Metformin and Dapagliflozin Attenuate Doxorubicin-Induced Acute Cardiotoxicity in Wistar Rats: An Electrocardiographic, Biochemical, and Histopathological Approach.

Doxorubicin is a widely used anticancer drug whose efficacy is limited due to its cardiotoxicity. There is no ideal cardioprotection available against doxorubicin-induced cardiotoxicity. This study aimed to investigate the anticipated cardioprotective potential of metformin and dapagliflozin against doxorubicin-induced acute cardiotoxicity in Wistar rats. At the beginning of the experiment, cardiac screening of experimental animals was done by recording an electrocardiogram (ECG) before allocating them into the groups. Thereafter, a total of thirty healthy adult Wistar rats (150-200 g) were randomly divided into five groups (n = 6) and treated for eight days as follows: group I (normal control), group II (doxorubicin control), group III (metformin 250 mg/kg/day), group IV (metformin 180 mg/kg/day), and group V (dapagliflozin 0.9 mg/kg/day). On the 7th day of the treatment phase, doxorubicin 20 mg/kg was administered intraperitoneal to groups II, III, IV, and V. On the 9th day (immediately after 48 h of doxorubicin administration), blood was collected from anesthetized animals for glucose, lipid profile, CK-MB & AST estimation, and ECG was recorded. Later, animals were sacrificed, and the heart was dissected for histopathological examination. We found that compared to normal control rats, CK-MB, AST, and glucose were significantly increased in doxorubicin control rats. There was a significant reversal of doxorubicin-induced hyperglycemia in the rats treated with metformin 250 mg/kg compared to doxorubicin control rats. Both metformin (180 mg/kg and 250 mg/kg) and dapagliflozin (0.9 mg/kg) significantly altered doxorubicin-induced ECG changes and reduced the levels of cardiac injury biomarkers CK-MB and AST compared to doxorubicin control rats. Metformin and dapagliflozin protected the cellular architecture of the myocardium from doxorubicin-induced myocardial injury. Current study revealed that both metformin and dapagliflozin at the FDA-recommended antidiabetic doses mitigated doxorubicin-induced acute cardiotoxicity in Wistar rats. The obtained data have opened the perspective to perform chronic studies and then to clinical studies to precisely consider metformin and dapagliflozin as potential chemoprotection in the combination of chemotherapy with doxorubicin to limit its cardiotoxicity, especially in patients with comorbid conditions like type II diabetes mellitus.

Ventricular strain patterns in multivalvular heart disease: a cross-sectional study.

Multivalvular heart disease (MVD) is an aggregate of regurgitant and/or stenotic lesions of at least two cardiac valves. Ventricular tissue deformation imaging is a powerful predictor of subclinical myocardial dysfunction in patients with MVD.The aim of this study was to examine the left and right ventricular strain patterns in MVD as well as observe any association between right-sided valvular involvement (tricuspid or pulmonary valve lesion) with that of aortic and/or mitral valve lesion. Patients with at least moderate forms of MVD were included in the present study. 72 patients with mean age of 56.69 ± 14.59 years and various presentations of MVD were finally enrolled in this study. The commonest cause for MVD was rheumatic heart disease in these patients. Conventional 2-dimensional parameters as well as tissue deformation imaging parameters were assessed in offline mode for these patients. The Mean ± SD values for various quantitative 2D echocardiographic conventional and tissue deformation imaging were assessed. It was observed that LV strain parameters including the global longitudinal strain (GLS) were preserved whereas the RV strain parameters were mildly reduced (RV GLS total is - 19.49 ± 6.08%). Also, when conventional echocardiographic parameters were assessed to see any association between aortic and/or mitral valve disease with that of right-sided valvular lesions (tricuspid or pulmonary); 2D conventional echocardiographic parameters like left atrial dimension (p = 0.034), TAPSE (tricuspid annular plane systolic excursion) (p < 0.001), RVSP (right ventricular systolic pressure) (p < 0.001) and IVC (inferior vena cava) dimensions (p < 0.001) showed a statistically significant result; whereas, when strain parameters for LV and RV were assessed, they did not show any statistical difference for the same. In this series of patients with significant MVD, our findings suggest that ventricular strain parameters may be reliable markers of myocardial dysfunction, but may alter depending on the underlying combination of MVD, and right ventricular strain should also be an important parameter while assessing different combinations of MVD.

Single Coronary Artery from Right Sinus of Valsalva: A Single Center Experience of Seven Cases.

Background: Single coronary artery (SCA) is a rare anomaly with a prevalence of 0.024-0.066%. Some anomalies are merely benign anatomical variants, whereas some can result in myocardial ischemia or life-threatening arrhythmia. Case Presentation. We described seven cases in which all three major coronaries emerged from the right sinus of Valsalva via a single ostium and supplied the vast majority of the myocardium. A smaller branch arising from the left sinus supplied a modest quantity of myocardium in some of those few cases. These SCA variations do not exactly fit into any existing classification. It is unclear whether we need to modify previous classification systems or newer classification systems. Conclusions: SCA is divided based on its anomalous course and is usually a benign condition but it may present with cardiovascular complications. Clinicians should be aware of this entity along with the role of CT angiogram in its diagnosis and management.

Effectiveness of ultrasonography-guided cardiac sympathetic denervation in acute control of electrical storm: A retrospective case series.

Background and Aims: Ultrasonography-guided left cardiac sympathetic denervation (LCSD) or bilateral cardiac sympathetic denervation (BCSD) may be a useful intervention in the electrical storm (ES) that persists despite pharmacological therapy. The aim of our study was to evaluate the effectiveness of ultrasonography-guided LCSD or BCSD in the acute control of ES. We conducted a retrospective case series of patients who underwent ultrasonography-guided CSD for control of ES at a tertiary care hospital. Material and Methods: Data of all patients who underwent unilateral or bilateral CSD were collected from January 2017 to December 2019. Eleven patients with ES refractory to standard antiarrhythmic therapy underwent ultrasonography-guided pharmacological CSD (eight underwent LCSD and three underwent BCSD). Quantitative data was expressed as mean and median with interquartile range (IQR). Non-quantitative data was expressed in proportions. Results: Eleven patients underwent ultrasonography-guided pharmacological CSD (eight underwent LCSD and three underwent BCSD). Six of the eleven patients were female (54.5%). Ischemia was the underlying substrate in nine patients (81.8%). Five patients (46%) had complete resolution of ventricular tachycardia (VT) after CSD and one had 90% reduction in episodes of VT. The median follow-up duration was 8 months inter-quartile range IQR (7-18). One patient succumbed to heart failure and one patient was lost to follow up. The other patients had no further events and were well at last follow up. Conclusion: Ultrasonography-guided pharmacological CSD is effective in the acute control of ES. It is easily performed with equipment that is readily available and relatively safe in terms of immediate complications and is an ideal second-line intervention when ES persists despite drug therapy.

A case series of rare neurological and cardio-pulmonary manifestations of thiamine deficiency in pregnancy and lactation.

Thiamine (vitamin B1) is a sulfur-containing, water-soluble vitamin that plays an essential role in energy metabolism and the tricarboxylic acid cycle. There is an increased need for vitamin B1 (1-1.2 mg daily) during pregnancy and lactation. Hyperemesis during pregnancy can cause severe polyneuropathy (Wernicke's encephalopathy) as a result of thiamine deficiency. Thiamine deficiency has also been associated with beriberi. A number of atypical cases with reversible right heart failure and severe pulmonary hypertension have also been reported in non-pregnant individuals, but have never been reported in pregnancy. Here we present five such cases of thiamine deficiency with neurological and cardio-pulmonary manifestations.

Role of deformation imaging in left ventricular non-compaction and hypertrophic cardiomyopathy: an Indian perspective.

BACKGROUND: Speckle tracking echocardiography (STE) has emerged as a novel feasible tool for the assessment of left ventricular rotational parameters. Since hypertrophic cardiomyopathy(HCM) shares morphologic features with left ventricular non-compaction (LVNC), we used this imaging modality to compare rotational mechanics between these two entities. RESULTS: We compared global and regional LV function and rotational mechanics between LVNC, HCM, and healthy subjects using STE. Longitudinal strain and torsion were obtained from echocardiographic images from parasternal short axis as well as standard LV apical views. Twelve patients with LVNC [mean age 46.12 ± 14.66 years; median 47.5 IQR (39.25-58.5) years] were compared with 18 HCM patients [mean age 49.48± 17.22 years; median 56 IQR (33-65) years] and 18 healthy subjects [mean age: 51.50± 12.51 years; median 51(45.75-58) years]. LVNC group showed a significantly reduced longitudinal strain at the apical region compared to HCM group (- 12.18 ± 6.25 vs - 18.37 ± 3.67; P < 0.05). Rigid body rotation(RBR) was found in 50% of patients whereas the other half had a normal rotation at the apex and the base. Among the patients with RBR, all patients had a uniform counterclockwise rotation. CONCLUSION: Longitudinal strain was impaired in both the forms of cardiomyopathy; however, LVNC showed a more significant reduction in the apical region compared to patients with HCM suggesting a development abnormality in these regions. A reduction in left ventricular torsion was specifically noted among patients with LVNC with a uniform anticlockwise rotation of LV base and apex.

Percutaneous intervention for restoration of patency of occluded lower limb arteriovenous dialysis access.

BACKGROUND: Arteriovenous (AV) fistula thrombosis is a serious complication in patients undergoing hemodialysis, often presenting with symptoms of venous hypertension, failure to dialysis and uremic symptoms. Treatment is aimed to provide symptomatic relief and to maintain hemodialysis access site patency. AIM: To describe our initial experience in the endovascular treatment of lower limb AV dialysis access (AV fistula) thrombosis and/or obstruction in patients undergoing hemodialysis. SETTINGS AND DESIGN: This was a retrospective study carried out in a tertiary care center. Study duration was 24 months. Follow-up was variable. MATERIALS AND METHODS: Two patients with chronic kidney disease with stage 5 renal failure undergoing hemodialysis presented with lower limb arteriovenous dialysis access (arteriovenous fistula) failure between July 2014 and September 2016. Both the patients underwent endovascular treatment and were analyzed retrospectively. RESULTS AND CONCLUSION: Both the patient underwent successful endovascular treatment for the failure of the lower limb AV dialysis access thrombosis and/or obstruction. One patient had minimal dye extravasation during manipulation of the guide wire, which ceased spontaneously. On follow-up, both patients maintained patency of the dialysis access and are undergoing successful hemodialysis. One patient had a recurrence of the thrombosis of the fistula at 9th month of the follow-up. Endovascular treatment was tried but we could not succeed. However, we found endovascular treatment safe and effective in treating AV fistula failures.

Chronic lithium intoxication: Varying electrocardiogram manifestations.

Lithium is a commonly used drug in psychiatric practice. It is used in the treatment of depression and bipolar disorder. It has a narrow therapeutic index with documented adverse effects even near therapeutic levels. It has myriad of manifestations at toxic levels. The cardiovascular effects range from relatively benign ST-T wave changes to fatal arrhythmias. We describe a case of lithium toxicity which presented as a junctional rhythm and later showed a variety of manifestations such as complete heart block, atrial fibrillation, sinus bradycardia, and finally reverted to sinus rhythm at par with serum lithium levels.

Patient profile and results of percutaneous transvenous mitral commissurotomy in mitral restenosis following prior percutaneous transvenous mitral commissurotomy vs surgical commissurotomy.

BACKGROUND: Patients with mitral restenosis who have undergone prior PTMC or surgical commissurotomy have increased. Predictors of outcome of repeat PTMC in either subgroup of patients may be different. AIMS AND OBJECTIVES: Aim was to assess and compare the immediate results of PTMC in patients who had undergone a prior PTMC or surgical commissurotomy. METHODS AND RESULTS: This is a single center, prospective, open label study. Of 70 patients in study, 44 (62.85%) patients had prior history of PTMC and 26 (37.15%) had prior surgical commissurotomy (closed/open). Average time from the initial procedure was 8.88 ± 5.36 years overall, 6.75 ± 3.38 for patients with prior PTMC and 16.73 ± 3.67 for patients with prior surgical commissurotomy. Prior PTMC group had 75% female, patients with prior surgical commissurotomy were older (44 ± 7 vs 33.57 ± 9.1 years, p = 0.001), had higher NYHA class (III/IV in100% vs 86.36%, p = 0.006.), higher atrial fibrillation (73.1% vs 25% p < 0.0001) and higher Wilkins' score (>8 in 88.46% vs 68.18%, p = 0.05). Successful PTMC was lower (65.4% vs 84.1%) in patients with prior surgical commissurotomy, though statistically not significant (p = 0.07). After PTMC, mitral valve area, PA systolic pressure, LA mean pressure and trans-mitral gradient were similar. Post procedure complications were not different in both the groups. CONCLUSION: PTMC for mitral restenosis in patients with prior surgical valvotomy is as effective as in patients with prior PTMC despite older age, higher NYHA class, higher Wilkins score and atrial fibrillation and can be considered in all patients with restenosis irrespective of the type of past procedures done.

Transcatheter right ventricular outflow tract stenting in children with postoperative infundibular stenosis and preserved pulmonary valve function.

Recurrent or residual right ventricular outflow tract obstruction after early surgical repair of congenital heart disease is one of the most frequent indications for either surgical or transcatheter reintervention. Transcatheter stent implantation across the stenotic right ventricular outflow tract or conduit is a safe and effective alternative to surgical reintervention. However, chronic deleterious effects of pulmonary regurgitation can potentially counterbalance the early improvement in clinical and hemodynamic parameters, sometimes necessitating further intervention. While there are several studies documenting safe and effective palliation by transcatheter right ventricular outflow tract stenting in infants with tetralogy of Fallot, literature on isolated infundibular stent implantation sparing the normal pulmonary valve in postoperative infundibular restenosis is very scant. We report our experience of safety and feasibility of transcatheter right ventricular outflow tract stent implantation while preserving the native pulmonary valve function in two children with infundibular stenosis after surgical repair of congenital heart disease.