Gene therapy for heart failure: A novel treatment for the age old disease.

Across the globe, cardiovascular disease (CVD) is the leading cause of mortality. According to reports, around 6.2 million people in the United states have heart failure. Current standards of care for heart failure can delay but not prevent progression of disease. Gene therapy is one of the novel treatment modalities that promises to fill this limitation in the current standard of care for Heart Failure. In this paper we performed an extensive search of the literature on various advances made in gene therapy for heart failure till date. We review the delivery methods, targets, current applications, trials, limitations and feasibility of gene therapy for heart failure. Various methods have been employed till date for administering gene therapies including but not limited to arterial and venous infusion, direct myocardial injection and pericardial injection. Various strategies such as AC6 expression, S100A1 protein upregulation, VEGF-B and SDF-1 gene therapy have shown promise in recent preclinical trials. Furthermore, few studies even show that stimulation of cardiomyocyte proliferation such as through cyclin A2 overexpression is a realistic avenue. However, a considerable number of obstacles need to be overcome for gene therapy to be part of standard treatment of care such as definitive choice of gene, gene delivery systems and a suitable method for preclinical trials and clinical trials on patients. Considering the challenges and taking into account the recent advances in gene therapy research, there are encouraging signs to indicate gene therapy for heart failure to be a promising treatment modality for the future. However, the time and feasibility of this option remains in a situation of balance.

Ultrafiltration in Heart Failure: A Review.

Ultrafiltration is an effective method to get rid of fluid retention and congestion in patients with acute decompensated heart failure (HF) without affecting the circulating volume. Although its efficacy in comparison to diuretics is debatable, the evaluation of our analysis is based on various studies that comprise published clinical trials on ultrafiltration and studies comparing the efficacy of diuretics and ultrafiltration. Apart from this, we also look at literature that provides shortcomings of the said procedure and its scope for future advancements. Heart failure ultimately leads to volume overload, which is a highly concerning complication. Diuretics have been used as a first-line treatment for fluid overload but are becoming inefficacious due to the development of resistance and renal dysfunction. Ultrafiltration, on the other hand, is an attractive alternative to counter volume overload and congestion, which are unresponsive to medical therapy. There is also evidence that it significantly decreases the probability of future episodes of decompensation. There are, however, disagreements about whether ultrafiltration is an effective method to improve mortality in these patients. There is a lack of conclusive studies demonstrating the superiority of one fluid removal method over another. Hence, it is imperative to continue searching for the most effective method to treat congestion. Priority should be given to more mechanistic studies regarding ultrafiltration.

Ventricular Septal Rupture Management in Patients With Acute Myocardial Infarction: A Review.

Untreated myocardial infarction (MI) can potentially lead to many fatal complications which require immediate management. One of them is ventricular septal rupture (VSR) which necessitates the hemodynamic stabilization and closure of the septal rupture. Conventional treatment strategy involves surgical repair; however, percutaneous transcatheter repair using an occluder device is a promising upcoming approach. We conducted a detailed review of various published articles and examined the trends in incidence, risk factors, and pathophysiology of MI leading to VSR followed by an in-depth analysis of the various management strategies for the same. In the current clinical scenario, thrombolysis is an imperative management strategy that has been shown to decrease the occurrence of VSR by manifolds, more specifically in patients having ST-elevated MI. Delayed surgical closure remains the main treatment for post-infarction VSR. Other newer modalities, such as percutaneous closure devices and mechanical circulatory supports, are attractive alternative or complementary strategies to treat such patients, both postoperatively and perioperatively. However, earlier surgical repair in VSR increases the risk of mortality, and the optimal timing for VSR closure remains controversial. Despite surgical closure of VSR being the traditional treatment, it presents a considerably high operative risk. Although newer interventions such as percutaneous closure devices and mechanical circulatory supports provide impressive outcomes, their efficacy in high-risk patients remains inconclusive.

A Comparative Review of Vagal Nerve Stimulation Versus Baroreceptor Activation Therapy in Cardiac Diseases.

Sympathetic imbalance coupled with impairment of baroreceptor control is a key factor responsible for hemodynamic abnormalities in congestive heart failure. Vagal nerve stimulation (VNS) and baroreceptor activation therapy (BAT) are two novel interventions for the same. In this paper, we review the role of sympathovagal alterations in cardiac diseases like heart failure, arrhythmia, hypertension (HTN), etc. Studies like neural cardiac therapy for heart failure (NECTAR-HF), autonomic regulation therapy to enhance myocardial function and reduce progression of heart failure (ANTHEM-HF), and baroreflex activation therapy for heart failure (BEAT-HF), which comprise the history, efficacy, limitations, and current protocols, were extensively analyzed in contrast to one another. Vagal nerve stimulation reverses the reflex inhibition of cardiac vagal efferent activity, which is caused as a result of sympathetic overdrive during the course for heart failure. It has shown encouraging results in certain pre-clinical studies; however, there is also a possibility of serious cardiovascular adverse events if given in higher than the recommended dosage. Attenuated baroreflex sensitivity is attributed to cardiac arrhythmogenesis during heart failure. Baroreceptor activation therapy reverses this phenomenon. However, the surgical procedure for baroreceptor stimulation can have unwarranted complications, including worsening heart failure and hypertension. Considering the effectiveness of the given modalities and taking into account the inconclusive evidence of their adverse events, more clinical trials are needed for establishing the future prospects of these interventional approaches.

Prevalence of Traditional Risk Factors in First-Degree Relatives of Patients With Established Cardiovascular Disease.

INTRODUCTION: World Health Organization (WHO)/International Society of Hypertension (ISH) risk prediction charts are useful for predicting 10-year combined myocardial infarction and stroke risk (fatal and non-fatal). Hence the current study was conducted to assess the 10-year risk of cardiovascular disease among adults in Ahmedabad, India. AIMS: The primary aim of the study was to assess the cardiovascular risk among first-degree relatives of patients attending the outpatient clinic. Also, to create awareness regarding assessment of cardiovascular risk among the studied group. METHODS AND MATERIALS: A cross-sectional study was carried out among 372 first-degree relatives of patients at an out-patient cardiology clinic present in Vadaj, Ahmedabad. The WHO/ISH risk prediction chart for South-East Asia Region D (SEAR D) was used for calculating the 10-year cardiovascular risk. RESULTS: A maximum (80.10%) of the study participants were in the low-risk (<10%) category followed by 8.33% for moderate-risk (10-20%), 7.25% for moderately high-risk (20-30%), 2.42% for high-risk (30-40%) and 1.88% for very high-risk (>40%). CONCLUSION: WHO/ISH risk prediction charts provide a quick and effective way to assess and categorize the population in a low-resource setting which in turn helps in delivering focused intervention to the high-risk groups.

Humming (Simple Bhramari Pranayama) as a Stress Buster: A Holter-Based Study to Analyze Heart Rate Variability (HRV) Parameters During Bhramari, Physical Activity, Emotional Stress, and Sleep.

Objective In this study, our goal was to understand the comparative impact of humming, physical activity, emotional stress, and sleep on several heart rate variability (HRV) parameters, including the stress index (SI), and to assess the effectiveness of humming (simple Bhramari) as a stress buster based on the HRV parameters. Methods This pilot study assessed the long-term HRV parameters of 23 participants in terms of four activities: humming (simple Bhramari), physical activity, emotional stress, and sleep. The single-channel Holter device measured the readings, and data was analyzed using Kubios HRV Premium software for time and frequency-domain HRV parameters, including the stress index. Regarding statistical analysis, single-factor ANOVA followed by paired t-test was used to compare the results of HRV parameters "during" the four activities to understand if humming generates the outcome to enhance the autonomic nervous system. Results Our findings revealed that humming generates the lowest stress index compared to all three other activities (physical activity, emotional stress, and sleep). Several additional HRV parameters also supported the positive impact on the autonomic nervous, equivalent to stress reduction. Conclusions Humming (simple Bhramari) can be an effective stress-buster based on the assessment of several HRV parameters during its practice and in comparison with other activities. A regular daily humming routine can help enhance the parasympathetic nervous system and slow down sympathetic activation.

Evolving Coronary Stent Technologies - A Glimpse Into the Future.

One of the most widely accepted forms of treatment for coronary artery disease (CAD) is the implementation of stents into the vessel. This area of research is constantly evolving, ranging from bare-metal stents through drug-eluting stents and, more recently, approaching bioresorbable stents and polymer-free stents. This article reviews the evolution of all these devices and emphasizes how they might be further evolved to provide an optimal coronary stent and overcome unsolved challenges in stent development. We thoroughly evaluated a number of published studies in order to advance coronary stent technologies. Additionally, we looked for various literature that highlighted the inadequacies of the coronary stents that are currently available and how they might be modified to create the optimum coronary stent. Coronary stents have significantly improved clinical outcomes in interventional cardiology, but there are still a number of drawbacks, including an persisted risk of thrombosis due to endothelial injury and in-stent restenosis. Gene eluting stents (GES) and customized coronary stents with self-reporting stent sensors are appealing alternatives to existing stent approaches. Considering the adequacy of these gene eluting stents (GES), customized coronary stents produced by novel 4D printing technologies and integrated self-reporting stent sensors should be assumed for anticipating future advancements to optimal coronary stent devices; however, more interventional evidence is required to determine the future prospects of these stent innovations.

Impact of atmospheric variables on incidence of acute coronary syndrome amongst Gujarati Asian Indians - IOAPIC study.

OBJECTIVES: The study evaluated the effects of climatic conditions and its variables on incidence of ACS in Gujarati Asian Indians. METHODS: In this multicentric, retrospective, observational case control study of a total of 3256 patients, the Electronic Medical Records (EMS) of all 740 patients who were hospitalised for ACS at the 2 tertiary care centres of Ahmedabad over 3 years between January 2017 to December 2019 were compared with demographically matched 2516 non- ACS, CAD controls were compared for the impact of climatic parameters viz. temperature, barometric pressure, humidity as reported by monthly averages by the state meteorological department for monthly incidence of ACS. RESULTS: The highest number of ACS cases were observed during the month of September (N = 127; 27%) followed by August (N = 123; 26%). Higher humidity and decreasing atmospheric pressure were associated with highest occurrence of ACS in the state of Gujarat. ST elevation Myocardial Infarction (STEMI) was the most common type of ACS (N = 598; 80.8%). In ACS, the Coefficient of correlation for humidity was 0.712 (P = 0.009), while that for temperature was 0.506 (P = 0.093). Effect of atmospheric pressure was found to be significant with a negative Coefficient of correlation of -0.571 (P = 0.052). However amongst the controls, the coefficient of correlation for humidity was 0.062 (P = 0.722) and atmospheric pressure Correlation coefficient was 0.107 (P = 0.539) non-significant. CONCLUSIONS: The higher humidity/temperature and lower atmospheric pressure had a positive correlation with the incidence of ACS with highest incidence noted in August and September in the state of Gujarat.

Mechanical Assist Device-Assisted Percutaneous Coronary Intervention: The Use of Impella Versus Extracorporeal Membrane Oxygenation as an Emerging Frontier in Revascularization in Cardiogenic Shock.

The extracorporeal membrane oxygenation (ECMO) procedure aids in the provision of prolonged cardiopulmonary support, whereas the Impella device (Abiomed, Danvers, MA) is a ventricular assist device that maintains circulation by pumping blood into the aorta from the left ventricle. Blood is circulated in parallel with the heart by Impella. It draws blood straight into the aorta from the left ventricle, hence preserving the physiological flow. ECMO bypasses the left atrium and the left ventricle, and the end consequence is a non-physiological flow. In this article, we conducted a detailed analysis of various publications in the literature and examined various modalities pertaining to the use of ECMO and Impella for cardiogenic shocks, such as efficacy, clinical outcomes, cost-effectiveness, device-related complications, and limitations. The Impella completely unloads the left ventricle, thereby significantly reducing the effort of the heart. Comparatively, ECMO only stabilizes a patient with cardiogenic shock for a short stretch of time and does not lessen the efforts of the left ventricle ("unload" it). In the acute setting, both devices reduced left ventricular end-diastolic pressure and provided adequate hemodynamic support. By comparing patients on Impella to those receiving ECMO, it was found that patients on Impella were associated with better clinical results, quicker recovery, limited complications, and reduced healthcare costs; however, there is a lack of conclusive studies performed demonstrating the reduction in long-term mortality rates. Considering the effectiveness of given modalities and taking into account the various studies described in the literature, Impella has reported better clinical outcomes although more clinical trials are needed for establishing the effectiveness of these interventional approaches in revascularization in cardiogenic shock.

Immune Thrombocytopenia in Previously Healthy Individuals Following SARS-CoV-2 Vaccination (COVID-19 Immunization): A Descriptive Research of 70 Instances With a Focus on Biomarkers, Predictive Outcomes, and Consequences.

The coronavirus disease-2019 (COVID-19) pandemic is exacerbating the worldwide healthcare crisis. The pandemic has had an impact on nearly every system of our body. The Food and Drug Administration (FDA) gave immediate authorization of several vaccines to avoid critical COVID-19 outcomes following the rapid spread of the COVID-19. There have only been a few cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination-induced immune thrombocytopenia (ITP) so far. There should be enough information to identify whether some vaccination adverse effects, such as ITP, are caused by the vaccine. This study aims to determine how common ITP occurs after receiving the SARS-CoV-2 vaccine, as well as gender, age, symptoms, biomarkers, predicted outcomes, and sequelae. We looked at a number of research and compiled the best evidence of SARS-CoV-2 vaccine-induced thrombocytopenia currently available. To find the recommended reporting items, the search technique included keywords like "Immune thrombocytopenia," "COVID-19," "SARS-CoV-2," and "Vaccination." The search results were grouped using Boolean operators ("OR," "AND").

A Comprehensive Analysis of Myocarditis in Formerly Healthy Individuals Following SARS-CoV-2 Vaccination (COVID-19 Immunization).

Due to the rapid development of the coronavirus disease 2019 (COVID-19) pandemic, the Food and Drug Administration (FDA) expedited the authorization of immunizations to counteract life-threatening COVID-19 effects. COVID-19 immunization was seen as an essential component of surviving endemically with COVID-19. Although there were no major adverse event reports that mandated an early authorization of the mass vaccination approval in initial studies, a few significant adverse events were reported after real-world usage. The most prevalent adverse events are regional reactions, such as discomfort at the injection site. Anaphylactic shock and acute responses were quite infrequent. Current evidence strongly convince the community that the advantages of immunization outweigh the risks. The review investigates the potential adverse reaction in the form of myocarditis caused by the COVID-19 vaccine. Age, sexuality, vaccination type, clinical manifestations, and diagnostic modalities were among the confounding factors associated with vaccine-induced myocarditis. This picture depicts COVID-19 immunization-induced myocarditis and the treatment options available to practitioners. Further evaluation is needed to establish the underlying cause of this association. We compiled the most recent data on SARS-CoV-2 vaccine-induced myocarditis after reviewing available research. Information sources including PubMed and Google Scholar were evaluated retrospectively.

Repostioning of Telemedicine in Cardiovascular World Post-COVID-19 Pandemic.

Background: During the COVID-19 pandemic, telemedicine is a quickest expanding service solution to provide improved access to sophisticated healthcare that is efficient, cost-effective, and time-consuming. Methods: This analysis is evaluated on the basis of several studies that look at the history, benefits, various techniques, challenges, uses, and impact of telemedicine in the treatment of heart failure and cardiac rehabilitation as during COVID-19 outbreak. Results: Patients avoided or refused medical treatment during COVID-19 pandemic despite the risk of illness and the threat of infections spreading. Telemedicine has become a non-traditional form of care delivery due to better access and high-end technologies such as virtual consultations, face-to-face video, smartphone visits, two-way text communication, distant patient history, and distal characteristic assessment. Remote monitoring can help manage cardiovascular disease risk factors and increase patient participation in blood pressure, heart failure data, and workout or other activity progress. Conclusion: Based on the findings of past studies, we can infer that telemedicine is still an emerging subject in the treatment and management of cardiovascular disease. Telemedicine and similar technologies will also revolutionize healthcare services by expanding their reach and providing a big pool of database for better research and analysis.

Is Neutrophil-to-Lymphocyte Ratio a Predictor of Coronary Artery Disease in Western Indians?

INTRODUCTION: The current study was designed to evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with coronary artery disease (CAD) presence. We also aimed to propose a suitable cut-off of NLR for diagnosis of CAD in Western Indians. METHODS: Total 324 patients undergoing coronary angiography were enrolled and were subdivided into two groups: group 1 (n = 99; population without CAD) and group 2 (n = 225; population with CAD). RESULTS: The results indicated significant (p < 0.05) positive association between elevated levels of WBC, neutrophil, monocyte, NLR, hs-CRP, CPK-MB, and troponin I and disease presence. According to subgroup analysis, the association was more profound in male and older population. Among all the markers NLR showed the strongest predictive potential for CAD with highest odds ratio (1.495; 95% CI: 0.942-2.371; p < 0.048). Optimum cut-off of NLR for diagnosis of CAD was 2.13 (AUC-0.823; p < 0.001; sensitivity: 83.64%; specificity: 63.46%). Association of NLR with other biochemical markers such as hs-CRP, CPK-MB, and troponin I was also observed in quartile analysis. CONCLUSION: NLR is a simple indicator that could be effectively used for the diagnosis of CAD with a cut-off of 2.13 in Western Indian population.

Diagnostic accuracy of serum cystatin C for early recognition of contrast induced nephropathy in Western Indians undergoing cardiac catheterization.

AIMS: We aimed to compare the diagnostic efficacy of serum cystatin C (sCyC) for contrast induced nephropathy (CIN) in Western Indians undergoing cardiac catheterization. We also aimed to propose a clinically applicable cut-off of sCyC for early identification of CIN in this ethnic group. METHODS: In this prospective study, 253 patients undergoing coronary angiography and/or percutaneous coronary intervention were enrolled. The demographic and risk factor details, levels of sCr at baseline, 24 and 48h after the procedure, whereas baseline and 24h levels of sCyC were noted. Increase of 0.5mg/dl or ≥25% from baseline sCr was used to define CIN. Optimum cut off of sCyC for CIN diagnosis was obtained using Receiver Operating Characteristic (ROC) curve analysis. RESULTS: After 48h of contrast media (CM) exposure, the incidence of CIN was 12.25% (31 patients) according to sCr definition, where only 3.9% (10 patients) had sCr rise in 24h. Overall significant (p<0.0001) rise in mean levels of sCr (48h) and sCyC (24h) was observed in CIN patients. However, the mean sCr rise at 24h was non-significant. The optimum cut off of sCyC for diagnosing CIN was found to be a rise of ≥10% from baseline (AUC - 0.901; sensitivity - 100%, specificity - 77.89%). According to sCyC, 94 (37.15%) patients had CIN. CONCLUSION: We may conclude that a rise of ≥10% in sCyC at 24h could be used as a reliable marker for identification of CIN in western Indians undergoing cardiac catheterization.

Age and Sex Specific Reference Intervals for Modifiable Risk Factors of Cardiovascular Diseases for Gujarati Asian Indians.

Objective. We aimed to establish age and sex specific percentile reference data for cardiovascular risk factors such as lipids, sugar, blood pressure, and BMI in apparently healthy and disease-free Gujarati population. Methods. In this cross-sectional study, we enrolled 3265 apparently healthy and disease-free individuals of both genders residing in Gujarat state. Fasting samples of blood were used for biochemical estimations of lipids and sugar. The measurement of BMI and blood pressure was also done according to the standard guidelines. Age and gender specific 5th, 25th, 50th, 75th, 90th, and 95th percentiles were obtained. Results. The mean values of lipids, sugar, blood pressure, and BMI were significantly (p < 0.001) higher in males as compared to female population. Age-wise distribution trends showed increase in the risk factors from the 2nd decade until the 5th to 6th decade in most of the cases, where loss of premenopausal protection in females was also observed. Specific trends according to gender and age were observed in percentile values of various parameters. Conclusion. The outcome of current study will contribute significantly to proposing clinically important reference values of various lipids, sugar, blood pressure, and BMI that could be used to screen the asymptomatic Gujarati Indian population with a propensity of developing dyslipidemia, diabetes, blood pressure, and obesity.