Emergence of the natural history of Myhre syndrome: 47 patients evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016-2023).

Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.

Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

BACKGROUND: Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra. AIM: Aim Our study aims to compare TAVR outcomes in patients with BAV versus tricuspid aortic valves (TAV). METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane trials. Studies were included if they included BAV and TAV patients undergoing TAVR with quantitative data available for at least one of our predefined outcomes. Meta-analysis was performed by the random-effects model using Stata software. RESULTS: Fifty studies of 203,288 patients were included. BAV patients had increased 30-day all-cause mortality (odds ratio [OR] = 1.23 [1.00-1.50], p = 0.05), in-hospital stroke (OR = 1.39 [1.01-1.93], p = 0.05), in-hospital and 30-day PPI (OR = 1.13 [1.00-1.27], p = 0.04; OR = 1.16 [1.04-1.13], p = 0.01) and in-hospital, 30-day and 1-year aortic regurgitation (AR) (OR = 1.48 [1.19-1.83], p < 0.01; OR = 1.79 [1.26-2.52], p < 0.01; OR = 1.64 [1.03-2.60], p = 0.04). Subgroup analysis on new-generation valves showed a reduced 1-year all-cause mortality (OR = 0.86 [CI = 0.75-0.98], p = 0.03), despite higher in-hospital and 30-day PPI (OR = 0.1.21 [1.04-1.41], p = 0.01; OR = 1.17 [1.05-1.31], p = 0.01) and in-hospital AR (OR = 1.62 [1.14-2.31], p = 0.01) in the BAV group. The quality of included studies was moderate-to-high, and only three analyses presented high heterogeneity. CONCLUSION: TAVR is associated with comparable outcomes in patients with BAV and TAV. Careful selection of BAV cases by preprocedural assessment of valve anatomy and burden of calcification, pre- and post-procedural dilation, and implementing newer generations of valves may improve the safety and efficacy of TAVR in BAV patients.

Nationwide Analysis of the Outcomes and Mortality of Hospitalized Infants with Concomitant Diagnosis of COVID-19.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) generally causes milder illness in the pediatric population. However, infants represent a higher-risk population with evolving symptomatology and severity. There is a paucity of large population-based data on the impact of COVID-19 on hospitalized infants. STUDY DESIGN: In this large cohort study, the National Inpatient Sample database was queried for all infant hospital admissions between January and December 2020 in the United States, with and without a diagnosis of COVID-19 based on ICD-10-CM U07. The mortality and morbidity of infants with and without COVID-19 were evaluated. Parent-reported race and outcomes were also analyzed. RESULTS: A weighted total of 3,754,236 infants who were hospitalized were identified, of which 4,265 patients (0.11%) had a concomitant diagnosis of COVID-19. Infants with COVID-19 had similar mortality and extracorporeal membrane oxygenation utilization. Infants with concomitant COVID-19 had a higher rate of respiratory failure, congestive heart failure, acute kidney injury, and coagulopathy. Compared with Caucasian infants and Asian infants, Hispanic and African American infants were more likely to have COVID-19 hospital admissions than hospitalizations without COVID-19 diagnosis. Patients with lower median household income represented the majority of the COVID-19 hospitalization. The infants with COVID-19 were more likely to have Medicaid or Medicare insurance and less likely to have private insurance. CONCLUSION: In this large cohort of hospitalized infants with COVID-19, the infection was associated with complications, including respiratory failure and endotracheal intubations but not associated with a higher risk for mortality. Infants from racial minorities and lower socioeconomic strata carry the highest burden of COVID-19 infection. KEY POINTS: · Infants with COVID-19 represent a higher-risk group with evolving symptomatology and severity.. · Infants with COVID-19 had similar mortality rates and extracorporeal membrane oxygenation utilization as those without COVID-19.. · Racial minorities and lower socioeconomic strata carry the highest burden of COVID-19 infection..

Evaluation and Management of Cardiac Sarcoidosis with Advanced Imaging.

A high clinical suspicion in the setting of appropriate history, physical exam, laboratory, and imaging parameters is often required to set the groundwork for diagnosis and management. Echocardiography may show septal thinning, evidence of systolic and diastolic dysfunction, along with impaired global longitudinal strain. Cardiac MRI reveals late gadolinium enhancement along with evidence of myocardial edema and inflammation on T2 weighted imaging and parametric mapping. 18F-FDG PET detects the presence of active inflammation and the presence of scar. Involvement of the right ventricle on MRI or PET confers a high risk for adverse cardiac events and mortality.

Gender-specific outcomes after percutaneous left atrial appendage closure: A nationwide readmission database analysis.

INTRODUCTION: Thromboembolism-associated stroke is the most feared complication of atrial fibrillation (AF). Percutaneous left atrial appendage closure (pLAAC) is indicated for stroke prevention in patients with AF who can not tolerate long-term anticoagulation. We aim to study gender differences in peri-procedural and readmissions outcomes in pLAAC patients. METHODS: Using the national readmission database from January 2016 to December 2018, AF patients undergoing the pLAAC procedure were identified. We used multivariate logistic regression analyses and time-to-event Cox regression analyses to conduct the study. Propensity matching with the Greedy method was done for the accuracy of results. RESULT: A total of 28 819 patients were included in our study. Among them 11 946 (41.5%) were women and 16 873 (58.6%) were men. The mean age of overall population was 76.1 ± 8.5 years, with women ~1 year older than men. The overall rate of complications was higher in women (8.6% vs. 6.6%, p < .001), primarily driven by bleeding-related complications, that is, major bleed (odds ratio [OR]: 1.32 95% confidence interval [CI]: 1.03-1.69, p = .029), blood transfusion (OR: 1.45, 95% CI: 1.06-1.97, p = .019), and cardiac tamponade (OR: 1.80, 95% CI: 1.13-2.89, p = .014). Women had two times higher peri-procedural ischemic stroke. There was no difference in peri-procedural mortality. Women remained at 20% and 13% higher risk for readmission at 30 days and 6 months of discharge. CONCLUSION: Women had higher peri-procedural complications and were at higher risk of readmissions at 30 days and 6 months. However, there was no difference in mortality during the index hospitalization. Further studies are necessary to determine causality.

Outcomes of rotational atherectomy followed by cutting balloon versus plain balloon before drug-eluting stent implantation for calcified coronary lesions: A meta-analysis.

OBJECTIVE: The aim of this study is to compare outcomes of rotational atherectomy and cutting balloon (RACB) versus rotational atherectomy and plain balloon (RAPB) before drug-eluting stent (DES) implantation in calcified coronary lesions. METHODS: Randomized controlled trials (RCT) and observational studies comparing RACB with RAPB were identified through a systematic search of published literature across multiple databases. Random effect meta-analysis was performed to compare the outcome between the two groups. RESULTS: Four studies were included in the meta-analysis (three observational and one RCT) involving a total of 315 patients. 166 patients had RACB, and 149 patients had RAPB before DES placement with a median follow-up of 11.5 months. Compared with patients who had RAPB there was no difference in MACE (composite of death, myocardial infarction, and target vessel revascularization) (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.25-2.18], slow flow/no reflow (OR: 0.71; 95% CI: 0.23-2.16), all-cause mortality (OR: 2.02; 95% CI: 0.28-14.60), and device success rate (OR: 1.79; 95% CI: 0.28-11.18) in the RACB approach. There was a benefit towards less target lesion revascularization in the RACB group; however, this outcome was reported in two studies (OR: 0.29; 95% CI: 0.08-0.99). On meta-regression there was no association between age, sex, diabetes, or lesion location with MACE and all-cause mortality. The studies were homogenous across all outcomes. CONCLUSION: RACB, as compared with RAPB, had a similar risk of MACE, all-cause mortality, device success, and complication, but a lower risk of target lesion revascularization.

Outcomes of Cardiac Arrest and Cardiopulmonary Resuscitation in Patients With Left Ventricular Assist Device; an Insight From a National Inpatient Sample.

BACKGROUND: Outcomes of patients with implanted left ventricular assist device (LVAD) implantation experiencing a cardiac arrest (CA) are not well reported. We aimed at defining the in-hospital outcomes of patients with implanted LVAD experiencing a CA. METHODS: The national inpatient sample (NIS) was queried using ICD9/ICD10 codes for patients older than 18 years with implanted LVAD and CA between 2010-2018. We excluded patients with orthotropic heart transplantation, biventricular assist device (BiVAD) implantation and do not resuscitate (DNR) status. RESULTS: A total of 93,153 hospitalisations between 2010 and 2018 with implanted LVAD were identified. Only 578 of these hospitalisations had experienced CA and of those, 173 (33%) hospitalisations underwent cardiopulmonary resuscitation (CPR). The mean age of hospitalisations that experienced a CA was 60.61±14.85 for non-survivors and 56.23±17.33 for survivors (p=0.14). The in-hospital mortality was 60.8% in hospitalisations with CA and 74.33% in hospitalisations in whom CPR was performed. In an analysis comparing survivors with non-survivors, non-survivors had more diabetes mellitus (DM) (p=0.01), and ischaemic heart disease (IHD) (p=0.04). Age, female sex, peripheral vascular disease and history of coronary artery bypass graft (CABG) were independently associated with increased mortality in our cohort. Also, ventricular tachycardia (VT) and CPR were independently associated with in-hospital mortality. During the study period, there was a significantly decreasing trend in performing CPR in LVAD hospitalisations with CA. CONCLUSION: In conclusion, age, female sex, peripheral vascular disease, history of CABG, VT and CPR were independently associated with in-hospital mortality in LVAD hospitalisations who experienced CA.

Readmission following urgent transcatheter aortic valve implantation versus urgent balloon aortic valvuloplasty in patients with decompensated heart failure or cardiogenic shock.

BACKGROUND: Urgent transcatheter aortic valve implantation (TAVI) is a feasible option for aortic stenosis (AS) patients with decompensated heart failure (HF) and cardiogenic shock (CS) as compared to the more traditional urgent balloon aortic valvuloplasty (BAV). OBJECTIVES: We conducted a retrospective analysis to compare risk and cause of readmission in these two high-risk groups. METHODS: Nationwide Readmission Database (NRD) 2011-2014 was retrospectively analyzed to identify patients with AS having either urgent TAVI or urgent BAV using appropriate ICD-9 codes. Propensity scores were used to match patients with urgent TAVI as compared to patients with urgent BAV. Statistical analysis was performed using the Stata 15.1 software. RESULTS: We identified a weighted sample of 6,670 patients with urgent BAV and 6,964 patients with urgent TAVI. The all-cause 30- and 90-day readmission was lower in the urgent TAVI group compared to urgent BAV (15.4 vs. 22.5%, (aHR): 0.92 [0.90-0.95] p < .001). 30-day readmission due to CV cause and HF was also lower in the urgent TAVI group (aHR, 0.93: p < .001 and aHR, 0.98: p = .040, respectively). The 30-day gastrointestinal (GI) bleed readmission rate was three times higher in urgent TAVI group (aHR, 3.00:95% CI (1.23-7.33), p = .016), but was not statistically significant at 90-days. Cardiac causes of readmission were the predominant cause of readmission in both groups, but more pronounced in urgent BAV group (60.3 vs. 40.5%, p < .001). CONCLUSION: Urgent TAVI appears beneficial in patients with AS and decompensated HF or CS driven by roughly 10 and 25% reductions in overall readmissions at 30 and 90 days, and marked reductions in reintervention, although offset partially by higher risk of readmission due to GI bleeding at 30 days.

30-day readmission following urgent and elective transcatheter aortic valve replacement: A Nationwide Readmission Database analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly used for decompensated severe symptomatic aortic stenosis. Data on urgent and elective TAVR readmission is scarce in the literature. Here, we have performed a retrospective cohort study with the Nationwide Readmission Database of 2016 to identify the rate of 30-day all-cause readmission, common causes of readmission, and distribution of morbidity in index admission and readmission after urgent and elective TAVR. METHODS: We used International Classification of Diseases, Tenth Revision codes (02R.F38H, 02R.F38Z, 02R.F48Z) for identification of all TAVR procedures done in 2016 in patients >18 years old. We found 8379 patients who underwent urgent TAVR and 32,006 patients who underwent elective TAVR in 2016. RESULT: The mean age of patients undergoing urgent TAVR was 79 ± 9.97 years with 44.6% women. The mean age of patients undergoing elective TAVR was 80.7 ± 8.25 years with 46.2% women. We found the 30-day all-cause readmission rate of 15.5% and 9.5% in patients undergoing urgent and elective TAVR, respectively (p < 0.001). The cardiac cause was the predominant cause of readmission in both groups (43.77% vs. 42.11%, p = 0.57), followed by pulmonary cause, gastrointestinal (GI) cause, and renal cause. Among cardiac causes, congestive heart failure (CHF) was predominant cause of readmission and was similar in both groups (18.73 in urgent TAVR vs. 15.73 in elective TAVR, p = 0.12). CONCLUSION: We found that the all-cause 30-day readmission rate was higher in patients who had undergone urgent TAVR. Further studies are needed to better understand this difference.

Periodontal Inflammation and the Risk of Cardiovascular Disease.

PURPOSE OF REVIEW: The role of oral bacteremia and periodontal inflammation driving atherosclerosis is still under investigation. This review article highlights the role of periodontal inflammation and oral microorganisms in the development and progression of atherosclerosis and cardiovascular diseases. RECENT FINDINGS: Association between periodontal and cardiovascular diseases has been well characterized, but causal correlation is yet to be established. For instance, untreated gingivitis can progress to periodontitis. Periodontal disease has been associated with several systemic diseases one of which is atherosclerosis. One possible association that was documented in literature is that poor oral hygiene leads to bacteremia, which in turn can cause bacterial growth over atherosclerotic coronary artery plaques and possibly worsen coronary artery disease. It is crucial that clinicians understand the association between periodontal and cardiovascular disease. A comprehensive treatment for periodontitis and re-establishment of a healthy periodontium can help in reduction of overall inflammation in the body. This may play an important role in prevention of cardiovascular disease, though future research is needed to establish this.

The impact of chronic kidney disease in women undergoing transcatheter aortic valve replacement: Analysis from the Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) registry.

BACKGROUND: The prevalence of both chronic kidney disease (CKD) and aortic stenosis (AS) increase with age. Although baseline CKD is frequent in patients undergoing transcatheter aortic valve replacement (TAVR), its significance among women is largely unknown. METHODS: Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) is a multinational, prospective registry of women undergoing TAVR for severe AS. We included patients with available baseline estimated glomerular filtration rate (eGFR) and completed 1-year follow-up. Patients were categorized into three groups based on their eGFR: No CKD (normal kidney function to stage 2 CKD: eGFR ≥60 ml/min/1.73 m2 ); (b) mild CKD (stage 3a CKD: eGFR = 45-59 ml/min/1.73 m2 ); and (c) moderate/severe CKD (stage ≥3b CKD: eGFR <45 ml/min/1.73 m2 ). All events were adjudicated according to the Valve Academic Research Consortium (VARC)-2 criteria. RESULT: Out of 852 women undergoing TAVR, 326 (38.3%) had no CKD, 225 (26.4%) had mild CKD, and 301 (35.3%) had moderate/severe CKD. Women with higher stage of CKD at baseline were more likely to have a history of hypertension, diabetes, atrial fibrillation, anemia, chronic lung disease, hemodialysis, prior percutaneous coronary intervention, and pacemaker implantation. After multivariate adjustment, moderate/severe CKD was associated with a greater risk of 1-year VARC-2 safety endpoints [hazard ratio (HR) 1.68, 95% confidence interval (CI): 1.10-2.60], all-cause death (HR 2.00, 95% CI: 1.03-3.90), and composite of death, myocardial infarction, stroke or life-threatening bleeding (HR 1.70, 95% CI: 1.04-2.76). There were no differences in 30-day and 1-year VARC-2 efficacy and 30-day VARC-2 safety outcomes. CONCLUSION: CKD is associated with substantial and independent risk for mortality and morbidity at 1-year follow-up in women undergoing TAVR.

Advances in the Pharmacogenomics of Antiplatelet Therapy.

BACKGROUND: Acute coronary syndrome (ACS) is a highly thrombotic state, and a sustained antiplatelet effect is vital to the prevention of thrombotic complications. Clopidogrel, the most widely used oral P2Y12 receptor antagonist in ACS, has attracted considerable attention because of significant variability in antiplatelet effect depending on the presence of CYP2C19 allele. Other P2Y12 receptor antagonists offer sustained and more predictable antiplatelet effects than clopidogrel albeit at an increased cost. Several studies have demonstrated the promising application of pharmacogenetics in choosing personalized antiplatelet therapy using the point-of-care genotype assays. AREAS OF UNCERTAINTY: Guidelines regarding the genotype-guided approach to the selection of antiplatelet therapy have been conflicting, and studies evaluating the effect of pharmacogenetic-guided selection of antiplatelet therapy on the outcomes have demonstrated mixed results. DATA SOURCES: A literature search was conducted using MEDLINE and EMBASE for studies reporting the association of pharmacogenetic-guided selection of antiplatelet therapy and the outcomes in patients with ACS until December 2018. RESULTS: Presence of specific CYP2C19 allele significantly influences clopidogrel metabolism and associated outcomes in patients with ACS. Thrombotic and bleeding complications are more common in patients with loss-of-function (LOF) and gain-of-function (GOF) alleles, respectively. Although the pharmacogenetic-guided approach to the selection of antiplatelet therapy appears promising in ACS, studies have shown conflicting results, and direct randomized evidence linking this approach with the better outcomes is lacking. CONCLUSIONS: Genotype-guided selection of antiplatelet therapy is expected to be useful in patients undergoing percutaneous coronary intervention (PCI) with a high risk of adverse outcomes. The patient-physician discussion should be an essential part of this decision-making process. Large-scale multicenter randomized controlled trials using the point-of-care genotype assay are needed to investigate this approach further before its use can be recommended in all comers.

Tachy-brady syndrome: Electrophysiology and evolving principles of management.

Sudden alterations in the heart rate may be associated with diverse symptoms. Sinus node dysfunction (SND), also known as sick sinus syndrome, is a sinoatrial (SA) node disorder. SND is primarily caused by the dysfunction of the pacemaker, as well as impaired impulse transmission resulting in a multitude of abnormalities in the heart rhythms, such as bradycardia-tachycardia, atrial bradyarrhythmias, and atrial tachyarrhythmias. The transition from bradycardia to tachycardia is generally referred to as "tachy-brady syndrome" (TBS). Although TBS is etiologically variable, the manifestations remain consistent throughout. Abnormal heart rhythms have the propensity to limit tissue perfusion resulting in palpitations, fatigue, lightheadedness, presyncope, and syncope. In this review, we examine the physiology of tachy-brady syndrome, the practical approach to its diagnosis and management, and the role of adenosine in treating SND.

Spontaneous coronary artery dissection outcomes among pregnant vs. non-pregnant women.

AIMS: Spontaneous coronary artery dissection (SCAD) has become increasingly recognized. It accounts for <1-4% of acute coronary syndrome presentations. Overall, however, it makes up over 40% of pregnancy-associated myocardial infarction. Furthermore, pregnancy-associated spontaneous coronary artery dissection (P-SCAD) is described to have a greater degree of clinical manifestations, including left ventricular dysfunction, shock, and left main or multivessel involvement. The findings are disconcerting, though many studies evaluating P-SCAD are based on case series data or are single centre studies. METHODS AND RESULTS: The aim of this study was to evaluate a larger national dataset to evaluate the outcomes of SCAD and specifically P-SCAD in an attempt to better characterize the severity and clinical nature of this condition. To conduct this study, we analysed the National Readmission Database from January 2016 to December 2020. Propensity matching was done using the Greedy 1:1 method. Multivariate logistics and time-to-event Cox regression analysis models were built by including all confounders significantly associated with the outcome on univariable analysis with a cut-off P-value of 0.2. In multivariate regression analysis, P-SCAD patients had a non-propensity matched odds ratio (OR) of 0.21 (0.3-1.54, P = 0.123) of dying and a propensity matched OR of 0.11 (0.02-0.61, P = 0.012) of dying. Thirty-day readmission rate for P-SCAD was 15.8% (n = 93) and for non-pregnant spontaneous coronary artery dissection (NP-SCAD) was 11.2% (n = 2286); non-propensity matched OR for readmission for PSCAD patients was 1.68 (1.24-2.29, P = 0.001) and propensity matched OR was 3.39 (1.93-5.97, P < 0.001). CONCLUSION: Among hospitalized patient, P-SCAD was associated with similar clinical outcomes and reduced incidence of death when compared with NP-SCAD, though had higher rates of 30-day readmission. Larger-scale observational data will be needed to ascertain the true incidence of cardiovascular complications as it relates to P-SCAD.

Outcomes and Readmissions after Left Atrial Appendage Occlusion in Octogenarians: A Contemporary Analysis.

INTRODUCTION AND OBJECTIVES: The outcomes of left atrial appendage occlusion (LAAO) with the Watchman device in octogenarians are unknown as this population was underrepresented in major clinical trials. This study aims at examining the causes and outcomes of readmission after LAAO. DESIGN: A retrospective cohort study based on the National Readmission Database in the United States. SETTINGS AND PARTICIPANT: Patients aged ≥80 years, admitted between January 2016 and December 2018, with the primary diagnosis of atrial fibrillation or flutter or who had LAAO were included in the study. Patients who died during index admission were excluded. METHODS: We used the National Readmission Database and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify study participants. Data analysis was performed through Stata, version 17. Univariate and multivariate aggression analysis was used to adjust for confounders using Student t tests and χ2 tests. RESULTS: We identified 491,329 patients on anticoagulation (AC) and 2030 patients who underwent LAA closure. Neither group differed regarding hypertension, previous myocardial infarction, or valvular heart disease. All-cause readmissions were lower in the LAAO group at 45 days (adjusted P < .01). All-cause readmissions at 45 and 90 days were similar in both groups. There was an increase in gastrointestinal bleeding (GIB) readmissions in the LAAO at 45 (P < .01), 90 (P < .01), and 180 (P < .01) days. There was no difference in GIB readmission between the 2 groups. There was no also difference in stroke or intracranial hemorrhage rates between the 2 groups throughout the follow-up period. CONCLUSION AND IMPLICATIONS: In octogenarians who received LAAO, the rate of GIB increased during the first 6 months after the procedure; however, it was not different from that of AC after that. Special attention should be given to the antithrombotic regimens after LAAO to avoid bleeding in this vulnerable patient population.

Association between testosterone replacement therapy and cardiovascular outcomes: A meta-analysis of 30 randomized controlled trials.

BACKGROUND: The Cardiovascular safety of testosterone replacement therapy (TRT) among men with hypogonadism is not well established to date. Hence, we sought to evaluate the cardiovascular disease (CVD) outcomes among patients receiving testosterone therapy by using all recently published randomized controlled trials. METHODS: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until September 30th, 2023. RESULTS: A total of 30 randomized trials with 11,502 patients were included in the final analysis. The mean age was ranging from 61.61 to 61.82 years. Pooled analysis of primary and secondary outcomes showed that the incidence of any CVD events (OR, 1.12 (95%CI: 0.77-1.62), P = 0.55), stroke (OR, 1.01 (95%CI: 0.68-1.51), P = 0.94), myocardial infarction (OR, 1.05 (95%CI: 0.76-1.45), P = 0.77), all-cause mortality (OR, 0.94 (95%CI: 0.76-1.17), P = 0.57), and CVD mortality (OR, 0.87 (95%CI: 0.65-1.15), P = 0.31) was comparable between TRT and placebo groups. CONCLUSION: Our analysis indicates that for patients with hypogonadism, testosterone replacement therapy does not increase the CVD risk and all-cause mortality.