographic left ventricular hypertrophy in recommendations for screening criteria in athletes

BACKGROUND Current guidelines for interpretation of the ECGs of athletes recommend that isolated R and S wave amplitudes that exceed traditional criteria for left ventricular hypertrophy be accepted as a physiological response to exercise training. This is based on training and echocardiographic studies but not on long term follow up. Demonstration of the prognostic characteristics of the amplitude criteria in a non-athletic population could support the current guidelines. OBJECTIVE To evaluate the prognostic value of the R and S wave voltage criteria for electrocardiographic left ventricular hypertrophy (ECG-LVH) in an ambulatory clinical population. SUBJECTS AND METHODS The target population consisted of 20,903 ambulatory subjects who had ECGs recorded between 1987 and 1999 and were followed for cardiovascular death until 2013. During the mean follow up of 17 years, there were 881 cardiovascular deaths. RESULTS The mean age was 43 ± 10, 91% were male and 16% were African American. Of the 2482 (12%) subjects who met the Sokolow-Lyon criteria, 241 (1.2%) subjects with left ventricular (LV) strain had an HR of 5.4 (95% CI 4.1-7.2, p<0.001), while 2241 (11%) subjects without strain had an HR of 1.4 (95% CI 1.2-1.8, p<0.001). Of the 4836 (23%) subjects who met the Framingham voltage criteria, 350 (2%) subjects with LV strain had an HR of 5.1 (95% CI 4.0-6.5, p<0.001), while 4486 (22%) subjects without strain had an HR of 1.1 (95% CI 0.9-1.3, p=0.26). The individual components of the Romhilt-Estes had HRs ranging from 1.4 to 3.6, with only the voltage component not being significant (HR 1.1, 95% CI 0.9-1.5, p=0.35). CONCLUSIONS This study demonstrates that the R and S wave voltage criteria components of most of the original classification schema for electrocardiographic left ventricular hypertrophy are not predictive of CV mortality. Our findings support the current guidelines for electrocardiographic screening of athletes.

Impact of Asymmetric Dimethylarginine on Coronary Physiology Early After Heart Transplantation

Cardiac allograft vasculopathy is a major cause of long-term graft failure following heart transplantation. Asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction, has been mechanistically implicated in the development of cardiac allograft vasculopathy, but its impact on coronary physiology early after transplantation is unknown. Invasive indices of coronary physiology, namely, fractional flow reserve (FFR), the index of microcirculatory resistance, and coronary flow reserve, were measured with a coronary pressure wire in the left anterior descending artery within 8 weeks (baseline) and 1 year after transplant. Plasma levels of ADMA were concurrently assayed using high-performance liquid chromatography. In 46 heart transplant recipients, there was a statistically significant correlation between elevated ADMA levels and lower FFR values at baseline (r = -0.33; p = 0.024); this modest association persisted 1 year after transplant (r = -0.39; p = 0.0085). Patients with a baseline FFR <0.90 (a prognostically validated cutoff) had significantly higher baseline ADMA levels (0.63 ± 0.16 vs 0.54 ± 0.12 µM; p = 0.034). Baseline ADMA (odds ratio 1.80 per 0.1 µM; 95% confidence interval 1.07 to 3.03; p = 0.027) independently predicted a baseline FFR <0.90 after multivariable adjustment. Even after dichotomizing ADMA (≥0.60 µM, provides greatest diagnostic accuracy by receiver operating characteristic curve), this association remained significant (odds ratio 7.52, 95% confidence interval 1.74 to 32.49; p = 0.006). No significant relationship between ADMA and index of microcirculatory resistance or coronary flow reserve was detected. In conclusion, baseline ADMA was a strong independent predictor of FFR <0.90, suggesting that elevated ADMA levels are associated with abnormal epicardial function soon after heart transplantation.

THE DIAGNOSTIC VALUE OF STRESS ECHOCARDIOGRAPHY AND ELECTROCARDIOGRAPHY IN IDENTIFYING OCCULT CORONARY ABNORMALITIES IN PATIENTS WITH ANGINA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE

While >20% of patients presenting to the cath lab with angina have no obstructive CAD, a majority (77%) have occult coronary abnormalities (endothelial dysfunction, microvascular dysfunction (MVD), and myocardial bridging (MB)), which may explain their symptoms. The ability of stress echocardiogram

Accuracy of non-invasive stress testing in women and men with angina in the absence of obstructive coronary artery disease

OBJECTIVE While >20% of patients presenting to the cardiac catheterization laboratory with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality (endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB)). There are little data regarding the ability of noninvasive stress testing to identify these occult abnormalities in patients with angina in the absence of obstructive CAD. METHODS We retrospectively evaluated 155 patients (76.7% women) with angina and no obstructive CAD who underwent stress echocardiography and/or electrocardiography before angiography. We evaluated Duke treadmill score, heart rate recovery (HRR), metabolic equivalents, and blood pressure response. During angiography, patients underwent invasive testing for endothelial dysfunction (decrease in epicardial coronary artery diameter >20% after intracoronary acetylcholine), MVD (index of microcirculatory resistance ≥25), and intravascular ultrasound for the presence of an MB. RESULTS Stress echocardiography and electrocardiography were positive in 58 (43.6%) and 57 (36.7%) patients, respectively. Endothelial dysfunction was present in 96 (64%), MVD in 32 (20.6%), and an MB in 83 (53.9%). On multivariable logistic regression, stress echo was not associated with any abnormality, while stress ECG was associated with endothelial dysfunction. An abnormal HRR was associated with endothelial dysfunction and MVD, but not an MB. CONCLUSION Conventional stress testing is insufficient for identifying occult coronary abnormalities that are frequently present in patients with angina in the absence of obstructive CAD. A normal stress test does not rule out a non-obstructive coronary etiology of angina, nor does it negate the need for comprehensive invasive testing.

Myocardial bridging is associated with exercise-induced ventricular arrhythmia and increases in QT dispersion

A myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort.

SEX DIFFERENCES IN THE RISK FACTORS FOR ENDOTHELIAL AND MICROVASCULAR DYSFUNCTION IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE

Background: While >20% of patients presenting to the cath lab with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality, including endothelial dysfunction and/or microvascular dysfunction (MVD), which may explain their symptoms. We studied

EFFECT OF SURGICAL UNROOFING OF A MYOCARDIAL BRIDGE ON EXERCISE INDUCED QT INTERVAL DISPERSION AND ANGINAL SYMPTOMS IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE

Prior studies have shown that exercise significantly increases the rate corrected QT dispersion (QTcd) in patients with a myocardial bridge (MB), suggesting repolarization abnormalities due to ischemia in the area perfused by the bridged artery. We studied the effect of surgical unroofing on