Raviteja R. Guddeti

Coronary Artery Tortuosity in Spontaneous Coronary Artery Dissection Angiographic Characteristics and Clinical Implications

Background—Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute coronary syndrome. The angiographic characteristics of SCAD are largely undetermined. The goal of this study was to determine the prevalence of coronary tortuosity in SCAD and whether it may be implicated in the disease. Methods and Results—Patients with confirmed SCAD (n=246; 45.3±8.9 years; 96% women) and 313 control patients without SCAD or coronary artery disease who underwent coronary angiography were included in this case–control study. Angiograms were reviewed for coronary tortuosity and assigned a tortuosity score. Tortuosity was common in patients presenting with their first SCAD event (78% versus 17% in controls; P<0.0001; tortuosity score, 4.41±1.73 versus 2.33±1.49 in controls; P<0.0001) despite a low prevalence of hypertension (34%). Recurrent SCAD (n=40) occurred within segments of tortuosity in 80% of cases. Severe tortuosity (≥2 consecutive curvatures ≥180°) was associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95% confidence interval, 0.99–8.29; P=0.05). Tortuosity score >5 was associated with a trend toward higher risk of recurrent SCAD (P=0.16). Prespecified angiographic markers of tortuosity including corkscrew appearance and multivessel symmetrical tortuosity were associated with extracoronary vasculopathy including fibromuscular dysplasia (P<0.05 for both). Conclusions—Coronary artery tortuosity is highly prevalent in the SCAD population and is associated with recurrent SCAD. Recurrent SCAD most often occurs within segments of tortuosity. Angiographic features of SCAD are associated with extracoronary vasculopathy, including fibromuscular dysplasia. These findings suggest that coronary tortuosity may serve as a marker or potential mechanism for SCAD.

Treating coronary disease and the impact of endothelial dysfunction.

Ischemic heart disease is the leading cause of morbidity and mortality throughout the world. Many clinical trials have suggested that lifestyle and pharmacologic interventions are effective in attenuating atherosclerotic disease progression and events development. However, an individualized approach with careful consideration to comprehensive vascular health is necessary to perform successful intervention strategies. Endothelial dysfunction plays a pivotal role in the early stage of atherosclerosis and is also associated with plaque progression and occurrence of atherosclerotic complications. The assessment of endothelial function provides us with important information about individual patient risk, progress and vulnerability of disease, and guidance of therapy. Thus, the application of endothelial function assessment might enable clinicians to innovate ideal individualized medicine. In this review, we summarize the current knowledge on the impact of pharmacological therapies for atherosclerotic cardiovascular disease on endothelial dysfunction, and argue for the utility of non-invasive assessment of endothelial function aiming at individualized medicine.

Secondary Prevention Strategy of Cardiovascular Disease Using Endothelial Function Testing

Over the past decades, secondary prevention of cardiovascular (CV) disease has improved and considerably reduced mortality rates. However, there remains a high-rate of new or recurrent CV events in those with established atherosclerotic vascular diseases. Although most of the prevailing therapies target the conventional risk factors, there is notable interindividual heterogeneity in adaptation to risk factors and response to therapies, which affects efficacy. It is desirable to have a methodology for directly assessing the functional significance of atherogenesis, and for managing individual patients based on their comprehensive vascular health. Endothelial function plays a pivotal role in all stages of atherosclerosis, from initiation to atherothrombotic complication. Endothelial function reflects the integrated effect of all the atherogenic and atheroprotective factors present in an individual, and is therefore regarded as an index of active disease process and a significant risk factor for future CV events. Moreover, improvement in endothelial function is associated with decreased risk of CV events, even in the secondary prevention setting. The introduction of endothelial function assessment into clinical practice may trigger the development of a more tailored and personalized medicine and improve patient outcomes. In this review, we summarize current knowledge on the contribution of endothelial dysfunction to atherosclerotic CV disease in the secondary prevention setting. Finally, we focus on the potential of an endothelial function-guided management strategy in secondary prevention.

Predictive value of endothelial function by noninvasive peripheral arterial tonometry for coronary artery disease.

BackgroundEndothelial dysfunction is a key step in the initiation and progression of atherosclerosis and subsequent cardiovascular complications. We examined whether peripheral endothelial function, as assessed by fingertip reactive hyperemia-peripheral arterial tonometry (RH-PAT), can provide additional clinical value to traditional risk factors for cardiovascular diseases in predicting coronary artery disease (CAD). MethodsWe included 118 stable patients who were referred for coronary angiography for chest pain evaluation or due to abnormal stress test results. A natural logarithmic value of the RH-PAT index (Ln_RHI) was obtained before cardiac catheterization by an independent operator. Significant CAD was defined as luminal stenosis of at least 70% (≥50% at left main) and/or fractional flow reserve of up to 0.80 in one or more major coronary arteries or their major branches. ResultsLevels of Ln_RHI were significantly lower in patients with CAD (n=60) compared with patients without CAD (n=58; 0.69±0.29 vs. 0.88±0.27, P<0.001). Ln_RHI was significantly associated with CAD independent from traditional risk factors (odds ratio for a 0.1 decrease in Ln_RHI=1.25, 95% confidence interval: 1.04–1.52, P=0.01). The net reclassification index was improved when Ln_RHI was added to traditional risk factors (0.62, 95% confidence interval: 0.27–0.97, P=0.001). ConclusionPeripheral endothelial function, as assessed by RH-PAT, improved risk stratification when added to traditional risk factors. RH-PAT is potentially useful for identifying patients at high risk for CAD.

Clinical Implications of Intracoronary Imaging in Cardiac Allograft Vasculopathy

Despite improvements in survival and outcomes, cardiac allograft vasculopathy (CAV), a unique form of coronary artery disease, continues to remains the leading cause of late morbidity and mortality in heart transplantation (HTx) recipients and accounts for ≈30% of all-cause mortality in this group.1 CAV can develop at any stage after HTx with an incidence of ≈7% within the first year of transplantation and 30% within 5 years.2 CAV is clinically silent and asymptomatic in its initial stages, making early diagnosis particularly challenging. Annual coronary angiography is currently the imaging modality of choice for screening and surveillance of graft coronary arteries for signs of CAV.3 However, low sensitivity of coronary angiography for detecting early-stage CAV necessitates the use of more advanced intracoronary imaging to diagnose the disease in its initial stages. Recent advances in invasive coronary imaging such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have shown promising results in detecting subangiographic CAV, predicting prognosis and guiding therapy.4–6 The current article reviews the present state and future directions for the use of intracoronary imaging in the diagnosis, prognosis, and treatment of CAV. Several invasive and noninvasive imaging tools have been used to screen and diagnose CAV. Some of the noninvasive tests such as dobutamine stress echocardiography, myocardial perfusion imaging (exercise and pharmacological), cardiac MRI, and coronary computed tomography angiography have been studied extensively for this purpose.7–9 Although these noninvasive tests are highly specific for angiographic CAV, they lack sensitivity in detecting subangiographic CAV.7 The diffuse nature of CAV may result in inability to identify differences in radionuclide uptake in myocardial scintigraphy testing. A 2014 meta-analysis by Wever-Pinzon et al9 demonstrated that compared with coronary angiography, coronary computed tomography angiography was 97% sensitive for detecting any CAV. However, when …

Proliferation of Coronary Adventitial Vasa Vasorum in Patients With Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is one of the underlying mechanisms of acute coronary syndrome and sudden cardiac death, especially in young women. Although hemorrhage from vasa vasorum (VV) has been suggested as a possible mechanism of SCAD [(1)][1], no study has evaluated the

Clinical usefulness of nonhyperemic baseline Pd/Pa as a hybrid baseline Pd/Pa-fractional flow reserve strategy.

ObjectiveThe ratio of basal distal intracoronary pressure (Pd) and aortic pressure (Pa) is a nonhyperemic index for the severity of coronary artery stenosis. The aim of the current study was to evaluate the clinical usefulness of a hybrid baseline Pd/Pa–fractional flow reserve (FFR) strategy in reducing the need for hyperemia. MethodsIn this study, 570 lesions from 527 consecutive patients who had both baseline Pd/Pa and FFR determined were evaluated retrospectively. To evaluate the hybrid baseline Pd/Pa–FFR approach, patients were categorized into treatment, deferral, and undetermined groups on the basis of their baseline Pd/Pa. Thereafter, patients in the undetermined group were assigned to FFR-guided treatment or deferral on the basis of an FFR cutoff value of 0.80 or lower. Major adverse cardiac events were evaluated in a median of 48.8 months (interquartile range, 35.0–66.4). ResultsA hybrid strategy using a deferral baseline Pd/Pa value of 1.00 (negative predictive value of 100%) and a treatment baseline Pd/Pa value of 0.86 or lower (positive predictive value of 100%), and limiting adenosine to a baseline Pd/Pa value between 0.87 and 0.99 would prevent the need for vasodilator drugs in 14.6% of lesions (14.0% patients), maintaining 100% agreement with an FFR-only strategy. However, adenosine-free lesions are increased to 59.6%, with 91% agreement. There was no difference in the major adverse cardiac event-free survival rate at 5 years between baseline Pd/Pa-guided and FFR-guided treatment patients (70.8 vs. 76.3%, P=0.63), or between baseline Pd/Pa-guided and FFR-guided deferral patients (71.3 vs. 82.4%, P=0.99). ConclusionThe current study reports a range of baseline Pd/Pa values that can predict myocardial ischemia without the need for inducing hyperemia. Adoption of this hybrid baseline Pd/Pa–FFR approach can reduce the need for drug-induced hyperemia.

Attenuation in Peripheral Endothelial Function After Continuous Flow Left Ventricular Assist Device Therapy Is Associated With Cardiovascular Adverse Events

BACKGROUND Patients with heart failure (HF) have abnormal endothelial function. Although use of a continuous flow left ventricular assist device (CF-LVAD) results in significant hemodynamic improvement, the effects on systemic endothelial function are unclear. METHODS AND RESULTS Eighteen HF patients with CF-LVAD implantation were included in this prospective observational study. We measured reactive hyperemia index (RHI) before and after CF-LVAD implantation to evaluate sequential changes in endothelial function. Patients were followed clinically for the occurrence of adverse cardiovascular events, a composite of death, thrombosis, bleeding, HF, renal failure, and arrhythmia. Preoperative RHI was 1.77±0.39. Early in the postoperative period (7-14 days after operation) RHI significantly decreased to 1.19±0.31 (P<0.001, compared with preoperative RHI). At first and second follow-up (4-6 weeks and 3-7 months after operation) RHI remained lower at 1.48±0.50 (P=0.030) and 1.26±0.37 (P=0.002), respectively, compared with preoperative RHI. The decrease in early postoperative RHI relative to preoperative RHI was significantly associated with adverse cardiovascular events after CF-LVAD (age-adjusted risk ratio for 0.25 decrease in RHI, 1.35; 95% confidence interval: 1.13-1.62, P=0.001). CONCLUSIONS Peripheral endothelial function had a significant and persistent decline up to 5 months following implantation of CF-LVAD, and this decline was associated with adverse cardiovascular events. These findings may provide insight into some of the vascular complications following CF-LVAD in HF patients.

Left Internal Mammary Artery Versus Coronary Stents: Impact on Downstream Coronary Stenoses and Conduit Patency

Background The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery (LIMA) versus percutaneous coronary intervention with bare metal stent (BMS) or drug eluting stent (DES). Methods and Results A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography (QCA; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan–Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow‐up angiogram compared with BMS and DES (hazard ratio [HR] [95% CI], 0.34; [0.20–0.59]; P=0.0002; and HR [95% CI], 0.39; [0.20–0.79]; P=0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES (HR [95% CI], 0.18; [0.12–0.28]; P<0.001; and HR [95% CI], 0.27; [0.16–0.46]; P<0.001, respectively). BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES, but the difference did not reach statistical significance (HR [95% CI], 1.13; [0.57–2.36]; P=0.73; and HR [95% CI], 1.46; [0.88–2.50]; P=0.14, respectively). Conclusions LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES.

Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial.

Objectives Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow. Methods In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified. Results Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (−17 (−26, −10) vs 26 (−15, 134); p=0.02 and −17 (−38, 14) vs 107 (2, 446); p=0.007, respectively). Conclusions Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI. Trial registration number NCT00586820; Results.