1 year follow Up results of “ARTIM HF TRIAL” (angiotensin receptor neprilysin inhibitor effect on TEI index & left ventricular mass in heart failure)

BackgroundSacubitril/Valsartan (ARNI) has now class 1 recommendation for treatment of heart failure with reduced ejection fraction (HFrEF). It has been shown to reduce cardiovascular morbidity & mortality in Heart failure with reduced ejection fraction (HFrEF) and significant improvement in all echocardiographic parameters besides TEI index. Tei index is a marker of inflammation, myocardial cell metabolism and its contractile function has not been evaluated as a distinctive entity so we took up this study to evaluate the effects of ARNI on the LV functions using two dimensional (2D)ECHO parameters in Indian population and to assess TEI index for myocardial function.Methods256 patients with class II, III or IV HF and EF<40% were enrolled. 171(66.8%) were males and 85(33.2%) were females. Patients were evaluated at baseline, 6 and 12 months for LVEF, LV mass &,LVMPI. Drug was discontinued in 2 patients due to angioedema, in 5 patients due to acute kidney injury and in 2 patients due to hypotension. LV mass measurement done by linear echocardiographic method and Flow Doppler method used for TEI index calculation.ResultsBaseline parameters in 247 patients were mean EF = 26.33 ± 6.28%, mean LV mass = 270.84 ± 68.94 gm, mean Tei Index = 0.852 ± 0.22. ARNI use was associated with an average gradual increase in EF, from a mean baseline of 26.33 ± 6.28% to 33.88 ± 7.73%(p = 0.000001) after 1 year of treatment. There was a significant progressive reduction of 57.97 g/m2 in mean LV mass index after 1 year of treatment (p = 0.000001).TEI index showed significant reduction from baseline mean 0.85 ± 0.22 to 0.70 ± 0.12(p = 0.000001)after 1 year of treatment.ConclusionUse of ARNI as additive adjunct to standard care of treatment resulted in significant progressive decline in LV mass and increase in TEI index.     

Dynamic changes in injured myocardium,very early after acute myocardial infarction,quantified using T1 mapping cardiovascular magnetic resonance

Background

It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI.

Methods

A first group (n?=?31) underwent 3 acute 3?T CMR scans (time-point (TP) <?3?h, 24?h and 6?days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n?=?17) had a single scan at 24?h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping.

Results

The mean T1 relaxation time value within the AAR of the first group was reduced after 24?h (P?<?0.001 for TP1 vs.TP2) and subsequently increased at 6?days (P?=?0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P?=?1.0) but was between TP2 &TP3 (P?=?0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42?±?15% vs. 39?±?15%, P?=?0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion.

Conclusion

The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

     

Comparison of the efficacy of liraglutide with pioglitazone on dexamethasone induced hepatic steatosis,dyslipidemia and hyperglycaemia in albino rats

Objectives:To evaluate the efficacy of liraglutide with pioglitazone for prevention of dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycemia in Albino rats.Results:Dexamethasone caused hepatomegaly, dyslipidemia, and hyperglycemia. Both pioglitazone and liraglutide significantly reduced hepatomegaly, dyslipidemia and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone when compared with liraglutide (P < 0.01).Conclusion:Liraglutide has comparable efficacy to pioglitazone in prevention of dexamethasone induced hepatomegaly, dyslipidemia and fasting hyperglycemia.KEY WORDS: Dexamethasone, hepatomegaly, hyperglycemia, liraglutide, pioglitazone, prevention     

Ag2O nanoparticle-catalyzed substrate-controlled regioselectivities: direct access to 3-ylidenephthalides and isocoumarins

Herein, we disclose the first example of an efficient, silver oxide nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides 11–16 and isocoumarins 17–20via sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively. This one pot coupling involves reaction of substituted 2-halobenzoic acid with meta/para-substituted and ortho-substituted terminal alkynes, which proceeded in a regioselective manner resulting in the formation of 3-ylidenephthalides or isocoumarins, respectively, in excellent yields (up to 95%) with complete Z-selectivity. This protocol features relatively broad substrate scope, mild conditions, operational simplicity, and is favourable with aromatic/alicyclic terminal alkynes. The competition experiments and gram-scale synthesis further highlight the importance and versatility of the methodology. The proposed mechanistic pathways illustrate that the regioselectivity is substantially being controlled by the substituent(s) present on the acetylenic phenyl ring.

We report the first example of an efficient, Ag₂O nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides and isocoumarins via Sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively.     

The pathologic basis of Q-wave and non-Q-wave myocardial infarction: a cardiovascular magnetic resonance study

OBJECTIVES: The purpose of this study was to determine the pathologic basis of Q-wave (QW) and non-Q-wave (NQW) myocardial infarction (MI). BACKGROUND: The QW/NQW distinction remains in wide clinical use but the meaning of the difference remains controversial. We hypothesized that measurement of total MI size and transmural extent by late gadolinium enhancement cardiovascular magnetic resonance (CMR) would identify the pathologic basis of QWs. METHODS: A total of 100 consecutive patients with documented previous MI had electrocardiogram and CMR on the same day. Patients with acute MI within seven days were excluded. Left ventricular function and the size and transmural extent of MI were quantified in the three major arterial territories and correlated with the presence of QW. RESULTS: Subendocardial MI showed QW in 28%. Transmural MI showed NQW in 29%. Of all MIs, 48% were at some point transmural, and 99% of these were at some point non-transmural. As MI size and number of transmural segments increased, the probability of QW increased (anterior: total size chi-square = 53, p < 0.0001, transmural extent chi-square = 36, p < 0.0001; inferior: total size chi-square = 16, p = 0.001, transmural extent chi-square = 10, p = 0.001). These findings did not hold for lateral MI. In a multivariate model, the transmural extent of MI was not an independent predictor of QW when total size of MI was removed. The QW/NQW classification was a good test for size of MI (area under receiver operating characteristic curve: anterior 0.90, inferior 0.77). CONCLUSIONS: The QW/NQW distinction is useful, but it is determined by the total size rather than transmural extent of underlying MI.