Santhosh K. G. Koshy

Adaptive-outward and maladaptive-inward arterial remodeling measured by intravascular ultrasound in hyperhomocysteinemia and diabetes.

Background: Coronary artery remodeling implies structural changes in the vessel wall in response to various pathophysiologic conditions. However, the classification of remodeling is unclear. We hypothesized that the adaptive, positive-outward remodeling is a reactive and compensatory response to the stress. The maladaptive negative-inward constrictive remodeling is a passive atherosclerotic condition in which the vessel becomes stiffer. Methods: Patients with atherosclerotic lesions underwent intravascular ultrasound (IVUS) scans. The size of the vessels distal to and proximal to plaques were analyzed by IVUS. Diabetes was created in mice by an intraperitoneal injection of alloxan (65 mg/kg). To reduce remodeling, mice received ciglitazone, an agonist of peroxisome proliferators activated receptor-g (PPARg) in drinking water. After 8 weeks, atherosclerotic vessels were analyzed for collagen and elastin. Results: IVUS data suggest an adaptive coronary arterial remodeling was a positive compensatory response to various pathologic stimuli; for example, with the deposition of atherosclerotic plaque, coronary arterial segments enlarged to maintain luminal area. This phenomenon was commonly observed during the initial phases of the development of atherosclerosis. However, negative coronary artery remodeling, or a decrease in vessel area with the formation of atherosclerotic plaque, was maladaptive and was associated with smoking, hypertension, hyperhomocysteinemia, diabetes mellitus, and also after percutaneous coronary interventions (restenosis). In diabetic mice, there was increased collagen and decreased elastin contents; however, treatment with ciglitazone ameliorated the decrease in elastin contents. Conclusion: Global enlargement of the coronary vascular tree occurs during pressure and volume overload associated with ventricular hypertrophic states such as athletic conditioning, hypertensive heart disease, and dilated cardiomyopathy. On the other hand, maladaptive coronary arterial remodeling occurs in patients with severe deconditioning, diabetes mellitus, after coronary artery bypass surgery, and in some instances, postintervention.

Intracardiac echocardiography: clinical utility and application.

Intracardiac echocardiography (ICE) broadens the spectrum of available echocardiographic techniques and provides the operator direct visualization of cardiac structures in real time. ICE has clear advantages over fluoroscopy, transthoracic echocardiography, and transesophageal echocardiography as the imaging modality of choice in the cardiac catheterization and electrophysiological laboratories. With the development of steerable phased array catheters with low frequency and Doppler qualities, there is marked improvement in visualization of left‐sided structures from the right heart. Appropriate utilization of ICE is likely to maximize safety and efficacy of complex interventional procedures and may improve patient outcomes. Future advances in ICE imaging will further improve the ease of device guidance and, in combination with new imaging modalities, could dramatically improve other applications of echocardiography which may result in improved patient outcomes. This review describes the technical evolution of ICE, the use of ICE in guiding percutaneous interventional procedures and possible future applications of ICE in the ever‐growing field of interventional cardiology. (Echocardiography 2011;28:582‐590)

Remodeling of Coronary Arteries in Diabetic Patients - An Intravascular Ultrasound Study

Background: Coronary artery remodeling is a structural change in the vessel wall and typically in response to atherosclerotic plaque. The nature of coronary remodeling has been described in different clinical situations. However, remodeling characteristics of coronary arteries of diabetic patients have never been studied. Hypothesis: We tested the hypothesis that positive remodeling of coronary artery in response to atherosclerotic plaque in diabetic patients would be less compared to nondiabetic patients. Methods: Coronary intravascular ultrasound analysis of data in 26 consecutive patients (12 diabetic and 14 nondiabetic) was performed. Linear regression analyses of vessel area versus plaque area were carried out to establish a relation between the degree of plaque and the extent of remodeling in diabetic and nondiabetic groups. Results: The positive remodeling quantified as the slope of the regression line was similar in both the groups (diabetic group 1.32 and nondiabetic group 0.80) when all segments with different plaque areas were considered (P > 0.05). However, the diabetic group had greater positive remodeling in segments with plaque area less than 55%, as the slope for diabetic group was 2.01 and nondiabetic group was 1.40 (P < 0.05). Conclusions: Both the diabetic and nondiabetic patients had positive remodeling in response to atherosclerotic plaque formation. Diabetics had greater positive remodeling in the early stages of atherosclerosis compared to nondiabetics, thus providing evidence against our hypothesis. The adverse clinical outcomes in diabetics may not be due to inadequate positive remodeling of coronary arteries as previously thought. (ECHOCARDIOGRAPHY, Volume 21, February 2004)

Safety and Efficacy of Ibutilide in Cardioversion of Atrial Flutter and Fibrillation

This article reviews the safety and efficacy of ibutilide for use in patients with atrial fibrillation and flutter. Ibutilide, a class III antiarrhythmic agent, is primarily used for conversion of atrial flutter and fibrillation and is a good alternative to electrical cardioversion. Ibutilide has a conversion rate of up to 75% to 80% in recent-onset atrial fibrillation and flutter; the conversion rate is higher for atrial flutter than for atrial fibrillation. It is also safe in the conversion of chronic atrial fibrillation/flutter among patients receiving oral amiodarone therapy. Ibutilide pretreatment facilitates transthoracic defibrillation and decreases the energy requirement of electrical cardioversion by both monophasic and biphasic shocks. Pretreatment with ibutilide before electrical defibrillation has a conversion rate of 100% compared with 72% with no pretreatment. Ibutilide is also safe and efficient in the treatment of atrial fibrillation in patients who have had cardiac surgery, and in accessory pathway–mediated atrial fibrillation where the conversion rate of ibutilide is as high as 95%. There is up to a 4% risk of torsade de pointes and a 4.9% risk of monomorphic ventricular tachycardia. Hence, close monitoring in an intensive care unit setting is warranted during and at least for 4 hours after drug infusion. The anticoagulation strategy is the same as for any other mode of cardioversion.

Current Oral Antiplatelets: Focus Update on Prasugrel

Platelet activation and aggregation plays an integral role in the pathogenesis of acute coronary syndrome (ACS). The mainstay of ACS treatment revolves around platelet inhibition. It is known that greater platelet inhibition results in better ischemic outcomes; hence, focus in drug development has been to create more potent inhibitors of platelet aggregation. Prasugrel, a potent, third-generation thienopyridine, was approved by the US Food and Drug Administration in July 2009 for its use in ACS and percutaneous coronary intervention. The addition of prasugrel to aspirin for dual antiplatelet therapy has been shown to reduce the ischemic outcomes compared with clopidogrel and aspirin in combination. However, being a more potent antiplatelet agent, prasugrel increases the risk of bleeding, especially in those patients who are at a higher risk of bleeding complications. Elderly patients ≥75 years, patients who weigh ≥60 kg, and patients with a history of stroke or transient ischemic attack are at a higher risk of bleeding complications when prasugrel is used in combination with aspirin. Newer antiplatelets currently are being clinically evaluated to assess their efficacy in reducing ischemic events without increasing the bleeding risk.

Association of Pre-Operative Albuminuria with Post-Operative Outcomes after Coronary Artery Bypass Grafting.

The effect on post-operative outcomes after coronary artery bypass graft(CABG) surgery is not clear. Among 17,812 patients who underwent CABG during October 1,2006-September 28,2012 in any Department of US Veterans Affairs(VA) hospital, we identified 5,968 with available preoperative urine albumin-creatinine ratio(UACR) measurements. We examined the association of UACR<30, 30–299 and >=300 mg/g with 30/90/180/365-day and overall all-cause mortality, and hospitalization length >10 days, and with acute kidney injury(AKI). Mean ± SD baseline age and eGFR were 66 ± 8 years and 77 ± 19 ml/min/1.73 m2, respectively. 788 patients(13.2%) died during a median follow-up of 3.2 years, and 26.8% patients developed AKI(23.1%-Stage 1; 2.9%-Stage 2; 0.8%-Stage 3) within 30 days of CABG. The median lengths of stay were 8 days(IQR: 6–13 days), 10 days(IQR: 7–14 days) and 12 days(IQR: 8–19 days) for groups with UACR < 30 mg/g, 30–299 mg/g and ≥300 mg/g, respectively. Higher UACR conferred 72 to 85% higher 90-, 180-, and 365-day mortality compared to UACR<30 mg/g (odds ratio and 95% confidence interval for UACR≥300 vs. <30 mg/g: 1.72(1.01–2.95); 1.85(1.14–3.01); 1.74(1.15–2.61), respectively). Higher UACR was also associated with significantly longer hospitalizations and higher incidence of all stages of AKI. Higher UACR is associated with significantly higher odds of mortality, longer post-CABG hospitalization, and higher AKI incidence.

Predialysis coronary revascularization and postdialysis mortality

Objectives: Coronary artery bypass grafting (CABG) is associated with better survival than percutaneous coronary intervention (PCI) in patients with mild‐to‐moderate chronic kidney disease (CKD) and end‐stage renal disease (ESRD). However, the optimal strategy for coronary artery revascularization in patients with advanced CKD who transition to ESRD is unclear. Methods: We examined a contemporary national cohort of 971 US veterans with incident ESRD who underwent first CABG or PCI up to 5 years before dialysis initiation. We examined the association of a history of CABG versus PCI with all‐cause mortality following transition to dialysis using Cox proportional hazards models adjusted for time between procedure and dialysis initiation, sociodemographics, comorbidities, and medications. Results: In total, 582 patients underwent CABG and 389 patients underwent PCI. The mean age was 64 ± 8 years, 99% of patients were male, 79% were white, 19% were African American, and 84% had diabetes. The all‐cause post‐dialysis mortality rates after CABG and PCI were 229 per 1000 patient‐years (95% confidence interval [CI], 205‐256) and 311 per 1000 patient years (95% CI, 272‐356), respectively. Compared with PCI, patients who underwent CABG had 34% lower risk of death (multivariable adjusted hazard ratio, 0.66; 95% CI, 0.51‐0.86, P = .002) after initiation of dialysis. Results were similar in all subgroups of patients stratified by age, race, type of intervention, presence/absence of myocardial infarction, congestive heart failure, and diabetes. Conclusions: CABG in patients with advanced CKD was associated lower risk of death after initiation of dialysis compared with PCI.

Acute kidney injury following coronary revascularization procedures in patients with advanced CKD

Background Previous studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD. Methods We examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses. Results A total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001]. Conclusion CABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.

Hyperlipidemia: Management with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors

Coronary artery disease is the leading cause of death in United States. Hyperlipidemia is an independent and potentially reversible risk factor for coronary artery disease. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, collectively known as statins, have been the mainstay of pharmacologic therapy. Their availability, ease of administration, low cost, and strong evidence behind safety and efficacy makes them one of the most widely prescribed lipid-lowering agents. However, some patients may be intolerant to statins, and few others suffer from very high serum levels of cholesterol in which statin therapy alone or in combination with other cholesterol-lowering agents is insufficient in reducing serum lipid levels to achieve desired levels. In 2015, the Food and Drug Administration approved a new family of lipid-lowering agents, collectively known as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. PCSK9 inhibitors are biologically active molecules that decrease serum low-density lipoprotein cholesterol compared with statin therapy alone. They serve as an alternative to statins for patients who are intolerant to statin or as supplemental therapy in those patients for whom lower levels in serum low-density lipoprotein cholesterol are not achieved by statins alone. This article discusses PCSK9 inhibitors, their mechanism of action, indications, efficacy, safety, costs and limitations.

When the gold standard is not always golden: The value of invasive hemodynamic assessment to overcome the pitfalls of echocardiography in challenging cases of mitral stenosis

Mitral stenosis is a uncommon valvular lesion in the developed countries. Noninvasive evaluation is the first‐line modality for assessment of mitral stenosis, however the noninvasive methods may have limitations in certain cases. Invasive hemodynamics can be used as adjunct tool for assessment of mitral stenosis in such difficult cases. Mitral valve using three‐dimensional planimetry is a promising technique for assessment of mitral stenosis.