Effect of the COVID-19 pandemic on ST-elevation myocardial infarction presentation and survival.

Presentation and outcomes of patients with ST-elevation myocardial infarction (STEMI) may change during viral pandemics. We compared symptom-tocall (STC), call-to-balloon (CTB), doorto-balloon (DTB) times; high-sensitivity troponin (hs-cTnI) levels; and survival of patients (n=39) during the first wave of the COVID-19 pandemic (defined as a 'COVID period' starting four weeks before lockdown) to historical controls from a 'pre-COVID period' (n=45). STEMI admissions fell one week before lockdown by 29%. Median STC times began to rise one month before lockdown (54 vs. 25 min, p=0.06), with peak increases between 9 March and 5 April (166 vs. 59 min, p=0.04). Median CTB and DTB times were unchanged. Mean peak hs-cTnI increased during COVID-19 (15,225 vs. 8,852 ng/ml, p=0.004). Six-month survival following all STEMI reduced (82.1% vs. 95.6%, p<0.05). STC times are the earliest indicator that STEMI-patient behaviour changed four weeks before lockdown, correlating with higher troponin levels and reduced survival. These early signals could guide public health interventions during future pandemics.

Yoga-Based Cardiac Rehabilitation: Current Perspectives from Randomized Controlled Trials in Coronary Artery Disease.

Coronary artery disease carries a high morbidity and mortality worldwide, and exercise-based cardiac rehabilitation programmes play a large role in secondary prevention. Exercise-based rehabilitation programmes are expensive, and in certain subgroups uptake is poor. Yoga has been suggested to show improvements in cardiovascular health which would support its use in cardiac rehabilitation programmes. We carried out a review of current randomized controlled trials to determine if yoga-based cardiac rehabilitation leads to reduced cardiac risk factors, and improved physiological and psychological outcomes in patients with coronary artery disease compared to standard care. Six randomized controlled studies were identified after a medical database search, and meta-analysis was carried out for the different outcomes. Overall, the addition of yoga to standard care resulted in improved subjective feeling of cardiac health and quality of life. There was also a trend towards improvement in left ventricular systolic function. Improvement in cardiac risk factors, MACE and psychological health in this cohort has still to be proven, but was not inferior to standard or enhanced care, and the benefits became more pronounced at longer follow-up. Future studies with longer follow-up and larger patient numbers would aid in accurately assessing the long-term benefit of yoga-based rehabilitation.

Changing paradigm for treatment of heavily calcified coronary artery disease. A complementary role of rotational atherectomy and intravascular lithotripsy with shockwave balloon: a case report.

BACKGROUND: Management of heavily calcified coronary arteries is still a major challenge in interventional cardiology. Inadequate stent expansion in calcific lesions is the single most important predictor of stent thrombosis and in-stent restenosis. Rotational atherectomy (RA) is an important tool to modify the calcium burden but is associated with limitations and requires specific skills. Intravascular lithotripsy (IVL) is a novel technique to treat calcified stenotic lesions and has been proposed as an alternative to RA with promising results. CASE SUMMARY: We report a case of a patient with severely calcified right coronary artery stenosis successfully treated with combination of RA and IVL. DISCUSSION: In this case, we demonstrate that the RA and IVL are complementary strategies, not sufficient on their own and not alternative to each other.

Percutaneous Retrieval of an Entrapped Rotational Atherectomy Burr Using Novel Technique of Controlled Traction and Counter Traction.

Burr entrapment is a rare but serious complication during rotational atherectomy (RA). The Japanese have termed this the Kokeshi phenomenon named after a wooden doll found in northern Japan consisted of a simple trunk but a large head akin to the Rotablator (Mechery et al., 2016; Kaneda et al., 2000). The reason underlying this complication is the lack of diamond dust on the back end of the burr (Lin et al., 2013). The burr is olive-shaped and has diamond coating at its distal surface for antegrade ablation. The proximal part is smooth without diamonds, which prevents backward ablation of tissues when retracted (Lin et al., 2013; Dahdouh et al., 2013). Rota entrapment usually needs surgical management with coronary artery bypass grafting (CABG) surgery. To date, only few cases of successful non-traumatic retrieval using nonsurgical bailout techniques have been published (Grise et al., 2002). We report a case of burr entrapment within the left anterior descending (LAD) artery which was successfully retrieved by combination of multiple maneuvers and the patient underwent routine PCI following the retrieval.

Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiological evidence.

BACKGROUND: NO is a major regulator of cardiovascular physiology that reduces vascular and cardiac contractility. Accumulating evidence indicates that endogenous inhibitors may regulate NOS. The NOS inhibitors asymmetric dimethylarginine (ADMA) and N-monomethylarginine are metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). This study was designed to determine if increased expression of DDAH could reduce tissue and plasma levels of the NOS inhibitors and thereby increase NO synthesis. METHODS AND RESULTS: We used gene transfer and transgenic approaches to overexpress human DDAH I in vitro and in vivo. The overexpression of DDAH in cultured endothelial cells in vitro induced a 2-fold increase in NOS activity and NO production. In the hDDAH-1 transgenic mice, we observed approximately 2-fold increases in tissue NOS activity and urinary nitrogen oxides, associated with a 2-fold reduction in plasma ADMA. The systolic blood pressure of transgenic mice was 13 mm Hg lower than that of wild-type controls (P<0.05). The systemic vascular resistance and cardiac contractility were decreased in response to the increase in NO production. CONCLUSIONS: DDAH I overexpression increases NOS activity in vitro and in vivo. The hDDAH-1 transgenic animal exhibits a reduced systolic blood pressure, systemic vascular resistance, and cardiac stroke volume. This study provides compelling evidence that the elaboration and metabolism of endogenous ADMA plays an important role in regulation of NOS activity.

Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase.

OBJECTIVE: Plasma levels of an endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA), are elevated in chronic renal failure, hypertension, and chronic heart failure. In patients with renal failure, plasma ADMA levels are an independent correlate of left ventricular ejection fraction. However, the cardiovascular effects of a systemic increase in ADMA in humans are not known. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled study in 12 healthy male volunteers, we compared the effects of intravenous low-dose ADMA and placebo on heart rate, blood pressure, cardiac output, and systemic vascular resistance at rest and during exercise. We also tested the hypothesis that ADMA is metabolized in humans in vivo by dimethylarginine dimethylaminohydrolase (DDAH) enzymes. Low-dose ADMA reduced heart rate by 9.2+/-1.4% from 58.9+/-2.0 bpm (P<0.001) and cardiac output by 14.8+/-1.2% from 4.4+/-0.3 L/min (P<0.001). ADMA also increased mean blood pressure by 6.0+/-1.2% from 88.6+/-3.4 mm Hg (P<0.005) and SVR by 23.7+/-2.1% from 1639.0+/-91.6 dyne. s. cm-5 (P<0.001). Handgrip exercise increased cardiac output in control subjects by 96.8+/-23.3%, but in subjects given ADMA, cardiac output increased by only 35.3+/-10.6% (P<0.05). DDAHs metabolize ADMA to citrulline and dimethylamine. Urinary dimethylamine to creatinine ratios significantly increased from 1.26+/-0.32 to 2.73+/-0.59 after ADMA injection (P<0.01). We estimate that humans generate approximately 300 micromol of ADMA per day, of which approximately 250 micromol is metabolized by DDAHs. CONCLUSIONS: This study defines the cardiovascular effects of a systemic increase in ADMA in humans. These are similar to changes seen in diseases associated with ADMA accumulation. Finally, our data also indicate that ADMA is metabolized by DDAHs extensively in humans in vivo.

all-trans-Retinoic acid increases nitric oxide synthesis by endothelial cells: a role for the induction of dimethylarginine dimethylaminohydrolase.

all-trans-Retinoic acid (atRA) has important effects on the developing and mature cardiovascular system. Nitric oxide (NO) production has been associated with the atRA-induced differentiation of neuronal cells, and we hypothesized that NO may also mediate certain actions of atRA in the cardiovascular system. We studied the effects of atRA on NO production by endothelial cells and determined whether regulation of enzymes responsible for metabolism of asymmetric dimethylarginine (ADMA) contributed to the effects seen. Murine endothelioma (sEnd.1) cells were incubated with or without atRA. Nitrite production was determined using the Griess reaction. The expression of NO synthase (NOS) and dimethylarginine dimethylaminohydrolase (DDAH) genes was determined by Northern blotting. A reporter gene assay was also used to study the effect of atRA on the DDAH II promoter. atRA significantly increased nitrite production by sEnd.1 cells despite no increase in eNOS expression. atRA also increased DDAH II gene expression and promoter activity and reduced the ratio of ADMA to symmetric dimethylarginine (SDMA) in culture medium. The DDAH inhibitor 4124W significantly reduced the induction of NO synthesis by atRA. The present study demonstrates that atRA increases NO synthesis in endothelial cells without increasing eNOS expression. atRA also increases the expression of DDAH II, the predominant DDAH isoform in endothelial cells. Our data suggests that the induction of NO synthesis by atRA may be facilitated by DDAH II. This pathway may help to explain some of the effects of atRA on the cardiovascular system.