Articles

I have recently described the origin of the second Ca2+ binding in the triggering of contractile activity in cardiac myofibrils that is the origin of the Ca2+ Hill coefficient of 2 for the ATPase. This site is not a simple protein binding site and cannot be measured by 45Ca2+ binding. The myofibril protein unit requirements are described by me and so are the consequences of disruption of the function of these units and the related medical outcomes. The purpose of this paper is to review the topic and extend the reasoning to the function of skeletal muscle and cite the literature that supports this.

Objective: Plaque morphology plays an important prognostic role in the occurrence of cerebrovascular events. Echolucent and heterogeneous plaques, in particular, carry an increased risk of subsequent stroke. Depending on the quality of the plaque echogenicity based on B-mode ultrasound examination, carotid plaques divide into a soft lipid-rich plaque and a hard plaque with calcification. The aim of this study was to investigate structural changes in the basement membrane of different carotid artery plaque types. Patients and methods: Biopsies were taken from 10 male patients (average age; 75 + 1 years) and 7 females (68 + 3 years). The study population included patients suffering from a filiform stenosis of the carotid artery, 8 patients with acute cerebrovascular events and 9 with asymptomatic stenosis. Scanning electron and polarised light microscopic investigations were carried out on explanted plaques to determine the morphology of calcified areas in vascular lesions. Results: By means of scanning electron microscopy, multiple foci of local calcification were identified. The endothelial layer was partially desquamated from the basement membrane and showed island-like formations. Polarised light microscopy allows us to distinguish between soft plaques with transparent structure and hard plaques with woven bone formation. Conclusion: The major finding of our study is the presence of woven bone tissue in hard plaques of carotid arteries, which may result from pathological strains or mechanical overloading of the collagen fibers. These data suggest a certain parallel with sclerosis of human aortic valves due to their similar morphological characteristics.

Introduction: One of the major complications among COVID-19 patients include cardiac arrhythmias. Commonest arrhythmia is sinus tachycardia which is usually associated with palpitation causing discomfort to patients. In this study, we present a comparative study of use of Ivabradine vs. Carvedilol for sinus tachycardia in post-COVID-19 infected patients. Method: 50 consecutive recovered COVID-19 patients with sinus tachycardia were included in this open labelled RCT. 25 patients received Ivabradine and remaining 25 received Carvedilol. Single therapy non-responders were treated with Ivabradine with Atorvastatin. Results: The mean age of all patients is 48.8±7.66 years (Males 49.5 ± 7.21 years; Females 47.68 ± 8.23 years). The mean heart rate (MHR) of all patients is 125.52 ± 9.07/min (Males 125.67 ± 8.78/min; Females 125.26 ± 9.5/min). After five days of single drug therapy the mean drop in the heart rate was 35.04 ± 10.55/min (Males 34.41 ± 9.71/min; Females 36.05 ± 11.72/min), resulting in 27.88 ± 8.11% (Males 27.38 ± 7.56%; Females 28.69 ± 8.89%) reduction in MHR. Among the two groups, the Carvedilol group showed improvement of MHR in 14(56%) patients; whereas in Ivabradine group 18(72%) patients improved out of 25 patients each (p: 0.2385). In the Carvedilol group the MHR reduced from 128.6 ± 8.44 to 95.68 ± 10.63 (p < 0.001), which is statistically significant; similarly, the Ivabradine group showed a MHR from 122.44 ± 8.62 to 85.28 ± 10.52 (p < 0.001). The monotherapy therapy non-responders were treated with dual-therapy of (Ivabradine + Atorvastatin). Discussion: Ivabradine is more effective in controlling heart rate compared to Carvedilol. Also, Ivabradine group scores very well in ‘patient-satisfaction’ with regards to symptom (palpitation) relief. Conclusion: The COVID-19 sequelae of sinus tachycardia can be better controlled with Ivabradine when compared to Carvedilol.

Ventricular assist device is a portable machine which is also called an artificial heart for the patients who have terminal heart failure. The device maintains the heart’s vital functions until the suitable donor is found for the heart transplantation. It can be applied to either ventricles or both (biventricular). Although the device provides independence for the patient, it also has life-threatening complications. Such as infection, stroke secondary to thromboembolism, hemorrhage depending on anticoagulant use, right heart failure… and most of the time it is really hard to manage those complications. We will present a case, who had ischemic stroke as a complication of VAD even though he has been using aspirin, warfarin and had effective INR value.

Post-extrasystolic potentiation (PESP) is a marker of contractile reserve and refers to the augmentation of left ventricular contractility due to preload recruitment and rise in intracellular calcium following a premature beat. In this case report we show that PESP might be a safe and helpful aid to evaluate low flow, low gradient aortic stenosis and contractile reserve in the cathlab, thereby reducing the potential risk of complications associated with intravenous dobutamine evaluation and reducing unnecessary testing.

With the discovery by Calghatgi (2013) that three common antibiotics (Abs) increased mitochondrial reactive oxygen (ROS) and lipid peroxide (LP) and depleted their natural absorbant glutathione led me to investigate further the potential impacts of these genotoxic substances on carcinogenesis. The range of impacts on mitochondria and cellular DNA varied by antibiotic to those consistent with known prior contributions to carcinogenesis. Specific cancers probably increased by these changes were HCC, RCC (KCC), CRC, cancer of the esophagus. Tumor suppressor gene mutations resulting from LP were noteworthy in this regard and mutations induced in CRC were consistent with those found in carcinogenesis of CRC. In addition depression of short chain fatty acids in microbiomes were found which depress the immune system increasing risk of all cancers. Many cancers were increased according to epidemiological studies linking Abs with elevated odds ratios, with one concern in particular, fatal breast cancer. The impact of loss of functionality of the mitochondria was also linked to depression of the citric acid cycle and therefore ATP which deflected metabolism to glycolysis, the Warburg mechanism also increasing risk of all cancers, favoured by cancer cells. In conclusion, some portion of many cancer types are probably increased in likelihood by number, type and frequency of Abs treatment and chronic residue exposure which varies from individual to individual. This led me to propose a three pronged carcinogenesis mechanism for Abs. 1. Cancer critical mutations 2. Immune depression 3. loss of mitochondrial functionality leading to Warburg effects. Damage to mitochondria were also noted by common pesticides tested in China and cancer associations were also found for many pesticides supporting a similar contributory etiology. Heart health concerns were raised by these findings because of the myriad mitochondria in the heart and because of long term reliability needs. Studies suggesting hearts were affected by Abs and pesticide exposure were presented. Because of their geographical ubiquitousness and the huge range of diseases associated with mitochondrial dysfunction, antibiotics and pesticides and bacteriocidal biocides are of concern for biodiversity and life in general. I propose research steps to evaluate Abs safety and suggest directions for further research and make suggestions on ways to ameliorate Abs toxicity.

Background: Tetralogy of Fallot (TOF) is a very common cyanotic congenital heart disease presenting early at birth with various degrees of cyanosis. If left uncorrected surgically, can lead to death. Objectives: This study is aimed at determining pattern and surgical outcome of children with teratology of Fallot in a budding health facility in India over a year period. Result: A total of 51 children were diagnosed of TOF over the period, of which 66.7% were males with mean age of 48.14 ± 45.36 months. The surgical outcome showed only 3.9% mortality. The death was among children >1 to 5 years. The mean number of days in intensive care unit (ICU) was 5.8 ± 11.2 days. 82.4% of the patients were off-pump post-operatively, compared to 17.6% with re-pump. Among those who had re-pump, 77.8% were males and among those without re-pump, 64.3% were likewise males (χ2 = 0.6, p = 0.41). About 92.2% (47/51) of patients had pulmonary regurgitation post-op, ranging from mild to moderate regurgitation. 51.1% of the regurgitations were mild while 25.5% and 23.4% were moderate and severe regurgitations respectively. Post-operative VSD was detected in 51% (26/51) of the patients. The post-op right ventricular pressure (RVOT) was significantly lower than that of pre-op pressure, 10.8 ± 1.5 mmHg vs. 31.7 ± 4.5 mmHg (pair t test = 8.7, p < 0.001). Conclusion: Timely surgical repair is crucial in alleviating several morbidity and mortality associated with teratology of fallot. Pulmonary regurgitation is a very common sequel after surgery and can result in death.

Background: Primary percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) is the most effective treatment modality in ST-segment elevation myocardial infarction (STEMI). Incidence of no flow is 8.8% - 10% in primary PCI of STEMI patients. Our aim was to study actual incidence and outcome of no flow patients. Methods: Five hundred and eighty primary PCI patients were enrolled and evaluated from 2016 January to 2017 December. We used drug eluting stents in all cases. Majority of our patients (> 90%) presented to emergency six hours after onset of symptoms. There were many patients where there was no flow even after mechanical thrombus aspiration and pharmacological vasodilator therapy. We have studied primary outcome (mortality) of no flow in those patients. Results: There were 44 cases of no flow in our series (7.75%). Involvement of Left anterior descending artery (LAD) was in eighteen patients. Right coronary artery (RCA) was culprit in twenty four cases. Only two cases were seen in LCX territory. One month mortality rate in no flow group was 50% and 6.25% in successful recanalization group. One year mortality was 12.5% in successful recanalization group and 66% in no flow group. Conclusion: Refractory no flow during STEMI intervention is associated with increased incidence of major adverse cardiovascular events (MACE). There is no established strategy to solve this phenomenon.

The normal adult heart is a well maintained machine that has a mechanism for growth replacement of the sarcomere that is lost by natural degeneration. This process ensures the heart has the strength of contraction to function correctly giving blood supply to the whole body. Some of the force of contraction of the sarcomere is transmitted to its major protein titin where its strength results in unfolding of a flexible section and release of a growth stimulant. The origin of all the cardiomyopathies can be traced to errors in this system resulting from mutations in a wide variety of the sarcomeric proteins. Too much or chronic tension transfer to titin giving increased growth resulting in hypertrophic cardiomyopathy (HCM) and too little leading to muscle wastage, dilated cardiomyopathy (DCM). HCM can ultimately lead to sudden cardiac death and DCM to heart failure. In this paper I show (1) a collection of the tension/ATPase calcium dependencies of cardiac myofibrils that define the mechanism of Ca2+ cooperativity. (2) I then reintroduce the stress/strain relationship to cardiomyopathies. (3) I then review the cardiomyopathy literature that contains similar Ca2+ dependency data to throw light on the mechanisms involved in generation of the types of myopathies from the mutations involved. In the review of cardiomyopathy there are two sections on mutations, the first dealing with those disrupting the Ca2+ cooperativity, i.e. the Hill coefficient of activation, leading to incomplete relaxation in diastole, chronic tension, and increased growth. Secondly dealing with those where the Ca2+ cooperativity is not affected giving either increased or decreased tension transfer to titin and changes in sarcomere growth. 

Background: Vascular closure devices (VCD) are routinely used to achieve haemostasis following percutaneous arterial procedures. The extravascular polyethylene-glycol based MynxGrip® device (Cardinal Health) received FDA approval for use in the closure of femoral veins, but so far limited data is available on its use, especially with concomitant use of anticoagulants. Method: This is a retrospective analysis of data from a single-centre on the effectiveness and complication rates following the use of the MynxGrip® device for femoral venous closure in patients undergoing diagnostic/interventional (temporary pacing during balloon aortic valvuloplasty, or electrophysiology) procedures utilising 5-7F sheaths. Results: 85 patients (mean age 74 years) underwent femoral venous closure with the MynxGrip® device. 51.8% were male. The rate of concomitant anticoagulant or antiplatelet use was 52.9%. Device deployment was 100% successful with full haemostasis in all cases. There were no major vascular complications (bleeding, thrombosis, or infections). There was one case of a minor small venous hematoma which did not require treatment. The mean length of stay was less than 1 day (67.1% patients discharged the same day) and overnight stay only indicated by interventional procedure. Conclusion: These data support safety and efficacy of the MynxGrip® device for femoral venous closure with same-day discharge, even with concomitant aggressive antiplatelet and anticoagulant use. It has the potential for use in other large bore venous access sites.