Metal pollutants and cardiovascular disease: mechanisms and consequences of exposure.

INTRODUCTION: There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, is a significant risk factor for CVD. METHODS: We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy (TACT) strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. CONCLUSIONS: There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor.

Minimally invasive mitral valve surgery expands the surgical options for high-risks patients.

BACKGROUND: A simplified minimally invasive mitral valve surgery (MIMVS) approach avoiding cross-clamping and cardioplegic myocardial arrest using a small (5 cm) right antero-lateral incision was developed. We hypothesized that, in high-risk patients and in patients with prior sternotomy, this approach would yield superior results compared to those predicted by the Society of Thoracic Surgeons (STS) algorithm for standard median sternotomy mitral valve surgery. METHODS: Five hundred and four consecutive patients (249 males/255 females), median age 65 years (range 20-92 years) underwent MIMVS between 1/06 and 8/09. Median preoperative New York Heart Association function class was 3 (range 1-4). Eighty-two (16%) patients had an ejection fraction ≤35%. Forty-seven (9%) had a STS predicted mortality ≥10%. Under cold fibrillatory arrest (median temperature 28°C) without aortic cross-clamp, mitral valve repair (224/504, 44%) or replacement (280/504, 56%) was performed. RESULTS: Thirty-day mortality for the entire cohort was 2.2% (11/504). In patients with a STS predicted mortality ≥ 10% (range 10%-67%), the observed 30-day mortality was 4% (2/47), lower than the mean STS predicted mortality of 20%. Morbidity in this high-risk group was equally low: 1 of 47 (2%) patients underwent reexploration for bleeding, 1 of 47 (2%) patients suffered a permanent neurologic deficit, none had wound infection. The median length of stay was 8 days (range 1-68 days). CONCLUSIONS: This study demonstrates that MIMVS without aortic cross-clamp is reproducible with low mortality and morbidity rates. This approach expands the surgical options for high-risk patients and yields to superior results than the conventional median sternotomy approach.

A Wasted Opportunity During a Pandemic: The Foreign Medical Graduates in the USA.

In this brief note from the field, we address an essential issue of non-inclusion of Foreign Medical Graduates (FMG) practicing in the US into the healthcare disaster response in the current pandemic. Because FMGs represent a significant share of the entire country's physician workforce, it seems not prudent to ignore the need to address the current immigration barriers affecting the crucial healthcare needs during this pandemic. Being subjects of the ongoing complex bureaucracy complicated by recent anti-immigrant steps, FMGs that practice for years on temporary (H1B) visas cannot fully join COVID-19 forces. In addition, these physicians face multiple challenges related to their health protection, protection of their immediate family, job security, and the potential risk of being deported. We believe that physicians' immigration status should no longer be disregarded outside of academic interest. It carries the same importance as other public health issues, especially in severe healthcare crises like this pandemic.

Among sepsis survivors, readmissions due to infections occur sooner and are associated with increased mortality.

BACKGROUND: Readmissions after sepsis hospitalisations are more likely to result in death compared to readmissions after non-sepsis hospitalisations. METHODS: Retrospective study of one hundred and forty-seven intensive care unit survivors of severe sepsis. RESULTS: Over a median follow-up of 565 (200-953) days, 88 patients (59.8%) were readmitted, 40 with an infectious process (45.4%) and 48 with a non-infectious condition (54.5%). Median time to first rehospitalisation for the entire cohort was 89 (19-337) days; patients admitted with an infectious cause were readmitted sooner; 65.7 (11-201) days vs. 144 (52.3-383) days, P = 0.02. Most cases of infectious readmissions were due to pneumonia (17 patients, 42.5%), and urinary tract infections (UTI) (7 patients, 17.5%). Survival rate was 45% (18/40) in those readmitted with an infectious process vs. 70.8% (34/48) in those readmitted due to a non-infectious cause, P = 0.01. In multivariate analyses, age (HR 1.04 [95% CI: 1.01-1.08]; P = 0.002) and infectious cause of readmission (HR 2.0 [95% CI: 1.005-4]; P = 0.04) remained associated with increased mortality. CONCLUSIONS: Among sepsis survivors, infections are associated with shorter time to hospital readmission and higher mortality vs non-infectious causes. Most of the infectious readmissions were due to pneumonia or UTI, which mirrored the index hospitalisations.

Idiopathic mitral valve disease in a patient presenting with Axenfeld-Rieger syndrome.

A 33-year-old, previously healthy male presented with respiratory distress and underwent intubation. A physical examination revealed a holosystolic murmur and pupillary abnormalities. Echocardiography revealed a flail anterior mitral valve leaflet with ruptured chordae and severe mitral regurgitation. The patient underwent urgent mitral valve replacement and tolerated the procedure well. The mitral valve leaflet was myxomatous and calcified -- an unusual find in such a patient. An ophthalmology consultation was obtained and the patient diagnosed with Axenfeld-Rieger syndrome, a disorder of the anterior ocular chamber that has been associated with cardiac malformations. The present case report adds to the body of literature which suggests a correlation between Axenfeld-Rieger syndrome and valvular abnormalities. Hence, it is believed prudent that patients with Axenfeld-Rieger syndrome should undergo echocardiographic screenings for valvular abnormalities.

Minimally invasive papillary muscle sling placement during mitral valve repair in patients with functional mitral regurgitation.

BACKGROUND: We evaluated the safety and feasibility of minimally invasive mitral valve repair with papillary muscle sling placement via a right anterior thoracotomy approach in patients with severe functional mitral regurgitation (MR). METHODS: We retrospectively reviewed all minimally invasive mitral valve repairs with papillary muscle sling placement in patients with severe functional MR performed at our institution between October 2011 and September 2012. The operative times, lengths of stay, postoperative complications, and mortality were analyzed. RESULTS: We identified a total of 19 consecutive patients. There were 12 men (63%); the mean age was 60 ± 13 years. The mean ± SD left ventricular ejection fraction was 23% ± 5.5%, and 4 (21%) of the patients underwent previous coronary artery bypass graft surgery. The median aortic cross-clamp and cardiopulmonary bypass times were 106 (interquartile range [IQR], 76-120) and 163 (IQR, 119-170) minutes, respectively. The median intensive care unit length of stay was 64 (IQR, 43-75) hours, and the median postoperative length of stay was 7 (IQR, 5-7.5) days. Postoperatively, 2 patients developed acute kidney injury. There were no reoperations for bleeding or any cerebrovascular accidents. The 30-day mortality was 0. A follow-up echocardiogram, obtained at a median of 3 (IQR, 1-7.5) months, demonstrated none to trivial MR in all patients. CONCLUSIONS: Minimally invasive mitral repair with papillary muscle sling placement for severe functional MR is safe and effective in the short-term. Long-term data are needed to evaluate the effects on left ventricular remodeling and to assess the durability of the repair.

Comparison of 30-day outcomes of coronary artery bypass grafting surgery verus hybrid coronary revascularization stratified by SYNTAX and euroSCORE.

OBJECTIVE: The optimal treatment of multivessel coronary artery disease is not well established. Hybrid coronary revascularization by combining the left internal mammary artery-left anterior descending artery graft and drug-eluting stents in non-left anterior descending artery territories might offer superior results compared with sole coronary artery bypass grafting or sole percutaneous coronary intervention. METHODS: We retrospectively analyzed the 30-day outcomes of 381 consecutive patients undergoing coronary artery bypass grafting (n = 301) vs hybrid coronary revascularization (n = 80). In a 2 × 2 matrix, the 2 groups were stratified by the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (≤32 vs ≥33) and the European System for Cardiac Operative Risk Evaluation (euroSCORE) (<5 vs ≥5). The composite endpoint (death from any cause, stroke, myocardial infarction, low cardiac output syndrome) and secondary endpoints (worsening postprocedural renal function and bleeding) were determined. RESULTS: After stratification using the SYNTAX and the euroSCORE, the preoperative characteristics were similar within the 4 groups, except for the ≥33 SYNTAX/>5 euroSCORE. The hybrid coronary revascularization patients were older (77 vs 65 years, P = .001). The postoperative outcomes using combined SYNTAX and the euroSCORE stratification showed a similar rate of the composite endpoint for all groups except for patients with ≥33 SYNTAX/>5 euroSCORE (0% for the coronary artery bypass grafting group vs 33% for the hybrid coronary revascularization group, P = .001). An analysis of the secondary endpoint showed similar results across all groups, except for in the ≥33 SYNTAX/>5 euroSCORE group, in which bleeding (re-exploration for bleeding and transfusion >3 packed red blood cell units per patient) was 44% in the hybrid coronary revascularization group vs 11% in the coronary artery bypass grafting group (P = .05). CONCLUSIONS: Hybrid coronary revascularization is a safe alternative to coronary artery bypass grafting in many patients with multivessel coronary artery disease. However, in high-risk patients with complex coronary artery disease (≥33 SYNTAX/>5 euroSCORE), coronary artery bypass grafting is superior to hybrid coronary revascularization.

Benefits of ambulatory axillary intra-aortic balloon pump for circulatory support as bridge to heart transplant.

OBJECTIVE: Axillary intra-aortic balloon pump therapy has been described as a bridge to transplant. Advantages over femoral intra-aortic balloon pump therapy include reduced incidence of infection and enhanced patient mobility. We identified the patients who would benefit most from this therapy while awaiting heart transplantation. METHODS: We conducted a single-center, retrospective observational study to evaluate outcomes from axillary intra-aortic balloon pump therapy. These included hemodynamic parameters, duration of support, and success in bridging to transplant. We selected patients on the basis of history of sternotomy, elevated panel-reactive antibody, and small body habitus. Patients were made to ambulate aggressively beginning on postoperative day 1. RESULTS: Between September 2007 and September 2010, 18 patients underwent axillary intra-aortic balloon pump therapy. All patients had the devices placed through the left axillary artery with a Hemashield side graft (Boston Scientific, Natick, Mass). Before axillary placement, patients underwent femoral placement to demonstrate hemodynamic benefit. Duration of support ranged from 5 to 63 days (median = 19 days). There was marked improvement in ambulatory potential and hemodynamic parameters, with minimal blood transfusion requirements. There were no device-related infections. Some 72% of the patients (13/18) were successfully bridged to transplantation. CONCLUSIONS: Axillary intra-aortic balloon pump therapy provides excellent support for selected patients as a bridge to transplant. The majority of the patients were successfully bridged to transplant and discharged. Although this therapy has been described in previous studies, this is the largest series to incorporate a regimen of aggressive ambulation with daily measurements of distances walked.

Improved midterm outcomes for type A (central) pulmonary emboli treated surgically.

OBJECTIVES: We propose a simplified anatomic classification for pulmonary emboli that algorithmically differentiates those who might be best treated with surgical pulmonary embolectomy (type A) from those best treated medically (type B). We hypothesized that patients with type A pulmonary emboli treated with immediate surgical embolectomy demonstrate superior long-term survival compared with patients with type A pulmonary emboli treated medically. METHODS: Patients admitted between 2002 and 2008 with a diagnosis of pulmonary emboli made based on computed tomographic angiographic imaging (n = 779) were analyzed. Computed tomographic angiographic images were reviewed in a blind fashion, and anatomic classification of emboli was made. Patients with central thrombus, defined by location medial to the lateral mediastinal boundaries (ie, involving the main, primary, or both branch pulmonary arteries), were classified as having type A pulmonary emboli (n = 107), whereas those with peripheral pulmonary emboli located beyond these boundaries were classified as having type B pulmonary emboli (n = 672). Four patients with type A pulmonary emboli treated with catheter embolectomy were excluded from the analysis. RESULTS: Of the 103 patients with type A pulmonary emboli, 15 (14%) were treated with immediate surgical pulmonary embolectomy, and 88 (85%) were treated medically. Patients with type A pulmonary emboli treated surgically had similar 30-day mortality compared with those treated medically (13% vs 17%, P = .532). At a mean of 24 ± 18 months' follow-up (range, 1-82 months), survival at 1, 3, and 5 years for patients with type A pulmonary emboli treated surgically was significantly better than that in the patients with type A pulmonary emboli treated medically (P = .0001). CONCLUSIONS: For patients with type A pulmonary emboli, immediate surgical intervention appears to offer superior midterm survival compared with medical treatment alone. Although the medical and surgical groups were substantially different and the differences might have affected survival, this simplified classification for pulmonary emboli might help direct optimal treatment strategies.

Current status of hybrid coronary revascularization.

Hybrid coronary revascularization combines coronary artery bypass surgery with percutaneous coronary intervention techniques to treat coronary artery disease. The potential benefits of such a technique are to offer the patients the best available treatments for coronary artery disease while minimizing the risks of the surgery. Hybrid coronary revascularization has resulted in the establishment of new 'hybrid operating suites', which incorporate and integrate the capabilities of a cardiac surgery operating room with that of an interventional cardiology laboratory. Hybrid coronary revascularization has greatly augmented teamwork and cooperation between both fields and has demonstrated encouraging as well as good initial outcomes.

Results of completion arteriography after minimally invasive off-pump coronary artery bypass.

BACKGROUND: The benefits of a minimally invasive approach to off-pump coronary artery bypass remain controversial. The value of completion arteriography in validating this technique has not been investigated. METHODS: From April 2007 to October 2009, fifty-six patients underwent isolated minimally invasive coronary artery bypass grafting through a left thoracotomy without cardiopulmonary bypass. Forty-three of these patients underwent completion arteriography. RESULTS: Sixty-five grafts were performed in these 56 patients, (average, 1.2 grafts per patient; range, 1 to 3). Forty-eight grafts were studied in the 43 patients undergoing completion arteriography. There were 4 findings on arteriogram leading to further immediate intervention (8.3%). These included 3 grafts with anastomotic stenoses or spasm requiring stent placement, and 1 patient who had limited dissection in the left internal mammary artery graft and underwent placement of an additional vein graft. These findings were independent of electrocardiographic changes or hemodynamic instability. The remainder of the studies showed no significant abnormalities. There were no deaths. One patient who did not have a completion arteriogram suffered a postoperative myocardial infarction requiring stent placement for anastomotic stenosis. Patients were discharged home an average of 6.8 days postoperatively. There were no instances of renal dysfunction postoperatively attributable to catheterization. CONCLUSIONS: Minimally invasive coronary artery bypass is safe and effective. Findings of completion arteriography occasionally reveal previously under-recognized findings that, if corrected in a timely fashion, could potentially impact graft patency and clinical outcomes. Our experience validates this minimally invasive technique.

The new era of cardiac surgery: hybrid therapy for cardiovascular disease.

Surgical therapy for cardiovascular disease carries excellent long-term outcomes but it is relatively invasive. With the development of new devices and techniques, modern cardiovascular surgery is trending toward less invasive approaches, especially for patients at high risk for traditional open heart surgery. A hybrid strategy combines traditional surgical treatments performed in the operating room with treatments traditionally available only in the catheterization laboratory with the goal of offering patients the best available therapy for any set of cardiovascular diseases. Examples of hybrid procedures include hybrid coronary artery bypass grafting, hybrid valve surgery and percutaneous coronary intervention, hybrid endocardial and epicardial atrial fibrillation procedures, and hybrid coronary artery bypass grafting/carotid artery stenting. This multidisciplinary approach requires strong collaboration between cardiac surgeons, vascular surgeons, and interventional cardiologists to obtain optimal patient outcomes.

The delta-opioid receptor agonist DADLE at reperfusion protects the heart through activation of pro-survival kinases via EGF receptor transactivation.

The specific delta-opioid receptor agonist [D-Ala(2)-D-Leu(5)]enkephalin (DADLE) protects against infarction in the heart when given before ischemia. In rabbit, this protection leads to phosphorylation of the pro-survival kinases Akt and extracellular signal-regulated kinase (ERK) and is dependent on transactivation of the epidermal growth factor receptor (EGFR). DADLE reportedly protects rat hearts at reperfusion. We therefore tested whether DADLE at reperfusion could protect isolated rabbit hearts subjected to 30 min of regional ischemia and 120 min of reperfusion and whether this protection is dependent on Akt, ERK, and EGFR. DADLE (40 nM) was infused for 1 h starting 5 min before reperfusion and reduced infarct size from 31.0 +/- 2.3% in the control group to 14.6 +/- 1.6% (P = 0.01). This protection was abolished by cotreatment of the metalloproteinase inhibitor (MPI) and the EGFR inhibitor AG1478. In contrast, 20 nM DADLE, although known to be protective before ischemia, failed to protect. Western blotting revealed that DADLE's protection was correlated to increase in phosphorylation of the kinases Akt and ERK1 and -2 in reperfused hearts (2.5 +/- 0.5, 1.6 +/- 0.2, and 2.3 +/- 0.7-fold of baseline levels, P < 0.05 vs. control). The DADLE-dependent increases in Akt and ERK1/2 phosphorylation were abolished by either MPI or AG1478, confirming a signaling through the EGFR pathway. Additionally, DADLE treatment increased phosphorylation of EGFR (1.4 +/- 0.2-fold, P = 0.03 vs. control). Thus the delta-opioid agonist DADLE protects rabbit hearts at reperfusion through activation of the pro-survival kinases Akt and ERK and is dependent on the transactivation of the EGFR.

NECA at reperfusion limits infarction and inhibits formation of the mitochondrial permeability transition pore by activating p70S6 kinase.

The A1/A2 adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) limits infarction when administered at reperfusion. The present study investigated whether p70S6 kinase is involved in this anti-infarct effect. Adult rat ventricular myocytes were isolated and incubated in tetramethylrhodamine ethyl ester (TMRE, 100 nM), which causes cells to fluoresce in proportion to their mitochondrial membrane potential. A reduction in TMRE fluorescence serves as an indicator of collapse of the mitochondrial transmembrane potential. Cells were subjected to H2O2 (200 microM), which like ischemia induces loss of mitochondrial membrane potential. Fluorescence was measured every 3 min and to facilitate quantification membrane potential was arbitrarily considered as collapsed when fluorescence reached less than 60% of the starting value. Adding NECA (1 mM) to the cells prolonged the time to fluorescence loss (48.0+/-3.2 min in the NECA group versus 29.5+/-2.2 min in untreated cells, P<0.001) and the mTOR/p70S6 kinase inhibitor rapamycin (5 nM) abolished this protection (31.3+/-3.4 min). Since cyclosporine A offered similar protection, mitochondrial permeability transition pore formation is a likely cause of the H2O2-induced loss of potential. The direct GSK-3beta inhibitor SB216763 (3 microM) also prolonged the time to fluorescence loss (49.2+/-2.1 min, P<0.001 versus control), and its protection could not be blocked by rapamycin (42.2+/-2.3 min, P<0.001 versus control). NECA treatment (100 nM) of intact isolated rabbit hearts at reperfusion after 30 min of regional ischemia decreased infarct size from 33.0+/-3.8% of the risk zone in control hearts to 11.8+/-2.0% (P<0.001), and rapamycin blocked this NECA-induced protection (38.3+/-3.7%). A comparable protective effect was seen for SB216763 (1 microM) with infarct size reduction to 13.5+/-2.3% (P<0.001). NECA treatment (200 nM) of intact rabbit hearts at reperfusion also resulted in phosphorylation of p70S6 kinase more than that seen in untreated hearts. This NECA-induced phosphorylation was blocked by rapamycin. These experiments reveal a critical role for p70S6 kinase in the signaling pathway of NECA's cardioprotection at reperfusion.