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Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Peter A. McCullough, Paul E. Alexander, Robin Armstrong, Cristian Arvinte, Alan F. Bain, Richard P. Bartlett, Robert L. Berkowitz, Andrew C. Berry, Thomas J. Borody, Joseph H. Brewer, Adam M. Brufsky, Teryn Clarke, Roland Derwand, Alieta Eck, John Eck, Richard A. Eisner, George C. Fareed, Angelina Farella, Silvia N. S. Fonseca, Charles E. Geyer Jr., Russell S. Gonnering, Karladine E. Graves, Kenneth B. V. Gross, Sabine Hazan, Kristin S. Held, H. Thomas Hight, Stella Immanuel, Michael M. Jacobs, Joseph A. Ladapo, Lionel H. Lee, John Littell, Ivette Lozano, Harpal S. Mangat, Ben Marble, John E. McKinnon, Lee D. Merritt, Jane M. Orient, Ramin Oskoui, Donald C. Pompan, Brian C. Procter, Chad Prodromos, Juliana Cepelowicz Rajter, Jean-Jacques Rajter, C. Venkata S. Ram, Salete S. Rios , Harvey A. Risch, Michael J. A. Robb, Molly Rutherford, Martin Scholz, Marilyn M. Singleton, James A. Tumlin, Brian M. Tyson, Richard G. Urso, Kelly Victory, Elizabeth Lee Vliet, Craig M. Wax, Alexandre G. Wolkoff, Vicki Wooll, Vladimir Zelenko
Reviews in Cardiovascular Medicine    2020, 21 (4): 517-530.   DOI: 10.31083/j.rcm.2020.04.264
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The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.
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Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients
Matthieu MILLION, Jean-Christophe LAGIER, Hervé TISSOT-DUPONT, Isabelle RAVAUX, Catherine DHIVER, Christelle TOMEI, Nadim CASSIR, Léa DELORME, Sébastien CORTAREDONA, Sophie AMRANE, Camille AUBRY, Karim BENDAMARDJI, Cyril BERENGER, Barbara DOUDIER, Sophie EDOUARD, Marie HOCQUART, Morgane MAILHE, Coralie PORCHETO, Piseth SENG, Catherine TRIQUET, Stéphanie GENTILE, Elisabeth JOUVE, Audrey GIRAUD-GATINEAU, Herve CHAUDET, Laurence CAMOIN-JAU, Philippe COLSON, Philippe GAUTRET, Pierre-Edouard FOURNIER, Baptiste MAILLE, Jean-Claude DEHARO, Paul HABERT, Jean-Yves GAUBERT, Alexis JACQUIER, Stéphane HONORE, Katell GUILLON-LORVELLEC, Yolande OBADIA, Philippe PAROLA, Philippe BROUQUI, Didier RAOULT
Reviews in Cardiovascular Medicine    2021, 22 (3): 1063-1072.   DOI: 10.31083/j.rcm2203116
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We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32–57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06–0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients—Odds ratio 0.31 [0.20–0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.
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Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection
Brian C. Procter, Casey Ross, Vanessa Pickard, Erica Smith, Cortney Hanson, Peter A. McCullough
Reviews in Cardiovascular Medicine    2020, 21 (4): 611-614.   DOI: 10.31083/j.rcm.2020.04.260
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There is an emergency need for early ambulatory treatment of Coronavirus Disease 2019 (COVID-19) in acutely ill patients in an attempt to reduce disease progression and the risks of hospitalization and death. Such management should be applied in high-risk patients age > 50 years or with one or more medical problems including cardiovascular disease. We evaluated a total of 922 outpatients from March to September 2020. All patients underwent contemporary real-time polymerase chain reaction (PCR) assay tests from anterior nasal swab samples. Patients age 50.5 ± 13.7 years (range 12 to 89), 61.6% women, at moderate or high risk for COVID-19 received empiric management via telemedicine. At least two agents with antiviral activity against SARS-CoV-2 (zinc, hydroxychloroquine, ivermectin) and one antibiotic (azithromycin, doxycycline, ceftriaxone) were used along with inhaled budesonide and/or intramuscular dexamethasone consistent with the emergent science on early COVID-19 treatment. For patients with high severity of symptoms, urgent in-clinic administration of albuterol nebulizer, inhaled budesonide, and intravenous volume expansion with supplemental parenteral thiamine 500 mg, magnesium sulfate 4 grams, folic acid 1 gram, vitamin B12 1 mg. A total of 320/922 (34.7%) were treated resulting in 6/320 (1.9%) and 1/320 (0.3%) patients that were hospitalized and died, respectively. We conclude that early ambulatory (not hospitalized, treated at home), multidrug therapy is safe, feasible, and associated with low rates of hospitalization and death. Early treatment should be considered for high-risk patients as an emergency measure while we await randomized trials and guidelines for ambulatory management.
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Positive and negative impact of social media in the COVID-19 era
A. Verner Venegas-Vera, Gates B Colbert, Edgar V. Lerma
Reviews in Cardiovascular Medicine    2020, 21 (4): 561-564.   DOI: 10.31083/j.rcm.2020.04.195
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Social Media usage has been shown to increase in situations of natural disaster and other crises. It is crucial for the scientific community to understand how social media works in order to enhance our capabilities and make a more resilient community. Through social media communication, the scientific community can collaborate around the globe in a faster way the most important findings of a disease, with a decreased knowledge transition time to other healthcare providers (HCPs). This is greatly important to coordinate research and knowledge during a time of uncertainty and protentional fake news. During the 2020 global pandemic, social media has become an ally but also a potential threat. High volumes of information compressed into a short period can result in overwhelmed HCPs trying to discern fact from noise. A major limitation of social media currently is the ability to quickly disseminate false information which can confuse and distract. Society relies on educated scientists and physicians to be leaders in delivering fact-based information to the public. For this reason, in times of crises it is important to be leaders in the conversation of social media to guide correct and helpful information and knowledge to the masses looking for answers.
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Role of hydroxychloroquine in multidrug treatment of COVID-19
Peter A. McCullough, Raphael B. Stricker, Harvey A. Risch
Reviews in Cardiovascular Medicine    2021, 22 (3): 545-546.   DOI: 10.31083/j.rcm2203063
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Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review
Aaron Y. Kluger, Kristen M. Tecson, Clay M. Barbin, Andy Y. Lee, Edgar V. Lerma, Zachary P. Rosol, Janani Rangaswami, Norman E. Lepor, Michael E. Cobble, Peter A. McCullough
Reviews in Cardiovascular Medicine    2018, 19 (2): 41-49.   DOI: 10.31083/j.rcm.2018.02.907
Abstract5220)      PDF(pc) (1438KB)(8892)       Save
In this systematic review, we sought to summarize the 3 recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials (Dapagliflozin Effect on CardiovasculAR Events (DECLARE-TIMI 58), Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, and Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)) and to explore the potential causes for their different results. We found that the major adverse cardiovascular event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14% for DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME, respectively. DECLARETIMI 58 had the fewest cardiorenal events (across treatment and control arms) and EMPA-REG OUTCOME the most. DECLARE-TIMI 58 used alternative inclusion criterion for baseline renal function (creatinine clearance ≧ 60 mL/min) compared to the other trials (estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 bodysurface area). Therefore, the DECLARE-TIMI 58 study cohort had higher eGFR (mean eGFR 85.2 mL/min/1.73 m2 compared to 76.5 and 74 in CANVAS and EMPAREG OUTCOME, respectively); this may have caused the difference in results. Additionally contributing to the high event rate in EMPA-REG OUTCOME was the requirement of prior confirmed cardiovascular disease (CVD), resulting in 99.2% of patients with CVD compared to only 65.6% and 40.6% in CANVAS and DECLARE-TIMI 58, respectively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.
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The Cardiovascular effects of chocolate
Jose P. Garcia, Adrian Santana, Diego Lugo Baruqui, Nicholas Suraci
Reviews in Cardiovascular Medicine    2018, 19 (4): 123-127.   DOI: 10.31083/j.rcm.2018.04.3187
Abstract4628)      PDF(pc) (424KB)(4297)       Save
The antioxidants as polyphenols, especially flavanols present in cocoa, exert a favorable effect on endothelium vasodilation, modulate inflammatory markers, and decrease platelet aggregation, lipid oxidation and insulin resistance. Recent nutritional intervention trials and molecular studies demonstrate that consumption of cocoa, particularly rich in flavanols, is beneficial to promote cardiovascular health. This review describes the cardiovascular effects of chocolate.
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Treatment models of cardiac rehabilitation in patients with coronary heart disease and related factors affecting patient compliance
Yun Tian, Pingji Deng, Bing Li, Jieqiong Wang, Ju Li, Yulan Huang, Yan Zheng
Reviews in Cardiovascular Medicine    2019, 20 (1): 27-33.   DOI: 10.31083/j.rcm.2019.01.53
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Coronary heart disease is a serious threat to human health. In China, medical care for the population has been focused on therapy with little follow-up of treated patients. The efficacy of therapy; however, is highly dependent on post-therapy recovery. Cardiac rehabilitation can significantly enhance patient physical strength and help delay and prevent the development of coronary atherosclerosis. Although the clinical significance of cardiac rehabilitation has been established, the compliance of patients is generally low. In efforts to improve patient compliance, domestic and foreign researchers have extensively studied and applied treatment models of cardiac rehabilitation according to the specific conditions and cultural background of each country. This study aimed to review the treatment models of cardiac rehabilitation in patients with coronary heart disease and related factors affecting patient compliance to provide a better perspective of how patients with coronary heart disease can benefit from cardiac rehabilitation.

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Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection
Peter A. McCullough, John Eidt, Janani Rangaswami, Edgar Lerma, James Tumlin, Kevin Wheelan, Nevin Katz, Norman E. Lepor, Kris Vijay, Sandeep Soman, Bhupinder Singh, Sean P. McCullough, Haley B. McCullough, Alberto Palazzuoli, Gaetano M. Ruocco, Claudio Ronco
Reviews in Cardiovascular Medicine    2020, 21 (1): 1-7.   DOI: 10.31083/j.rcm.2020.01.42
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Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.

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Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy
Jun Zhang, Kristen M. Tecson, Peter A. McCullough
Reviews in Cardiovascular Medicine    2020, 21 (3): 315-319.   DOI: 10.31083/j.rcm.2020.03.126
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Great attention has been paid to endothelial dysfunction (ED) in coronavirus disease 2019 (COVID-19). There is growing evidence to suggest that the angiotensin converting enzyme 2 receptor (ACE2 receptor) is expressed on endothelial cells (ECs) in the lung, heart, kidney, and intestine, particularly in systemic vessels (small and large arteries, veins, venules, and capillaries). Upon viral infection of ECs by severe acute respiratory syndrome coronarvirus 2 (SARS-CoV-2), ECs become activated and dysfunctional. As a result of endothelial activation and ED, the levels of pro-inflammatory cytokines (interleukin -1, interleukin-6 (IL-6), and tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1), von Willebrand factor (vWF) antigen, vWF activity, and factor VIII are elevated. Higher levels of acute phase reactants (IL-6, C-reactive protein, and D-dimer) are also associated with SARS-CoV-2 infection. Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. Here we present an update on ED-relevant vasculopathy in COVID-19. Further research for ED in COVID-19 patients is warranted to understand therapeutic opportunities.

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Coronary Chronic Total Occlusion (CTO): A Review
Christian O. Koelbl, Zoran S. Nedeljkovic, Alice K. Jacobs
Reviews in Cardiovascular Medicine    2018, 19 (1): 33-39.   DOI: 10.31083/j.rcm.2018.01.906
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Coronary artery chronic total occlusions (CTO) are frequently encountered during coronary angiography; however percutaneous recanalization has historically been technically challenging and an important determinant for referral to coronary artery bypass surgery or for medical therapy alone. Recent advances in interventional equipment and innovative approaches to crossing CTO have significantly increased the success rate of percutaneous treatment. Although there is only one relevant randomized control trial (RCT) performed to date, several large, nonrandomized studies have consistently reported improvement in clinical outcomes, including improved survival and relief of angina, when successful percutaneous treatment of CTO was compared with unsuccessful revascularization. These positive observational results have encouraged the initiation of several RCTs which will provide more robust evidence on clinical outcomes of CTO-PCI compared with guideline-directed medical therapy (GDMT) alone.
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SARS-CoV-2 infection and the COVID-19 pandemic: a call to action for therapy and interventions to resolve the crisis of hospitalization, death, and handle the aftermath
Peter A. McCullough, Kris Vijay
Reviews in Cardiovascular Medicine    2021, 22 (1): 9-10.   DOI: 10.31083/j.rcm.2021.01.301
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No abstract present.
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Pathophysiology of Congestive Heart Failure
Gary S. Francis, W.H. Wilson Tang
Reviews in Cardiovascular Medicine    2003, 4 (S2): 14-20.  
Abstract1949)      PDF(pc) (133KB)(2898)       Save
Heart failure is a clinical syndrome characterized by impaired structure and/or function of the heart, leading to dyspnea and fatigue at rest or with exertion. The pathophysiology of heart failure is complex, and there is no single lesion. Any form of heart disease can lead to heart failure. Most heart failure can be explained by well-recognized etiologic factors, though ostensibly healthy patients may harbor risk factors for the later development of heart failure. A fundamental response to myocardial injury or altered loading conditions includes “remodeling” of the heart, so that the size, shape, and function of the affected chamber is grossly distorted. This is accompanied by a constellation of biologic changes, best recognized in advanced cases of heart failure. These multiple alterations may be primary or secondary events but, nonetheless, add importantly to the morbidity and mortality of the patients. More emphasis should be placed on recognition and correction of risk factors related to the development of heart failure.
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Evaluation of acute chest pain: Evolving paradigm of coronary risk scores and imaging
Edris Alderwish, Emily Schultz, Zain Kassam, Michael Poon, Neil Coplan
Reviews in Cardiovascular Medicine    2019, 20 (4): 231-244.   DOI: 10.31083/j.rcm.2019.04.589
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There is a broad differential diagnosis for patients presenting with acute chest pain. History, physical examination, electrocardiogram, and serial troponin assays are pivotal in assessing patients with suspected acute coronary syndrome. However, if the initial workup is equivocal, physicians are faced with a challenge to find the optimal strategy for further triage. Risk stratification scores have been validated for patients with known acute coronary syndrome, such as the TIMI and GRACE scores, but there may be limitations in undifferentiated chest pain patients. Advancements in imaging modalities such as coronary computed tomography angiography and the addition CT derived fractional flow reserve, have demonstrated utility in evaluating patients presenting with acute chest pain. With this article, we aim to provide a comprehensive review of the non-invasive modalities that are available to evaluate acute chest pain patients suspected of cardiac etiology in the emergency room. We also added a focus on new imaging modalities that have shown to have prognostic implications in stable ischemic heart disease.

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Cardiac sarcoidosis: diagnosis and management
Eleftherios Markatis, Andreas Afthinos, Emmanouil Antonakis, Ilias C Papanikolaou
Reviews in Cardiovascular Medicine    2020, 21 (3): 321-338.   DOI: 10.31083/j.rcm.2020.03.102
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Sarcoidosis is a chronic inflammatory disease of unknown etiology characterized by multi-organ involvement. End-organ disease consists of granulomatous inflammation, which if left untreated or not resolved spontaneously, leads to permanent fibrosis and end-organ dysfunction. Cardiac involvement and fibrosis in sarcoidosis occur in 5-10% of cases and is becoming increasingly diagnosed. This is due to increased clinical awareness among clinicians and new diagnostic modalities, since magnetic resonance imaging and positron-emission tomography are emerging as “gold standard” tools replacing endomyocardial biopsy. Despite this progress, isolated cardiac sarcoidosis is difficult to differentiate from other causes of arrhythmogenic cardiomyopathy. Cardiac fibrosis leads to congestive heart failure, arrhythmias and sudden cardiac death. Immunosuppressives (mostly corticosteroids) are used for the treatment of cardiac sarcoidosis. Implantable devices like a cardioverter-defibrillator may be warranted in order to prevent sudden cardiac death. In this article current trends in the pathophysiology, diagnosis and management of cardiac sarcoidosis will be reviewed focusing on published research and latest guidelines. Lastly, a management algorithm is proposed.

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Utility of telemedicine in the COVID-19 era
Gates B. Colbert, A. Verner Venegas-Vera, Edgar V. Lerma
Reviews in Cardiovascular Medicine    2020, 21 (4): 583-587.   DOI: 10.31083/j.rcm.2020.04.188
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Previously it has been demonstrated that telehealth (TH) could help cover the gaps in health attention in remote locations. Today the expanded capabilities have transformed TH delivery, and from the beginning of the coronavirus pandemic, it has remained one of our biggest allies. Telehealth has become a central piece in patient healthcare delivery during COVID-19 pandemic era. Telehealth allows health care services to reach patients in their homes, keeping other patients safe through social distancing and maintaining self-quarantine. Within this administration of health, TH allows health care providers to focus more resources to pandemic usage and at the same time continue caring for the health of non COVID-19 patients. During this time, clinicians are expanding knowledge about TH capabilities, such as application of forward triage as a tool to avoid patient contact in emergency departments. While previously TH was mainly used for primary care needs, specialized and urgent care health is now being utilized more than ever before. These advantages comes with limitations, some of them include a limited physical exam, lack of access to diagnostic testing or imaging, and many other pitfalls and persistent unmet needs. The 2020 pandemic has led to significant improvements leading into the next generation of telemedicine.
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Anti-hypertensive efficacy of amlodipine dosing during morning versus evening: A meta-analysis
Yifan Luo, Lixiang Ren, Mingyan Jiang, Yang Chu
Reviews in Cardiovascular Medicine    2019, 20 (2): 91-98.   DOI: 10.31083/j.rcm.2019.02.31814
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A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.550.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.

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Application of injectable hydrogels for cardiac stem cell therapy and tissue engineering
Keshav Narayan Alagarsamy, Weiang Yan, Abhay Srivastava, Vincenzo Desiderio, Sanjiv Dhingra
Reviews in Cardiovascular Medicine    2019, 20 (4): 221-230.   DOI: 10.31083/j.rcm.2019.04.534
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Cardiovascular diseases are responsible for approximately one-third of deaths around the world. Among cardiovascular diseases, the largest single cause of death is ischemic heart disease. Ischemic heart disease typically manifests as progressive constriction of the coronary arteries, which obstructs blood flow to the heart and can ultimately lead to myocardial infarction. This adversely affects the structure and function of the heart. Conventional treatments lack the ability to treat the myocardium lost during an acute myocardial infarction. Stem cell therapy offers an excellent solution for myocardial regeneration. Stem cell sources such as adult stem cells, embryonic and induced pluripotent stem cells have been the focal point of research in cardiac tissue engineering. However, cell survival and engraftment post-transplantation are major limitations that must be addressed prior to widespread use of this technology. Recently, biomaterials have been introduced as 3D vehicles to facilitate stem cell transplantation into infarct sites. This has shown significant promise with improved cell survival after transplantation. In this review, we discuss the various injectable hydrogels that have been tried in cardiac tissue engineering. Exploring and optimizing these cell-material interactions will guide cardiac tissue engineering towards developing stem cell based functional 3D constructs for cardiac regeneration.

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Epidemiology and pathogenesis of heart failure with preserved ejection fraction
Nandini Nair
Reviews in Cardiovascular Medicine    2020, 21 (4): 531-540.   DOI: 10.31083/j.rcm.2020.04.154
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Heart failure (HF) is a complex syndrome that affects approximately 6.5 million adults in the United States. About half of the 6.5 million adults with HF are estimated to be individuals with heart failure with preserved ejection fraction (HFpEF). It is a common cause for poor quality of life, increased health-care resource utilization, and early mortality. HF incidence has risen to epidemic proportions in the recent years. This review attempts to address the epidemiology and pathophysiology of HFpEF. The incidence of HFpEF increased from 48% to 57% from 2000 to 2007 with a slight decrease in 2010 to 52%. The temporal trends in heart failure show an overall stable incidence of HF over the last two decades with increasing incidence of HFpEF and decreasing HFrEF incidence. Many etiologies contribute to the development of HFpEF which makes the treatment very challenging. Pathophysiology of HFpEF is multifaceted stemming from several disease-specific aspects of inflammation and endothelial function, cardiomyocyte hypertrophy and fibrosis, ventricular-vascular uncoupling, pulmonary hypertension and chronotropic incompetence. Hence identifying the risk factors and etiologies is imperative to achieve optimal outcomes in this population. Newer insights into myocardial remodeling have led to an interesting finding of abnormal fibroblasts in HFpEF which are apoptosis resistant and initiate the development of an abnormal myocardial matrix resulting in initiation and progression of the disease. Upregulation of ROS has also been implicated in HFpEF. Further investigation could provide new avenues to target therapeutics specifically to stop initiation and progression of fibrosis.
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Epidemiology of cardiovascular risk in chronic kidney disease patients: the real silent killer
Michele Provenzano, Giuseppe Coppolino, Teresa Faga, Carlo Garofalo, Raffaele Serra, Michele Andreucci
Reviews in Cardiovascular Medicine    2019, 20 (4): 209-220.   DOI: 10.31083/j.rcm.2019.04.548
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Chronic kidney disease is a growing public health problem, as its prevalence and incidence have almost doubled over the last three decades. Chronic kidney disease is defined as the presence of an estimated glomerular filtration rate < 60 ml/min/1.73 m2 and/or proteinuria ≥ 0.150 g/24 h. It has been demonstrated that both proteinuria and reduction in estimated glomerular filtration rate can predict the development of fatal and non-fatal cardiovascular events, regardless of traditional cardiovascular risk factors, namely blood pressure, smoking habit, cholesterol, age, gender. This relationship is found in the general population, high-risk cohorts and in patients referred to Nephrologists (tertiary care). The accuracy by which proteinuria or estimated glomerular filtration rate can predict these events, exceeds that obtained by the combination of all the other traditional risk factors. These important findings have led to chronic kidney disease being considered as a cardiovascular risk equivalent. Although this needs further investigation, a great effort has been made to reduce the cardiovascular risk in chronic kidney disease patients. Indeed, many clinical trials have been carried-out testing the effect of antihypertensive, proteinuria-lowering, lipid-lowering and hypoglycemic agents on cardiovascular risk protection. All these trials reduced, but did not eliminate, the overall cardiovascular risk. Future studies should be undertaken to identify high cardiovascular risk patients and novel therapeutic targets for cardiovascular protection in chronic kidney disease patients.

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Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19
Jun Zhang, Peter A. McCullough, Kristen M. Tecson
Reviews in Cardiovascular Medicine    2020, 21 (3): 339-344.   DOI: 10.31083/j.rcm.2020.03.131
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There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.

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Alcohol, Heart Disease, and Mortality: A Review
Robert A.Vogel
Reviews in Cardiovascular Medicine    2002, 3 (1): 7-13.  
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Observational data suggest that moderate alcohol consumption is associated with reduced all-cause mortality compared with that associated with either abstinence or heavy drinking. Alcohol consumption reduces cardiovascular disease risk primarily by increasing production of high-density lipoprotein cholesterol, and possibly by increasing plasminogen, tissue plasminogen activator, and endothelial function, and decreasing platelet aggregability, fibrinogen, and lipoprotein(a). Red wine, containing antioxidants, has been purported to be especially cardioprotective. However, red wine consumption is not associated with reduced all-cause mortality in European countries, and American studies have found no relationship between the type of alcohol consumed and cardiovascular risk. Alcohol appears to be more cardioprotective if consumed with meals (possibly owing to protection against postprandial endothelial protection) and in moderation daily (as opposed to binge drinking). Despite the wealth of observational data, it is not absolutely clear that alcohol reduces cardiovascular risk, because no randomized controlled trials have been performed. Alcohol should never be recommended to patients to reduce cardiovascular risk as a substitute for the well-proven alternatives of appropriate diet, exercise, and drugs. Alcohol remains the number three cause of preventable premature death in this country, and the risk of alcohol habituation, abuse, and adverse effects must be considered in any patient counseling.
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Cardiovascular system and COVID-19: manifestations and therapeutics
Ajay K. Mahenthiran, Ashorne K. Mahenthiran, Jo Mahenthiran
Reviews in Cardiovascular Medicine    2020, 21 (3): 399-409.   DOI: 10.31083/j.rcm.2020.03.124
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The world is currently in the midst of a daunting global pandemic due to SARS-CoV-2 viral infection and associated COVID-19 disease. Healthcare professionals are tasked with the challenge of managing diverse multisystem clinical manifestations of this infection. Although acute hypoxic respiratory failure is the hallmark of severe COVID-19 disease, there have been diverse manifestations within the cardiovascular (CV) system that each pose unique therapeutic challenges. Of these manifestations, myocardial injury and right ventricular dysfunction are the most common, however, heart failure, circulatory shock, cardiomyopathy, arrhythmia, and vascular thrombosis have been noted as well. Furthermore, these CV related manifestations portend greater morbidity and mortality, which requires clinicians to be familiar with the most recent information to provide informed patient care. Although there are limited treatment options available for COVID-19, it is imperative that the potential cardiovascular implications of these therapies are considered in these patients. This review highlights the pathophysiological mechanisms of and therapeutics for CV manifestations of COVID-19 as well as the CV implications of proposed COVID-19 therapies. Since our hospital-based providers are the frontline caregivers battling this pandemic, the aim of this review is to assist with clinical decision-making for optimal patient outcomes while maintaining a safe environment for healthcare personnel.

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Usefulness of ultrasound in the management of aortic dissection
Fengju Liu, Lianjun Huang
Reviews in Cardiovascular Medicine    2018, 19 (3): 103-109.   DOI: 10.31083/j.rcm.2018.03.3182
Accepted: 29 April 2019

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Aortic dissection is an acute large vessel disease characterized by sudden onset, rapid disease progression and high mortality. Color doppler ultrasound analyzed the morphological and hemodynamic status of aortic branches before and after aortic dissection surgery, including carotid, subclavian, renal, celiac, superior mesenteric and iliac arteries. Transthoracic echocardiography, vascular ultrasound, transesophageal echocardiography, intravascular ultrasound and contrast-enhanced ultrasonography are complementary to aortic multi-slice spiral computed tomography angiography for diagnosis, treatment and prognostic evaluation.
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LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials
Xiaogen Chen, Chunna Jin, Lan Xie, Meixiang Xiang
Reviews in Cardiovascular Medicine    2020, 21 (1): 113-118.   DOI: 10.31083/j.rcm.2020.01.2
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Patients with heart failure (HF) are prone to combine with renal insufficiency. Recently, LCZ696 has been used in the treatment of HF, but whether LCZ696 is better than angiotensin converting enzyme inhibitors/angiotensin receptor antagonists (ACEI/ARB) in renal protection for HF patients has not been investigated. Therefore, we conducted a meta-analysis focusing on LCZ696 and its role in preservation of renal function in HF patients. Embase, PubMed, the Cochrane Library and ClinicalTrials.gov databases were electronically searched for available randomized controlled trials (RCTs). HF patients taking LCZ696 or ACEI/ARB were assessed for renal adverse events. The last search date was Sep 20, 2019. A total of 14959 patients from 6 trials were included in this meta-analysis. As compared to ACEI/ARB, LCZ696 significantly reduced the risk of renal function deterioration (odds ratio 0.77, 95% confidence interval 0.61-0.97, P = 0.02). In summary, LCZ696 may have superior renal protection in HF patients compared with ACEI/ARB.

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Continuation of Chronic Heart Failure Therapies During Heart Failure Hospitalization - a Review
Girish Singhania, Abutaleb A. Ejaz, Peter A. McCullough, Aaron Y. Kluger, Saravanan Balamuthusamy, Bhagwan Dass, Namrata Singhania, Adhish Agarwal
Reviews in Cardiovascular Medicine    2019, 20 (3): 111-120.   DOI: 10.31083/j.rcm.2019.03.562
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Randomized controlled trials have demonstrated the benefits of guideline-directed medical therapy in the outpatient setting for treatment of chronic heart failure. However, the benefits of continuation (or discontinuation) of major chronic heart failure therapies when treating acute heart failure during hospitalization are less clear. Real and anticipated worsening renal function, hyperkalemia and hypotension are the three major reasons for discontinuation of renin-angiotensin-aldosterone system inhibitors during hospitalization, and a failure to resume renin-angiotensin-aldosterone system inhibitors before discharge could worsen cardiovascular outcomes. Available data, mostly observational, shows that continuation or initiation of renin-angiotensin-aldosterone system inhibitors appears efficacious, safe, and well tolerated in majority of acute heart failure patients during hospitalization. Worsening renal function portends poor prognosis only if associated with congestion in acute heart failure, and clinicians should not de-escalate diuretic therapy routinely for worsening renal function.

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Management of heart failure in patients with end-stage kidney disease on maintenance dialysis: a practical guide
Megan S. Joseph, Maryse Palardy, Nicole M. Bhave
Reviews in Cardiovascular Medicine    2020, 21 (1): 31-39.   DOI: 10.31083/j.rcm.2020.01.24
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End-stage kidney disease (ESKD) and heart failure (HF) often coexist and must be managed simultaneously. Multidisciplinary collaboration between nephrology and cardiology is critical when treating patients with such complicated physiology. There is no "one-size-fits-all" approach to the evaluation of patients with new left ventricular systolic dysfunction, and diagnostic testing should be adapted to an individual's risk factors. Guideline-directed medical therapy (GDMT) for systolic heart failure should be employed in these patients. While limited randomized data exist, observational data and post hoc analyses suggest that GDMT, including renin angiotensin aldosterone system inhibitors, is associated with improved cardiovascular outcomes and can be safely initiated at low doses with close monitoring of kidney function in this population. Volume status is typically managed through ultrafiltration, so close communication between cardiology and nephrology is necessary to achieve a patient's optimal dry weight and mitigate intradialytic hypotension. Patient education and engagement regarding sodium and fluid restriction is crucial, and symptom burden should be reassessed following changes to the dialysis regimen.

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The Role of Oxidative Stress in the Metabolic Syndrome
Adam Whaley-Connell, Peter A. McCullough, James R. Sowers
Reviews in Cardiovascular Medicine    2011, 12 (1): 21-29.   DOI: 10.3909/ricm0555
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Loss of reduction-oxidation (redox) homeostasis and generation of excess free oxygen radicals play an important role in the pathogenesis of diabetes, hypertension, and consequent cardiovascular disease. Reactive oxygen species are integral in routine in physiologic mechanisms. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways that promote impairments in insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. Redox control of metabolic function is a dynamic process with reversible pro- and anti-free radical processes. Labile iron is necessary for the catalysis of superoxide anion, hydrogen peroxide, and the generation of the damaging hydroxyl radical. Acute hypoxia and cellular damage in cardiovascular tissue liberate larger amounts of cytosolic and extracellular iron that is poorly liganded; thus, large increases in the generation of oxygen free radicals are possible, causing tissue damage. The understanding of iron and the imbalance of redox homeostasis within the vasculature is integral in hypertension and progression of metabolic dysregulation that contributes to insulin resistance, endothelial dysfunction, and cardiovascular and kidney disease.
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Cardiogenic Shock: A Lethal Complication of Acute Myocardial Infarction
David R. Holmes
Reviews in Cardiovascular Medicine    2003, 4 (3): 131-135.  
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Cardiogenic shock is a serious complication of myocardial infarction (MI) that affects approximately 7% of MI patients, accounting for the majority of all deaths related to acute infarction. Shock is typically the result of a massive amount of damage to the left ventricular myocardium; its defining characteristics are hypotension (systolic blood pressure [SBP] of 90 mm Hg or less, or in chronically hypertensive patients a drop in SBP of 30 mm Hg or more) and hypoperfusion. Shock occurs more frequently in ST-segment elevation MI (STEMI) patients than in non-STEMI patients. Revascularization, either with angioplasty or coronary bypass graft surgery, is associated with better outcomes than intensive medical therapy in patients with shock. Adjunctive therapies include vasopressor therapy, mechanical ventilatory support, and intra-aortic balloon pump counterpulsation (IABP). IABP can stabilize some patients and may make revascularization safer. Other adjunctive therapies being investigated include improved mechanical support devices, induction of systemic hypothermia, use of supersaturated oxygen, and, as medical therapy, administration of L-NMMA.
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Inhibition of the Sodium–Proton Antiporter (Exchanger) is a Plausible Mechanism of Potential Benefit and Harm for Drugs Designed to Block Sodium Glucose Co-transporter 2
Peter A. McCullough, Aaron Y. Kluger, Kristen M. Tecson, Clay M. Barbin, Andy Y. Lee, Edgar V. Lerma, Zachary P. Rosol, Sivan L. Kluger, Janani Rangaswami
Reviews in Cardiovascular Medicine    2018, 19 (2): 51-63.   DOI: 10.31083/j.rcm.2018.02.021
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Clinical trials of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and comorbid cardiovascular and kidney disease have shown reductions in major adverse cardiovascular events, heart failure hospitalizations, and attenuation of the progression of kidney disease. The magnitude of benefit appears to be greater than expected due to glycemic control, reduced blood pressure, and loss of adiposity. This impact is also independent from reduced renal function and lesser degrees of natriuresis and glycosuria. However, these agents have also been associated with limb amputation, Fournier’s gangrene, diabetic ketoacidosis, metabolic bone disease, and increased hematopoiesis. A strong off-target effect of SGLT2i on the sodium–proton antiporter (exchanger) on the cell surface and intracellular organelles explains the wide-ranging effects of these agents. By slowing the restoration of pH within cells, SGLT2i activate secondary processes that mimic ischemic preconditioning in the heart and kidney and increased hematopoiesis in bone marrow which would explain salutary effects. Conversely, the inability to rapidly recover pH in ischemic peripheral tissues explains the progression of diabetic extremity ulcers, gangrene, propensity for metabolic bone disease, and diabetic ketoacidosis in patients who are predisposed. This paper will review the evidence for the strong off-target effect of SGLT2i on the sodium-proton exchanger and its potential effect on the organ systems and processes in which SGLT2i appear to have activity.
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SARS-CoV-2 infection in patients with diabetes mellitus and hypertension: a systematic review
Niloofar Deravi, Mobina Fathi, Kimia Vakili, Shirin Yaghoobpoor, Marzieh Pirzadeh, Melika Mokhtari, Tara Fazel, Elahe Ahsan, Samad Ghaffari
Reviews in Cardiovascular Medicine    2020, 21 (3): 385-397.   DOI: 10.31083/j.rcm.2020.03.78
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After the emergence of the novel 2019 coronavirus disease in P. R. China, this highly contagious disease has been currently spread out to almost all countries, worldwide. Novel 2019 coronavirus disease, Middle East respiratory syndrome, and severe acute respiratory syndrome are reported to cause a higher risk for severe infections in patients with chronic comorbidities, such as hypertension and diabetes. These severe infections can contribute to higher rates of morbidity and mortality in these patients. In the present review, we discussed the role and underlying mechanisms of the two most common chronic diseases, type-2 diabetes mellitus and hypertension, in clinical manifestations and disease severity of novel 2019 coronavirus disease, Middle East respiratory syndrome and severe acute respiratory syndrome, with the hope to provide evidence for better decision-making in the treatment of this vulnerable population.

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Modulation of the autonomic nervous system through mind and body practices as a treatment for atrial fibrillation
M. Usmaan Bashir, Anjali Bhagra, Suraj Kapa, Christopher J. McLeod
Reviews in Cardiovascular Medicine    2019, 20 (3): 129-137.   DOI: 10.31083/j.rcm.2019.03.517
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Atrial fibrillation is the most common symptomatic arrhythmia that is associated with stroke. Contemporary management of the disease is focused on anticoagulation to prevent stroke, coupled with catheter ablation to limit symptoms and prevent deleterious cardiac remodeling. Emerging data highlights the importance of lifestyle modification by managing sleep apnea, increasing physical activity, and weight loss. There is significant data that supports a link between the autonomic nervous system, arrhythmia development, and atrial fibrillation therapy. It is likely that lifestyle modification through these techniques that are aimed to reduce stress may also mediate atrial fibrillation development through this mechanism. This review examines how mind and body practices such as meditation, yoga, and acupuncture may influence the autonomic nervous system and mitigate atrial fibrillation progression and regression. Available evidence from molecular and anatomical levels through to clinical observations and translational clinical trials were scrutinized and a case established for these interventions as potential powerful mediators of anti-arrhythmic benefit.

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Contrast induced acute kidney injury in interventional cardiology: an update and key guidance for clinicians
Federico Ronco, Giuseppe Tarantini, Peter A. McCullough
Reviews in Cardiovascular Medicine    2020, 21 (1): 9-23.   DOI: 10.31083/j.rcm.2020.01.44
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Contrast-induced acute kidney injury (CI-AKI) is a serious complication that can affect outcome and prognosis of patients undergoing percutaneous diagnostic and interventional procedures in catheterization laboratories. There have been advancements in case definition and epidemiology. Additionally strategies have emerged that are positioned to have impact in the catheterization laboratory for patients undergoing cardiovascular procedures. The aim of this review is to provide the state-of-the-art of diagnosis, prevention and management of CI-AKI in interventional cardiology.

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Pandemic lockdown, healthcare policies and human rights: integrating opposed views on COVID-19 public health mitigation measures
Alexandru Burlacu, Radu Crisan-Dabija, Adrian Covic, Catalin Raiu, Ionut Mavrichi, Iolanda Valentina Popa, Manuel Lillo-Crespo
Reviews in Cardiovascular Medicine    2020, 21 (4): 509-516.   DOI: 10.31083/j.rcm.2020.04.274
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The issue of the COVID-19 pandemic occupies the agenda of the whole world. The pivot of this pandemic is a crucial element that has become almost as important as the virus itself, namely the lockdown. Although, the rationale for lockdown is well-sustained by strong epidemiological arguments, exploring the 'other' unwanted consequences of the contemporary COVID-19 pandemic is mandatory for coagulating a robust agreed position against the numerous problems generated by the SARS-CoV-2 virus. Starting from the rationale of the lockdown, in this paper we explored and exposed the other consequences of the COVID19 pandemic measures such as the use or abuse of human rights and freedom restrictions, economic issues, marginalized groups and eclipse of all other diseases. Our scientific attempt is to coagulate a stable position and integrate current opposing views by advancing the idea that rather than applying the uniform lockdown policy, one could recommend instead an improved model targeting more strict and more prolonged lockdowns to vulnerable risk/age groups while enabling less stringent measures for the lower-risk groups, minimizing both economic losses and deaths. Rigorous (and also governed by freedom) debating may be able to synchronize the opposed perspectives between those advocating an extreme lockdown (e.g., most of the epidemiologists and health experts), and those criticizing all restrictive measures (e.g., economists and human rights experts). Confronting the multiple facets of the public health mitigation measures is the only way to avoid contributing to history with yet another failure, as seen in other past epidemics.
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Advances in epigenetic regulation of vascular aging
Jing Jin, Yufeng Liu, Lihong Huang, Hong Tan
Reviews in Cardiovascular Medicine    2019, 20 (1): 19-25.   DOI: 10.31083/j.rcm.2019.01.3189
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Vascular aging is a major risk factor and driver of agerelated cardiovascular diseases (CVD). Atherosclerosis, hypertension, and other CVD lead to vascular dysfunction that involves multiple pathological processes such as oxidative stress, endothelial dysfunction, inflammation, and autophagy. Epigenetics refers to genetic changes that occur when the DNA remains unchanged that include DNA methylation, histone modification, and non-coding RNA. It has been reported that epigenetics plays an effective regulatory role in CVD and affects cardiovascular repair function. Presently, drugs targeting epigenetics have applications in malignant tumors and inflammation. Therefore, exploration of epigenetic mechanisms in vascular aging will allow us to understand the pathogenesis of diseases related to vascular aging. This review focuses on the pathological changes in vascular aging and analyzes the relationship between vascular aging and epigenetics. Additionally, this review focuses on the pathogenesis of vascular aging related diseases from a new perspective in order to develop epigenetic-based treatment strategies for patients with age-related cardiovascular diseases.

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Cardiac rehabilitation using telemedicine: the need for tele cardiac rehabilitation
Ritu Thamman, Rajesh Janardhanan
Reviews in Cardiovascular Medicine    2020, 21 (4): 497-500.   DOI: 10.31083/j.rcm.2020.04.201
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Cardiac Rehabilitation programs have shown to improve outcomes. The COVID-19 pandemic has posed barriers to these programs. A virtual platform might be a good solution to these challenges. Tele Cardiac Rehabilitation and remote patient monitoring provide an excellent alternative practical solution.
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Critical complications of COVID-19: A descriptive meta-analysis study
Kimia Vakili, Mobina Fathi, Aiyoub Pezeshgi, Ashraf Mohamadkhani, Mohammadreza Hajiesmaeili, Mostafa Rezaei-Tavirani, Fatemeh Sayehmiri
Reviews in Cardiovascular Medicine    2020, 21 (3): 433-442.   DOI: 10.31083/j.rcm.2020.03.129
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The coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has rapidly spread worldwide, causing a pandemic. The main objective of this meta-analysis was to evaluate the prevalence of the most common symptoms and complications of COVID-19. All relevant studies on the clinical complications of COVID-19 have been identified by searching two web databases (i.e., PubMed and Scopus). Afterward, the relevant data were extracted from the selected studies, and then analyzed by the STATA (Version 14) random-effects model. The 30 studies selected for our meta-analysis covered 6,389 infected patients. The prevalence rates of the most common symptoms were as follows: fever: 84.30% (95% CI: 77.13-90.37; I2 = 97.74%), cough: 63.01% (95% CI: 57.63-68.23; I2 = 93.73%), dyspnea: 37.16% (95% CI: 27.31-47.57%; I2 = 98.32%), fatigue: 34.22% (95% CI: 26.29-42.62; I2 = 97.29%), and diarrhea: 11.47% (95% CI: 6.96-16.87; I2 = 95.58%). Moreover, the most prevalent complications were found to be acute respiratory distress syndrome (ARDS) with 33.15% (95% CI: 23.35-43.73; I2 = 98.56%), arrhythmia with 16.64% (95% CI: 9.34-25.5; I2 = 92.29%), acute cardiac injury with 15.68% (95% CI: 11.1-20.97; I2 = 92.45%), heart failure with 11.50% (95% CI: 3.45-22.83; I2 = 89.48%), and acute kidney injury (AKI) with 9.87% (95% CI: 6.18-14.25; I2 = 95.64%). In this study, we assessed the prevalence of the main clinical complications of COVID-19, and found that following respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.

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Hyperkalemia in heart failure: current treatment and new therapeutic perspectives
Chiara Minà, Laura Ajello, Gabriele Di Gesaro, Calogero Falletta, Francesco Clemenza
Reviews in Cardiovascular Medicine    2020, 21 (2): 241-252.   DOI: 10.31083/j.rcm.2020.02.8
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Hyperkalemia in heart failure is a condition that can occur with relative frequency because it is related to pathophysiological aspects of the disease, and favored by drugs that form the basis of chronic cardiac failure therapy. Often, associated comorbidities, such as kidney failure or diabetes mellitus can further adversely affect potassium levels. Hyperkalemia can result in acute and even severe clinical manifestations that put patients at risk. On the other hand, the finding of hyperkalemia in a chronic context can lead to a reduction in dosages or to suspension of drugs such as angiotensin-converting enzymes inhibitor, angiotensin receptor blocker, angiotensin receptor neprilysin inhibitor, and mineralcorticoid receptor antagonist, first line in the treatment of the disease, with negative effects in prognostic terms. Therapies for the correction of hyperkalemia have so far mainly concerned the treatment of acute clinical pictures. Newly developed molecules, such as patiromer or sodium zirconium cyclosilicate, now open new prospectives in the long-term management of hyperkalemia, and allow us to glimpse the possibility of a better titration of the cardinal drugs for heart failure, with consequent positive effects on patient prognosis. The aim of this review is to focus on the problem of hyperkalemia in the setting of heart failure, with particular regard to its incidence, its prognostic role, and the underlining pathophysiological mechanisms. The review also provides an overview of therapeutic strategies for correcting hyperkalemia in acute and chronic conditions, with a focus on the new potassium binders that promise to improve management of heart failure.
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Infective endocarditis after TAVI: a meta-analysis and systematic review of epidemiology, risk factors and clinical consequences
Grigore Tinica, Andrei Tarus, Mihai Enache, Bogdan Artene, Iulian Rotaru, Alberto Bacusca, Alexandru Burlacu
Reviews in Cardiovascular Medicine    2020, 21 (2): 263-274.   DOI: 10.31083/j.rcm.2020.02.68
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Infective endocarditis (IE) represents one of the most challenging clinical entities, requiring a multidisciplinary approach. The increasing number of surgical and transcatheter heart valves replacements performed annually lead to a higher incidence of prosthetic valve endocarditis. Transcatheter aortic valve implantation (TAVI) brought a new alternative for the treatment of aortic stenosis and a new subgroup of IE with its features. We aimed to compare the incidence of IE in TAVI and surgical valve replacement (SAVR) to identify risk factors for TAVI-IE, evaluate the possible impact on mortality, and clarify the best treatment strategies. A digital scan in PubMed and SCOPUS databases was performed. 68 publications were selected to perform a meta-analysis and systematic review on epidemiology, risk factors, and mortality predictors in TAVI-IE. No significant difference in IE rate was noted between patients with TAVI and those with SAVR for in-hospital, early, mid-term and late IE. Male gender, intubation, new pacemaker implantation IE and CKD were correlated with TAVI-IE. Surgical treatment was performed in 22.3% of cases. Overall mortality for the pooled cohort was 38.3%. In a multivariate logistic regression model, surgical treatment and self-expandable device were linked to lower mortality in TAVI-IE. Even if the invasive procedure can trigger bacteremia, exposing the TAVI valve to future infection, no significant difference in IE rate was noted in our analysis between patients with TAVI and those with SAVR for in-hospital, early, mid-term and late IE. Surgical treatment of TAVI-IE can be a viable option in patients with a prohibitive risk score.
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Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence
Jasjit S. Suri, Anudeep Puvvula, Misha Majhail, Mainak Biswas, Ankush D. Jamthikar, Luca Saba, Gavino Faa, Inder M. Singh, Ronald Oberleitner, Monika Turk, Saurabh Srivastava, Paramjit S. Chadha, Harman S. Suri, Amer M. Johri, Vijay Nambi, J Miguel Sanches , Narendra N. Khanna, Klaudija Viskovic, Sophie Mavrogeni, John R. Laird, Arindam Bit, Gyan Pareek, Martin Miner, Antonella Balestrieri, Petros P. Sfikakis, George Tsoulfas, Athanasios Protogerou, Durga Prasanna Misra, Vikas Agarwal, George D. Kitas, Raghu Kolluri, Jagjit Teji, Michele Porcu, Mustafa Al-Maini, Ann Agbakoba, Meyypan Sockalingam, Ajit Sexena, Andrew Nicolaides, Aditya Sharma, Vijay Rathore, Vijay Viswanathan, Subbaram Naidu, Deepak L. Bhatt
Reviews in Cardiovascular Medicine    2020, 21 (4): 541-560.   DOI: 10.31083/j.rcm.2020.04.236
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Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AIbased platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.
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  • Volume 22, Issue 3