Nayan Agarwal

Identification and Quantification of Patent Foramen Ovale–Mediated Shunts: Echocardiography and Transcranial Doppler

Once deemed benign, patent foramen ovale (PFO)-mediated right-to-left shunting has now been linked to stroke, migraine, and hypoxemia. Contrast transesophageal echocardiography is considered the standard technique for identifying a PFO, allowing visualization of the atrial septal anatomy and differentiation from non-PFO right-to-left shunts. Transthoracic echocardiography is the most common method for PFO imaging, being cost-effective, but has the lowest sensitivity. Transcranial Doppler is highly sensitive but is unable to differentiate cardiac from pulmonary shunts; it is the best method to quantitate shunt severity, being more sensitive than transthoracic or transesophageal echocardiography so is our preferred screening method for PFO.

Staged versus index procedure complete revascularization in ST‐elevation myocardial infarction: A meta‐analysis

BACKGROUND Complete revascularization of patients with ST-elevation myocardial infarction and multivessel coronary artery disease reduces adverse events compared to infarct-related artery only revascularization. Whether complete revascularization should be done as multivessel intervention during index procedure or as a staged procedure remains controversial. METHOD We performed a meta-analysis of randomized controlled trials comparing outcomes of multivessel intervention in patients with ST-elevation myocardial infarction and multivessel coronary artery disease as staged procedure versus at the time of index procedure. Composite of death or myocardial infarction was the primary outcome. Mantel-Haenszel risk ratios were calculated using random effect model. RESULTS Six randomized studies with a total of 1126 patients met our selection criteria. At a mean follow-up of 13 months, composite of myocardial infarction or death (7.2% vs 11.7%, RR: 1.66, 95%CI: 1.09-2.52, P = 0.02), all cause mortality (RR: 2.55, 95%CI: 1.42-4.58, P < 0.01), cardiovascular mortality (RR: 2.8, 95%CI: 1.33-5.86, P = 0.01), and short-term (<30 days) mortality (RR: 3.54, 95%CI: 1.51-8.29, P < 0.01) occurred less often in staged versus index procedure multivessel revascularization. There was no difference in major adverse cardiac events (RR: 1.14, 95%CI: 0.88-1.49, P = 0.33), repeat myocardial infarction (RR: 1.14, 95%CI: 0.68-1.92, P = 0.61), and repeat revascularization (RR: 0.92, 95%CI: 0.66-1.28, P = 0.62). CONCLUSION In patients with ST-elevation myocardial infarction and multivessel coronary artery disease, a strategy of complete revascularization as a staged procedure compared to index procedure revascularization results in reduced mortality without an increase in repeat myocardial infarction or need for repeat revascularization.

Predictors of short‐ and long‐term mortality in hospitalized veterans with elevated troponin

BACKGROUND Cardiac troponin elevation is associated with mortality. We compared the mortality risk related to elevated troponin from acute coronary syndrome (ACS) and non-ACS causes in a hospitalized elderly veteran population. METHODS AND RESULTS As part of a quality initiative at our Veterans Affairs hospital, all patients with elevated troponin were evaluated by a cardiologist to determine if ACS was present and to recommend management. We selected a sample (n = 761) of consecutive patients studied between February 2006 and February 2007 and examined all-cause mortality over extended follow-up. Nearly all were men (99.1%), and about half had coronary disease (n = 385, 50.5%) and diabetes (n = 339, 44.4%). ACS patients had lower mortality that non-ACS patients. Mortality began to diverge at 30 days; at 1 year it was 42.0% versus 29.0% (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.41-0.78) and at 6 years 77.7% versus 58.7% (OR: 0.41, 95% CI: 0.30-0.56). Cox regression models for mortality at multiple time points yielded several independent factors associated with mortality; however, the distribution of the factors was not sufficient to explain the observed difference in mortality. CONCLUSIONS In this elderly, male veteran population, mortality related to an elevated troponin was higher at 1 and 6 years for non-ACS patients compared with ACS patients. Factors independently associated with a higher mortality risk were predominantly markers of general systemic illness, but did not elucidate the reasons why troponin elevation secondary to non-ACS causes carries this higher risk. A better understanding of these cardiac troponin elevations and implications for future mortality requires additional investigation. Journal of Hospital Medicine 2016;11:773-777.

Meta-Analysis of Aspirin Versus Dual Antiplatelet Therapy Following Coronary Artery Bypass Grafting

Although aspirin monotherapy is considered the standard of care after coronary artery bypass grafting (CABG), more recent evidence has suggested a benefit with dual antiplatelet therapy (DAPT) after CABG. We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of aspirin monotherapy with DAPT in patients after CABG. Subgroup analyses were conducted according to surgical technique (i.e., on vs off pump) and clinical presentation (acute coronary syndrome vs no acute coronary syndrome). Random effects overall risk ratios (RR) were calculated using the DerSimonian and Laird model. Eight randomized control trials and 9 observational studies with a total of 11,135 patients were included. At a mean follow-up of 23 months, major adverse cardiac events (10.3% vs 12.1%, RR 0.84, confidence interval [CI] 0.71 to 0.99), all-cause mortality (5.7% vs 7.0%, RR 0.67, CI 0.48 to 0.94), and graft occlusion (11.3% vs 14.2%, RR 0.79, CI 0.63 to 0.98) were less with DAPT than with aspirin monotherapy. There was no difference in myocardial infarction, stroke, or major bleeding between the 2 groups. In conclusion, DAPT appears to be associated with a reduction in graft occlusion, major adverse cardiac events, and all-cause mortality, without significantly increasing major bleeding compared with aspirin monotherapy in patients undergoing CABG.

Transesophageal Echocardiography for the Detection of Patent Foramen Ovale

To the Editor: We read with interest the recent article by Yamashita et al. Given that an effective Valsalva maneuver can be difficult to perform with sedation during a transesophageal echo (TEE) bubble study, the authors investigated the diagnostic yield of TEE for the detection of patent foramen ovale (PFO) by comparing provocation maneuver with Valsalva versus inferior vena cava (IVC) compression. The study concluded that IVC compression yielded a higher detection of PFO compared with rest (P < .05) and was noninferior to the Valsalva maneuver (P =NS). We commend the authors for their work, but several factors should be considered when interpreting these results. The final results of the study were not compared to transthoracic echo (TTE), transcranial Doppler (TCD), or right heart catheterization for correlation. While TEE bubble study is considered by many as the reference standard for the detection of PFO, TEE can either miss or misdiagnose a PFO in 10% of patients when one relies on TEE alone. A recent meta-analysis of prospective studies determined that TEE bubble study has a sensitivity of 89% and specificity of 91% when compared to confirmation by autopsy, surgery, and/or right heart catheterization. The imperfect accuracy of TEE may be attributed to technical limitations including patient intolerance for the TEE probe, an inadequate Valsalva maneuver during sedation with a probe in the esophagus, variations in patient anatomy, and operator experience. While provocation with the IVC compression method may overcome the limitation with Valsalva, certain other modifications to the bubble study protocol may enhance the diagnostic yield of TEE for the detection of PFO. First, for patients who are unable to perform a sustained Valsalva maneuver, unloading the left ventricle with nitroglycerin may reverse the interatrial pressure gradient, promote leftward bulging of the interatrial septum, and reduce the number of false negative TEEs. Johansson et al. demonstrated that the sensitivity of TEE can be increased by using at least five contrast injections in an attempt to visualize both the leftward bulging of the interatrial septum and dense right atrial contrast filling adjacent to the septum. Furthermore, addition of the patient’s blood to the agitated saline mixture has been found to increase the sensitivity of bubble studies without compromising specificity when compared to agitated saline alone and other contrast agents. Bubble studies performed with echocardiography on harmonic imaging mode have a higher yield for the detection of PFO compared to fundamental imaging. Finally, if femoral venous access is present, femoral vein injection of echo contrast medium increases the sensitivity for the detection of PFO compared with brachial injection due to direct flow from the IVC toward the foramen ovale. Since a bubble study performed with TCD has a higher sensitivity for the detection of intracardiac right-to-left shunt compared to TTE or TEE, our preferred screening method is with a TCD followed by confirmation with TEE or intracardiac echo. However, TCD is limited by its inability to differentiate between a PFO, atrial septal defect, or transpulmonary shunt, providing no data on the shape and size of the defect. TEE has the added benefit of accurately visualizing the atrial septal anatomy, differentiating between an intracardiac and transpulmonary shunt, and assessing other etiologies of

Safety and efficacy of second-generation drug-eluting stents compared with bare-metal stents: An updated meta-analysis and regression of 9 randomized clinical trials

The efficacy of second‐generation drug‐eluting stents (DES; eg, everolimus and zotarolimus) compared with bare‐metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta‐analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second‐generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second‐generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second‐generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69‐0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48‐0.95), target‐lesion revascularization (RR: 0.47, 95% CI: 0.42‐0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41‐0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38‐0.80). The incidence of all‐cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79‐1.10). Meta‐regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P < 0.0001, respectively). Compared with BMS, second‐generation DES appear to be associated with a lower incidence of MACE, mainly driven by lower rates of target‐lesion revascularization, MI, and stent thrombosis. However, all‐cause mortality appears similar between groups.

Constrictive pericarditis from an endocardial pacemaker lead

Constrictive pericarditis secondary to endocardial pacemaker inflammation, without associated pericardial effusion or infection, has yet to be described in the literature. We present a case of a 42-year-old man who developed recurrent ascites from regional constrictive pericarditis following pacemaker implant. Symptoms resolved after pericardiectomy.

In-Hospital Outcomes of Transcatheter Aortic Valve Implantation in Patients With End-Stage Renal Disease on Dialysis from a Large National Database

The outcomes of patients with end-stage renal disease on dialysis (chronic kidney disease stage 5 on dialysis [CKD 5D]) who undergo transcatheter aortic valve implantation (TAVI) are not well described due to the exclusion of this group in randomized trials. We analyzed the National Inpatient Sample database and compared clinical characteristics and in-hospital outcomes for patients with CKD 5D versus those without CKD 5D (nondialysis group) who underwent TAVI in 2011 to 2014 in the United States. The study population included 1,708 patients (4%) with CKD 5D and 40,481 patients (96%) without CKD 5D who underwent TAVI. Patients with CKD 5D were younger (75.3 ± 9.9 vs 81.4 ± 8.4 years, p <0.001), more likely to be men (62.8% vs 52%, p <0.001), and less likely to be Caucasian (73.6% vs 87.8%, p <0.001). Patients with CKD 5D were more likely to have congestive heart failure (16% vs 11.7%, p <0.001), diabetes with chronic complications (19% vs 5.4%, p <0.001), hypertension (86.5% vs 79.3%, p <0.001), and peripheral vascular disease (34.5% vs 29.4%, p <0.001), but were less likely to have atrial fibrillation (38.6% vs 44.8%, p <0.001) and chronic pulmonary disease (27.5% vs 33.6%, p <0.001). In-hospital mortality was significantly higher in the dialysis group (8.2% vs 4%; adjusted odds ratio 2.21, 95% confidence interval1.81 to 2.69, p <0.001) after adjusting for age, gender, co-morbidities, and hospital characteristics in a robust multivariate regression model. In conclusion, patients with CKD 5D who undergo TAVI have a higher in-hospital mortality than those without CKD 5D.

Erythropoietin therapy after out-of-hospital cardiac arrest: A systematic review and meta-analysis

AIM To assess safety and efficacy of early erythropoietin (Epo) administration in patients with out-of-hospital cardiac arrest (OHCA). METHODS A systematic literature search was performed using PubMed, MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases, of all studies published from the inception through October 10, 2016. Inclusion criteria included: (1) Adult humans with OHCA and successful sustained return of spontaneous circulation; and (2) studies including mortality/brain death, acute thrombotic events as their end points. Primary efficacy outcome was “brain death or Cerebral Performance Category (CPC) score of 5”. Secondary outcomes were “CPC score 1, and 2-4”, “overall thrombotic events” and “acute coronary stent thrombosis”. RESULTS We analyzed a total of 606 participants (n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials. No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5 (OR = 0.77; 95%CI: 0.42-1.39), CPC score 1 (OR = 1.16, 95%CI: 0.82-1.64), and CPC score 2-4 (OR = 0.77, 95%CI: 0.44-1.36). Epo group was associated with increased thrombotic complications (OR = 2.41, 95%CI: 1.26-4.62) and acute coronary stent thrombosis (OR = 8.16, 95%CI: 1.39-47.99). No publication bias was observed. CONCLUSION Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.

Advancements in pharmacotherapy for angina

ABSTRACT Introduction: Angina pectoris is the most prevalent symptomatic manifestation of ischemic heart disease, frequently leads to a poor quality of life, and is a major cause of medical resource consumption. Since the early descriptions of nitrite and nitrate in the 19th century, there has been considerable advancement in the pharmacologic management of angina. Areas covered: Management of chronic angina is often challenging for clinicians. Despite introduction of several pharmacological agents in last few decades, a significant proportion of patients continue to experience symptoms (i.e., refractory angina) with subsequent disability. For the purpose of this review, we searched PubMed and Cochrane databases from inception to August 2016 for the most clinically relevant publications that guide current practice in angina therapy and its development. In this article, we briefly review the pathophysiology of angina and mechanism-based classification of current therapy. This is followed by evidence-based insight into the traditional and novel pharmacotherapeutic agents, highlighting their clinical usefulness. Expert opinion: Considering the wide array of available therapies with different mechanism efficacy and limiting factors, a personalized approach is essential, particularly for patients with refractory angina. Ongoing research with novel pharmacologic modalities is likely to provide new options for management of angina.