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Impact of Malnutrition in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.
Scotti, A, Coisne, A, Granada, JF, Driggin, E, Madhavan, MV, Zhou, Z, Redfors, B, Kar, S, Lim, DS, Cohen, DJ, et al
Journal of the American College of Cardiology. 2023;(2):128-138
Abstract
BACKGROUND Although malnutrition is associated with poor prognosis in several diseases, its prognostic impact in patients with heart failure (HF) and secondary mitral regurgitation (SMR) is not understood. OBJECTIVES The purpose of this study was to assess the prevalence and impact of malnutrition in HF patients with severe SMR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone in the COAPT trial. METHODS Baseline malnutrition risk was calculated using the validated geriatric nutritional risk index (GNRI) score. Patients were categorized as having "malnutrition" (GNRI ≤98) vs "no malnutrition" (GNRI >98). Outcomes were assessed through 4 years. The primary endpoint of interest was all-cause mortality. RESULTS Among 552 patients, median baseline GNRI was 109 (IQR: 101-116); 94 (17.0%) had malnutrition. All-cause mortality at 4 years was greater in patients with vs those without malnutrition (68.3% vs 52.8%; P = 0.001). Using multivariable analysis, both baseline malnutrition (adjusted-HR [adj-HR]: 1.37; 95% CI: 1.03-1.82; P = 0.03) and randomization to TEER plus GDMT compared with GDMT alone (adj-HR: 0.65; 95% CI: 0.51-0.82; P = 0.0003) were independent predictors of 4-year mortality. In contrast, GNRI was unrelated to the 4-year rate of heart failure hospitalization (HFH), although TEER treatment reduced HFH (adj-HR: 0.46; 95% CI: 0.36-0.56). The reductions in death (adj-Pinteraction = 0.46) and HFH (adj-Pinteraction = 0.67) with TEER were consistent in patients with and without malnutrition. CONCLUSIONS Malnutrition was present in 1 of 6 patients with HF and severe SMR enrolled in COAPT and was independently associated with increased 4-year mortality (but not HFH). TEER reduced mortality and HFH in patients with and without malnutrition. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).
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Sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a systematic review and meta-analysis of randomized trials.
Ahmad, Y, Madhavan, MV, Stone, GW, Francis, DP, Makkar, R, Bhatt, DL, Howard, JP
European heart journal. Quality of care & clinical outcomes. 2022;(4):383-390
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Abstract
AIMS: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have now been evaluated for the treatment of heart failure in several placebo-controlled randomized controlled trials (RCTs) across various ejection fraction ranges, but these trials were powered for composite outcomes rather than individual clinical endpoints. We therefore performed a meta-analysis to assess their safety and efficacy on all-cause mortality, cardiovascular mortality, and heart failure hospitalizations. METHODS AND RESULTS We performed a prospectively registered random-effects meta-analysis of all RCTs comparing SGLT-2 inhibitors to placebo in patients with heart failure. The pre-specified primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, heart failure hospitalizations, and the composite of cardiovascular mortality or heart failure hospitalization. Four trials with 15 684 patients were eligible. The SGLT-2 inhibitor tested was empagliflozin in two trials, dapagliflozin in one trial, and sotagliflozin in one trial. The weighted-mean follow-up was 20.0 months. The hazard ratio (HR) for all-cause mortality was 0.91, 95% confidence interval (CI) 0.82-1.01, P = 0.071. There was a 12% reduction in cardiovascular mortality (HR 0.88, 95% CI 0.79 to 0.97, P = 0.012), and a 30% reduction in heart failure hospitalization (HR 0.70, 95% CI 0.64 to 0.77, P < 0.001). CONCLUSION SGLT-2 inhibitors significantly reduced cardiovascular mortality and heart failure hospitalizations in patients with heart failure. The effect appears consistent across three drugs studied in four trials. SGLT-2 inhibitors should become standard care for patients with heart failure.
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The role of vitamin D in cardiovascular disease and COVID-19.
Driggin, E, Madhavan, MV, Gupta, A
Reviews in endocrine & metabolic disorders. 2022;(2):293-297
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Abstract
Patients with pre-existing cardiovascular disease (CVD) are at high risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Further, COVID-19 infection is associated with numerous cardiovascular (CV) complications including arrhythmia, myocardial injury, cardiomyopathy, and thrombotic events. Increased susceptibility to COVID-19 and CV complications related to COVID-19 may be in part related to immune dysregulation and inflammation associated with CV disease which is exacerbated with viral infection. Vitamin D plays a major role in immune function and exerts anti-inflammatory effects, which may prove important in the context of CVD and COVID-19. To date, studies have shown minimal benefit for vitamin D supplementation in patients with COVID-19, though there are no studies specific to patients with CVD and related complications. Further, given that vitamin D has important protective effects on the CV system, including augmentation of myocardial contractility and anti-thrombotic effects, it is unknown if supplementation with vitamin D can mitigate CVD complications associated with COVID-19.
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Lipid-Modulating Agents for Prevention or Treatment of COVID-19 in Randomized Trials.
Talasaz, AH, Sadeghipour, P, Aghakouchakzadeh, M, Dreyfus, I, Kakavand, H, Ariannejad, H, Gupta, A, Madhavan, MV, Van Tassell, BW, Jimenez, D, et al
medRxiv : the preprint server for health sciences. 2021
Abstract
Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multi-organ manifestations. Lipid modulating agents may be useful in treating patients with COVID-19. They may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglycerides portends worse outcome in patients with COVID-19. Upon a systematic search, 40 RCTs with lipid modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrates RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for management or prevention of COVID-19. This manuscript summarizes the ongoing or completed randomized controlled trials (RCTs) of lipid modulating agents in COVID-19 and the implications of these trials for patient management.
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Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review.
Talasaz, AH, Sadeghipour, P, Aghakouchakzadeh, M, Dreyfus, I, Kakavand, H, Ariannejad, H, Gupta, A, Madhavan, MV, Van Tassell, BW, Jimenez, D, et al
Journal of the American College of Cardiology. 2021;(16):1635-1654
Abstract
Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.
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Post-acute COVID-19 syndrome.
Nalbandian, A, Sehgal, K, Gupta, A, Madhavan, MV, McGroder, C, Stevens, JS, Cook, JR, Nordvig, AS, Shalev, D, Sehrawat, TS, et al
Nature medicine. 2021;(4):601-615
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
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Extrapulmonary manifestations of COVID-19.
Gupta, A, Madhavan, MV, Sehgal, K, Nair, N, Mahajan, S, Sehrawat, TS, Bikdeli, B, Ahluwalia, N, Ausiello, JC, Wan, EY, et al
Nature medicine. 2020;(7):1017-1032
Abstract
Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
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Efficacy and safety of intravascular lithotripsy for the treatment of peripheral arterial disease: An individual patient-level pooled data analysis.
Madhavan, MV, Shahim, B, Mena-Hurtado, C, Garcia, L, Crowley, A, Parikh, SA
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2020;(5):959-968
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BACKGROUND Peripheral arterial disease (PAD) is one of the most common manifestations of atherosclerotic disease worldwide. Peripheral arterial calcification reduces acute success and long-term patency of endovascular therapy for PAD. Several calcium modification devices are available for use in peripheral interventions. Outcomes after peripheral intravascular lithotripsy (IVL), a novel approach using pulsatile sonic waves to treat luminal and medial calcium in patients with PAD, have not been extensively characterized. Therefore, we sought to perform an individual patient-level data (IPD) pooled analysis of available studies to evaluate the efficacy and safety of IVL in the treatment of PAD. METHODS AND RESULTS We pooled IPD, including baseline and procedural variables, from five prospective studies which assessed IVL in the treatment of patients with extensive peripheral artery calcification. Final postprocedural percent diameter stenosis (%DS) and procedural angiographic complications were assessed by independent core laboratory. Efficacy endpoints were analyzed using linear mixed effects models and safety endpoints were tabulated overall and by vascular bed. Among 336 patients who underwent endovascular revascularization with use of IVL, there was a significant reduction between pre-procedural and final %DS of 55.1% (95% confidence interval 53.3-57.0%, p < .0001). Core-laboratory assessed lesion-level complications, including flow-limiting dissections (Types D-F), vessel perforation, distal embolization, thrombus, abrupt closure, and no reflow, occurred in 4/328 (1.22%) of treated lesions. CONCLUSIONS The present IPD of five prospective studies, marking the largest analysis to date evaluating the use of IVL in significantly calcified PAD lesions, demonstrates this treatment strategy to be both effective and safe.
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MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19.
Bilezikian, JP, Bikle, D, Hewison, M, Lazaretti-Castro, M, Formenti, AM, Gupta, A, Madhavan, MV, Nair, N, Babalyan, V, Hutchings, N, et al
European journal of endocrinology. 2020;(5):R133-R147
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The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.
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Relation between coronary calcium and major bleeding after percutaneous coronary intervention in acute coronary syndromes (from the Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trials).
Généreux, P, Madhavan, MV, Mintz, GS, Maehara, A, Kirtane, AJ, Palmerini, T, Tarigopula, M, McAndrew, T, Lansky, AJ, Mehran, R, et al
The American journal of cardiology. 2014;(6):930-5
Abstract
Percutaneous coronary intervention (PCI) of calcified coronary lesions has been associated with increased rates of adverse ischemic events. However, the potential association between the presence and severity of calcific deposits and bleeding complications has yet to be investigated. Data from 6,855 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) or ST-segment elevation myocardial infarction (STEMI) treated with PCI were pooled from 2 large-scale randomized controlled trials-Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction. Patients were stratified into 3 groups according the grade of target PCI lesion calcium (none to mild, moderate, and severe) as assessed by an independent angiographic core laboratory. Thirty-day bleeding event rates were assessed and compared among groups. In the total cohort undergoing PCI, none-to-mild target lesion calcium was found in 4,665 patients (68.1%), moderate target lesion calcium in 1,788 patients (26.1%), and severe target lesion calcium in 402 patients (5.9%). The 30-day rates of non-coronary artery bypass graft surgery major bleeding increased significantly with each degree of coronary calcium (none to mild = 5.9%, moderate = 7.2%, and severe = 11.2%, p = 0.0003). By multivariable analysis, presence of severe calcium was an independent predictor of non-coronary artery bypass graft major bleeding after PCI (hazard ratio 1.54, 95% confidence interval 1.09 to 2.17, p = 0.01). In conclusion, in patients undergoing PCI for non-ST-segment elevation acute coronary syndrome and ST-segment elevation myocardial infarction, target lesion coronary calcium was an independent predictor of major bleeding events. Further studies are needed to elucidate mechanisms underlying this finding and to optimize treatment of this high-risk population.