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.

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.

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.

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.

In-hospital complications after MitraClip in patients with heart failure and preserved versus reduced ejection fraction in the United States.

BACKGROUND: The clinical benefits of transcatheter edge to edge mitral valve repair have been well established in patients with heart failure and severe mitral regurgitation (MR) who have prohibitive surgical risk. In March of 2019, the FDA approved the MitraClip for treatment of selected patients with HF and severe secondary MR. However, the relative outcomes of patients with HFrEF and HFpEF treated with MitraClip are largely unknown. We therefore sought to investigate the incidence and characteristics of in-hospital mortality in patients with HFpEF and HFrEF following MitraClip. METHODS: The study sample analyzed was originated from the National Inpatient Sample (NIS) registry which includes data from hospitalized patients in the United States (US) between January 1, 2012 and December 31, 2020. Data were extracted from the entire NIS registry using ICD-9 codes. Patients with the primary or secondary diagnosis of MitraClip were identified. Hospitalizations for HFpEF and HFrEF were identified based on ICD-9-CM and ICD-10-CM codes. Demographics, conventional risk factors, and in-hospital outcomes were evaluated. RESULTS: 23,260 hospitalizations for MitraClip implantation between 2016 and 2020 were analyzed. The HFrEF group had higher absolute rates of complications as well as a higher observed in-hospital mortality (2.4 % vs 1.7 %; OR 0.75 95 % CI 0.44-1.26; p 0.28) which did not meet statistical significance. Absolute rates of acute myocardial infarction (AMI), acute kidney injury (AKI) and respiratory failure necessitating invasive mechanical ventilation were observed to be higher among HFrEF patients. Post-procedural shock was significantly more common in patients with HFrEF (9.0 % vs 2.8 %: OR 0.34 95 % CI 0.25-0.48 p < 0.001). Significantly longer hospitalizations were observed in the HFrEF cohort (5.3 ± 11.2 days vs 4.2 ± 7.3 days; p < 0.001) as well as a higher total hospitalization cost (61,723 ± 56,728 USD vs 57,278 ± 46,143). CONCLUSIONS: In the present study of US patients, those with HFrEF were observed to have statistically higher risk of in-hospital post-procedural shock and longer hospitalization length of stay when compared with patients with HFpEF who underwent MitraClip implantation. Additionally, patients with HFrEF undergoing MitraClip procedure were observed to have higher absolute rates of certain post-procedural complications, however these observations did not reach statistical significance. Understanding of the aforementioned differences after MitraClip implantation may be useful in-patient selection, prognostic guidance, and hypothesis generation to propel future large clinical studies.

Cardioprotective effect of antiviral therapy among hepatitis C infected patients: A meta-analysis.

Background: Hepatitis C (HCV) infections have been shown to be associated a with higher risk of atherosclerotic cardiovascular disease (CVD). However, the use of antiviral therapy (AVT) and the risk of CVD has not been well established with limited literature. Objective: We sought to evaluate the association between AVT use post-HCV infection and cardiovascular outcomes. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th March 2023. Primary clinical outcomes were the incidence of any CVD. Secondary endpoints were all-cause of mortality, stroke, myocardial infarction, and peripheral artery disease. Results: A total of 394,452 patients were included in the analysis (111,076 in the AVT group and 283,376 patients in the NAVT group). The mean age of patients among AVT and NAVT groups was comparable (58.7 vs 58.18). The pooled analysis of primary outcomes showed that AVT was associated with a significantly reduced risk of any CVD (HR, 0.55(95%CI: 0.41-0.75), P < 0.001) compared with the NAVT group of patients. Secondary outcomes including ACM (HR, 0.38(95%CI: 0.32-0.46), P < 0.001), MI (HR, 0.62(95%CI: 0.41-0.94), P = 0.02), and PAD (HR, 0.62(95%CI: 0.41-0.93), P = 0.02) were significantly lower among AVT groups compared with NAVT groups of patients with HCV infection. However, the risk of stroke was comparable between both groups of patients (HR, 0.79(95%CI: 0.58-1.07), P = 0.13). Conclusion: Our analysis shows HCV-infected patients post-AVT have a significantly lower risk of any CVD, MI, ACM, and PAD compared with NAVT groups of patients.

Ultrasound Guidance for Vascular Access for Coronary Angiogram: A Meta-Analysis of Randomized Controlled Trials.

Obtaining vascular access during percutaneous coronary intervention is necessary to facilitate the procedure but carries procedural risks that impact patient outcomes. Historically, vascular access has been accomplished using anatomic landmarks, pulsation, and/or fluoroscopic guidance. Ultrasound (US) guidance has emerged as a modality for achieving vascular access in a multitude of interventional procedures including those in the cardiac catheterization laboratory. US use has been demonstrated in randomized controlled trials and meta-analyses to be associated with an increased success rate for vascular access with fewer complications, although the data are mixed. We aimed to re-evaluate the totality of evidence in an updated meta-analysis to compare the ease of access and complications rates between US-guided and manual vascular access. A meta-analysis of 8 randomized controlled trials including 5,170 patients was performed. The primary outcome evaluated was the rate of access failure, and the secondary outcomes included hematomas and access site bleeding. US-guided arterial access was associated with a significantly higher rate of first-attempt success and a decreased risk of venipuncture. US use had a trend toward a lower total number of attempts, but the results were not significant. This updated meta-analysis further supports the use of US for vascular access for coronary angiography because of higher rates of first-attempt success and reduced venipuncture. However, there was no significant difference in vascular complications such as hematoma, pseudoaneurysm, and bleeding complications. Because of the high morbidity of bleeding complications associated with coronary angiography, further research should be done to reduce these complications.

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.

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..

Dispelling the Saddle Pulmonary Embolism Myth (from a Comparison of Saddle Versus Non-Saddle Pulmonary Embolism).

In the setting of an acute pulmonary embolism (PE), there is often an assumed association between a saddle PE (SPE) and increased clinical severity. We aimed to determine the magnitude of SPE proximal pulmonary artery (PA) flow obstruction and its impact on right ventricular (RV) function in the setting of acute PE in a single-center series. From 2005 to 2022, patients with acute PE presenting with acute RV dysfunction requiring intervention were classified as SPE and non-SPE based on presenting computed tomography (CT) scans. SPE flow obstruction was determined by the ratio of the orthogonal cross-sectional surface area measurements of clot and native PA at the location of maximum clot burden in the right PA and left PA. Presenting RV function based on clinical and imaging parameters (CT and transthoracic echocardiography) were compared between SPE and non-SPE cohorts. A total of 174 patients were identified (SPE 92 [52.9%] and non-SPE 82 [47.1%]). Demographics and co-morbidities were similar. In patients with SPE, there was a mean 25.9% total flow obstruction (right PA 26.9% and left PA 25.5%). Non-SPE had greater clinical RV dysfunction on presentation as reflected by more high-risk PE (43.9% vs 26.1%, p = 0.01), need for venoarterial extracorporeal membrane oxygenation (21.9% vs 10.9%, p = 0.05), and more preoperative cardiopulmonary resuscitation (16.7% vs 7.8%, p = 0.08). RV:left ventricular ratio (CT and transthoracic echocardiography) and RV fractional area change were statistically similar between groups. In-hospital mortality was statistically similar between cohorts (4.9% non-SPE vs 2.1% SPE, p = 0.32). In conclusion, in a single-center series of patients with acute PE with RV dysfunction, SPE did not cause proximal flow-limiting obstruction. Non-SPE was associated with more clinical RV dysfunction than SPE. Thus, it should not be assumed that a non-SPE is a marker of patient stability.

Integrative Genetic Approach Facilitates Precision Strategies for Acute Myocardial Infarction.

Acute myocardial infarction remains a significant cause of mortality worldwide and its burden continues to grow. Its pathophysiology is known to be complex and multifactorial, with several acquired and inherited risk factors. As advances in technology and medical therapy continue, there is now increasing recognition of the role that genetics play in the development and management of myocardial infarction. The genetic determinants of acute coronary syndrome are still vastly understudied, but the advent of whole-genome scanning and genome-wide association studies has significantly expanded the current understanding of genetics and simultaneously fostered hope that genetic profiling and gene-guided treatments could substantially impact clinical outcomes. The identification of genes associated with acute myocardial infarction can help in the development of personalized medicine, risk stratification, and improved therapeutic strategies. In this context, several genes have been studied, and their potential involvement in increasing the risk for acute myocardial infarction is being investigated. As such, this article provides a review of some of the genes potentially related to an increased risk for acute myocardial infarction as well as the latest updates in gene-guided risk stratification and treatment strategies.

Aortic Stenosis Phenotypes and Precision Transcatheter Aortic Valve Implantation.

Patients with a clinical indication for aortic valve replacement can either undergo surgical aortic valve replacement (SAVR) or Transcatheter Aortic Valve Implantation (TAVI). There are many different factors that go into determining which type of replacement to undergo, including age, life expectancy, comorbidities, frailty, and patient preference. While both options offer significant benefits to patients in terms of clinical outcomes and quality of life, there is growing interest in expanding the indications for TAVI due to its minimally invasive approach. However, it is worth noting that there are several discrepancies in TAVI outcomes in regards to various endpoints, including death, stroke, and major cardiovascular events. It is unclear why these discrepancies exist, but potential explanations include the diversity of etiologies for aortic stenosis, complex patient comorbidities, and ongoing advancements in both medical therapies and devices. Of these possibilities, we propose that phenotypic variation of aortic stenosis has the most significant impact on post-TAVI clinical outcomes. Such variability in phenotypes is often due to a complex interplay between underlying comorbidities and environmental and inherent patient risk factors. However, there is growing evidence to suggest that patient genetics may also play a role in aortic stenosis pathology. As such, we propose that the selection and management of TAVI patients should emphasize a precision medicine approach.

Acute myopericarditis due to human granulocytic anaplasmosis.

We present a case of a 54-year-old gentleman with a history of hypertension and chronic HIV who presented with fever and epigastric pain, found to have elevated troponin-I levels and diffuse ST-segement elevations on ECG without clinical evidence of ischemia concerning for myopericarditis. Initial laboratory findings also included thrombocytopenia and elevated aminotransferases as well as computed tomography imaging revealing splenic infarcts. Given plausible exposure to ticks, this led to the eventual diagnosis of anaplasmosis confirmed on PCR assay. Cardiac MRI images confirmed myocardial involvement, which resolved with antibiotic treatment. While rare, cardiac involvement is possible sequelae of anaplasmosis infection as illustrated by this case.

Role of Influenza Vaccination in Cardiovascular Disease: Systematic Review and Meta-Analysis.

Influenza vaccination has shown great promise in terms of its cardioprotective effects. The aim of our analysis is to provide evidence regarding the protective effects of influenza vaccination in patients with cardiovascular disease. We conducted a systematic literature search to identify trials assessing the cardiovascular outcomes of influenza vaccination. Summary effects were calculated using a DerSimonian and Laird fixed effects and random effects model as odds ratio with 95% confidence intervals (CIs) for all the clinical endpoints. Fifteen studies with a total of 745,001 patients were included in our analysis. There was lower rates of all-cause mortality [odds ratio (OR) = 0.74, 95% CI 0.64-0.86], cardiovascular death (OR = 0.73, 95% CI 0.59-0.92), and stroke (OR = 0.71, 95% CI 0.57-0.89) in patients who received the influenza vaccine compared to placebo. There was no significant statistical difference in rates of myocardial infarction (OR = 0.91, 95% CI 0.69-1.21) or heart failure hospitalizations (OR = 1.06, 95% CI 0.85-1.31) in the 2 cohorts. In patients with cardiovascular disease, influenza vaccination is associated with lower all-cause mortality, cardiovascular death, and stroke.

Trends in the Prevalence of Infiltrative Cardiomyopathy Among Patients With in-Hospital Cardiac Arrest.

Sarcoidosis, amyloidosis, hemochromatosis and scleroderma are the most forms of infiltrative/nonischemic cardiomyopathy (NICM) associated with sudden cardiac death. In patients who undergo in-hospital cardiac arrest, a high index of suspicion is required to rule out NICM as an underlying contributor. We aimed to analyze the prevalence of NICM among patients with in-hospital cardiac arrest and identify factors associated with increased mortality. We analyzed data from the National Inpatient Sample, and identified patients who were hospitalized across 10 years from 2010 to 2019 with a diagnosis of cardiac arrest and NICM. The total number of patients with in-hospital cardiac arrest was 19,34,260. The total number with NICM was 14,803 (0.77%). Mean age was 63 years. Overall prevalence of NICM across the years ranged between 0.75% to 0.9%, with a significant temporal increase (P < 0.01). Incidence of in-hospital mortality ranged between 61% to 76% for females and 30% to 38% for males. The following comorbidities were more prevalent in patients with NICM than those without: heart failure, chronic obstructive pulmonary disease (COPD), chronic kidney disease, anemia, malignancy, coagulopathy, ventricular tachycardia, acute kidney injury and stroke. The following factors were independent predictors of in-hospital mortality-age, female gender, Hispanic race, history of COPD and presence of malignancy (P = 0.042). The prevalence of infiltrative cardiomyopathy in patients with in-hospital cardiac arrest is increasing. Females, older patients and Hispanic population are at an increased risk of mortality. Sex and race-based disparities in the prevalence of NICM in patients with in-hospital cardiac arrest is an area of further research.