Therapeutic Advances in Cardiovascular Disease

Assessment of both short- and long-term outcomes in patients undergoing off-pump coronary artery bypass using a perioperative metabolic protocol.

A total of 975 of 995 adult patients underwent coronary artery bypass ‘off-pump’ from 1997 through 2006. Patients presenting in cardiogenic shock were excluded from this assessment. A perioperative metabolic protocol, which included the implementation of allopurinol, insulin supplementation, magnesium sulfate, supplemental corticosteroids, milrinone, norepinephrine (prn), aspirin, clopidogrel, statins and β-blockers, was used in these patients.

The mean age at the time of surgery was 70.5 years and the average number of bypass grafts was 4 per procedure; 18% (n = 176) of the cases had a preoperative intra-aortic balloon pump inserted for hemodynamic instability, tight left main coronary artery stenosis or angina. The 30-day mortality was 1.8% versus a Society of Thoracic Surgeons (STS) predicted mortality of 4.8%. Left main coronary artery disease was present in 38% (n = 371) of the patients. No strokes occurred intra-operatively and the postoperative incidence of stroke was 0.9% (n = 9). Incidence of renal failure requiring dialysis was 0.8% (n = 8). There was a single sternal infection. Mean follow up was 65 months with a survival rate of 90% (n = 955). Re-intervention, which commonly involved PTCA ± stent placement or re-do coronary artery bypass grafting (CABG), was 4% at 1 year and 11.6% (n = 113) during the 65-month follow-up period.

Off-pump coronary artery bypass coupled with this novel metabolic protocol was associated with a low operative mortality and acceptable perioperative morbidities, including patients with left main coronary artery disease. These benefits are apparent at both short- and medium-term follow up.

Recent evidence has shown that, in heart failure (HF), clinically relevant concentrations of angiotensin-(1-7) [Ang-(1-7)] counteracts angiotensin II induced cardiac depression and produces positive inotropic effects in both left ventricle (LV) and myocytes. However, the underlying electrophysiological mechanism is unclear. We investigated the role and mechanism of Ang-(1-7) on LV myocyte L-type calcium current (I_Ca,L) responses in normal state and in HF.

We compared the effect of Ang-(1-7) (10⁻⁵ M) on I_Ca,L responses in isolated LV myocytes obtained from 11 rats with isoproterenol (ISO) induced HF (3 months after 170 mg/kg subcutaneous for 2 days) and from 8 age-matched normal control rats by patch clamp technique.

In normal myocytes, compared with baseline, superfusion of Ang-(1-7) caused no significant changes in I_Ca,L (8.2 ± 0.2 versus 8.0 ± 0.3 pA/pF, p= not significant). In HF myocytes, the baseline I_Ca,L was significantly reduced (5.3 ± 0.1 versus 8.0 ± 0.3 pA/pF, p < 0.01). Ang-(1-7) produced a 21% increase in I_Ca,L (6.4±0.1 versus 5.3±0.1 pA/pF, p < 0.01). Pretreatment of HF myocytes with a nitric oxide (NO) synthase inhibitor (L-NAME, 10⁻⁵ M) resulted in a significantly greater increase in I_Ca,L (28%, 8.4 ± 0.1 versus 6.5 ± 0.1 pA/pF, p < 0.01) during Ang-(1-7) superfusion. In contrast, during incubation with the bradykinin (BK) inhibitor HOE 140 (10⁻⁶ M), Ang-(1-7) induced increase in I_Ca,L was significantly decreased. The Ang-(1-7) induced increase in I_Ca,L was abolished by [D-Ala⁷]-Ang-(1-7) (A-779, 10⁻⁵ M).

HF alters the response of I_Ca,L to Ang-(1-7). In normal myocytes, Ang-(1-7) has no significant effect on I_Ca,L. However, in HF myocytes, Ang-(1-7) increases I_Ca,L. These effects are mediated by the Ang-(1-7) Mas receptors and involve activation of NO/BK pathways.

Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study.

Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, min–max: 35–74 years old; 49.5% women) from the Gutenberg Health Study as well as in a subgroup of 3223 subjects (61.1% women, mean age 49.2, min–max 35–74 years old) without risk factors or self-reported cardiovascular disease. Age- and gender-adjusted mean values for viscosity were defined. Regression models showed a relationship between classical risk factors and blood viscosity measures; the overall R² of the multiple linear regression model was however as low as 0.067 and 0.049 for high and low shear stress viscosity, respectively. After correction for cardiovascular risk factors, there was a very mild association between viscosity and prevalent coronary artery disease and heart failure. Systolic, mean and diastolic blood pressure increased with increasing blood viscosity after correction for age and gender.

We provide reference values for viscosity in a population-based cohort. Blood viscosity decreases in older subjects and shows a very mild association with cardiovascular risk factors and prevalent disease in our cohort. There is a linear positive association between viscosity and blood pressure.

Small, observational trials have suggested a reduction in adjacent gastric activity with ingestion of soda water in myocardial perfusion imaging (MPI). We report our findings prior to and after implementation of soda water in 467 consecutive MPI studies.

Consecutive MPI studies performed at a high-volume facility referred for vasodilator (VD) or exercise treadmill testing (ETT) were retrospectively reviewed before and after implementation of the soda water protocol. Patients undergoing the soda water protocol received 100 ml of soda water administered 30 min prior to image acquisition and after stress. Studies were performed using a same day rest/stress protocol. Incidence of adjacent gastric activity, diaphragmatic attenuation, stress and rest perfusion defects, and major adverse cardiovascular events (MACE) outcomes defined as death, myocardial infarction, stroke, reevaluation for chest pain, and late revascularization (>90 days from MPI) were abstracted using International Classification of Diseases, Ninth Revision (ICD-9) search.

Two hundred and eighteen studies were performed prior to implementation of the soda water protocol and 249 studies were performed with the use of soda water. Baseline demographic data were equal between the groups with the exception of more patients undergoing VD stress receiving soda water (p < 0.001). Soda water was not associated with a decreased incidence of adjacent gastric activity with stress (54.7% versus 61.9% with no soda water, p = 0.129) or rest (68.6% versus 69.5% with no soda water, p = 0.919) imaging. Less adjacent gastric activity was observed with patients undergoing ETT who received soda water (42.5% versus 56.9% with no soda water, p = 0.031), but no difference was observed between the groups with VD stress (69.0% versus 68.1% with no soda water, p = 1.000).

The use of soda water prior to technetium-99m MPI was associated with lower rates of adjacent gastric activity only in patients undergoing ETT stress but not rest or VD stress. This differs from previously published data.

There is a great potential for nitric oxide (NO) eluting biomaterials in biomedical applications. These include the development of cardiovascular implants, wound healing products, or applications in cancer and respiratory therapy. While the potential of these materials as a therapy is becoming clearer, the real-time monitoring of NO is not easy and the success in the development of such materials depends on the accurate quantification of NO release.

To emphasize on the importance of a measurement technique on the outcome of an experiment, we compared total NO released from S-nitroso-N-acetyl-d-penicillamine (SNAP) incorporated nanocomposite polymer in the form of bypass grafts under simulated physiological conditions using amperometric and chemiluminescence techniques.

We found that the total amount of NO measured by the amperometric technique was 35.8% of the theoretical amount. Similarly, on measuring NO release from the bypass grafts, we demonstrated that the chemiluminesence technique detected NO at a relatively higher level.

The results of this study clearly demonstrate the relative difference between analysis techniques for accurate NO detection that can be applied to distinct experimental models associated with NO-eluting cardiovascular implants.

Coronary angioplasty in advanced age is associated with higher rate of comorbidities and complications. Drug coated balloon only angioplasty (DCBA) has emerged as an alternative to treat small vessel coronary disease (SVCD), of reference vessel diameters <2.8 mm, with shorter duration of dual antiplatelet (DAPT). This is the first study to assess the DCBA efficacy in an elderly population with SVCD.

We performed a prospective study of 447 patients (334 patients aged <75 and 113 patients aged ⩾75 years old) acquired from the SeQuent Please Small Vessel ‘Paclitaxel-Coated Balloon Only’ registry. In the older age group, more patients have hypertension (89% versus 77%; p = 0.006), renal insufficiency (21% versus 6%; p < 0.001), atrial fibrillation (17% versus 7%; p = 0.001), and calcified lesions (33% versus 20%; p = 0.006). At 30 days, there was one myocardial infarction requiring target lesion revascularization (TLR) in the younger group. No major adverse cardiac event (MACE) was observed in the older group. At 9 months, the MACE rate in the younger group was 4.2% and 6.1% in the older group (p = 0.453), with TLR rates at 3.9% and 3.0% (p = 0.704) respectively. There was no cardiac death observed.

DBCA in the elderly with SVCD is as safe and effective compared with younger patients despite more complex anatomy and comorbidities.

The aim of this study was to compare the two different directions of tumescent solution delivery (from distal to proximal knee to the saphenofemoral junction [SFJ] or proximal to distal SFJ to the knee) in terms of differences in tumescent volume, number of punctures, and pain and comfort scores of patients.

A total of 100 patients were treated with endovenous laser ablation (EVLA) under local anesthesia between August 2013 and October 2013. These 100 patients were divided into two groups. In group 1, tumescent solution was delivered in a proximal to distal direction. In group 2, the tumescent solution was delivered in a distal to proximal direction. In each group, the great saphenous vein (GSV) diameter, delivered total energy, treated GSV length, delivered tumescent volume, number of punctures, and pain and comfort scores were recorded for each patient.

All patients were treated unilaterally. EVLA was performed with 100% technical success in all patients. There was no difference statistically between group 1 and group 2 according to GSV diameter, delivered total energy, and treated GSV length. Average tumescent volume, number of punctures, and pain scores in group 2 were lower than in group 1 (p = 0.0001; p < 0.05). Also, the average comfort score was higher in group 2 than in group 1 (p = 0.0001; p < 0.05).

We believe that delivering the tumescent solution in a distal to proximal direction increases the comfort of both patient and surgeon with lower tumescent volume during the EVLA of the GSV.