Quadricuspid aortic valve (QAV) is a congenital heart anomaly in which the aortic valve has four cusps of various size possibilities, as opposed to the three symmetrical cusps generally observed. This cardiac valvular abnormality is rarely identified, with an estimated incidence rate of 0.013% to 0.043%, although recent technological advancements in diagnostics have contributed to an increase in detection. Historically, it had been typically encountered during open heart surgery or postmortem; however, it is presently diagnosed primarily via ultrasound echocardiography, and could go undetected unless specifically considered. It was first reported by Babington in 1847, and since then approximately 300 cases have been published. This condition is sporadically associated with additional congenital cardiovascular defects, with coronary artery irregularities being the most common. In more than half of published QAV incidences it has led to the progressive development of aortic regurgitation (AR) usually sans aortic stenosis, particularly amongst elderly patients, often requiring surgical intervention after 50 years of age. A fifth of total instances, but two-thirds of instances with AR, warrant surgery seldom amidst complications, with reconstructive tricuspidization preferred over valve replacement.

Protein sequences encode both structure and foldability. Whereas the interrelationship of sequence and structure has been extensively investigated, the origins of folding efficiency are enigmatic. We demonstrate that the folding of proinsulin requires a flexible N-terminal hydrophobic residue that is dispensable for the structure, activity, and stability of the mature hormone. This residue (Phe B1 in placental mammals) is variably positioned within crystal structures and exhibits 1 H NMR motional narrowing in solution. Despite such flexibility, its deletion impaired insulin chain combination and led in cell culture to formation of non-native disulfide isomers with impaired secretion of the variant proinsulin. Cellular folding and secretion were maintained by hydrophobic substitutions at B1 but markedly perturbed by polar or charged side chains. We propose that, during folding, a hydrophobic side chain at B1 anchors transient long-range interactions by a flexible N-terminal arm (residues B1-B8) to mediate kinetic or thermodynamic partitioning among disulfide intermediates. Evidence for the overall contribution of the arm to folding was obtained by alanine scanning mutagenesis. Together, our findings demonstrate that efficient folding of proinsulin requires N-terminal sequences that are dispensable in the native state. Such arm-dependent folding can be abrogated by mutations associated with ␤-cell dysfunction and neonatal diabetes mellitus.The efficiency of protein folding poses a fundamental problem at the intersection of biophysics, cell biology, and medicine (1, 2). Because the existence of a unique and accessible ground state is unrepresentative of polypeptides as a class of heteropolymers, foldability is an evolved property of biological sequences (3). Current kinetic models envisage a funnel-shaped free-energy landscape, enabling multiple trajectories to the native state (4 -6). What distinguishes foldable from non-foldable sequences (7), and how are bottlenecks avoided (8 -10)? The salience of these questions has been reinforced by recognition of proteotoxicity as a general pathological mechanism underlying diverse diseases (11,12). Here, we describe a cryptic folding element in a protein that is dispensable once the native state has been reached.A model is provided by insulin, a globular protein central to the regulation of vertebrate metabolism (13). Its impaired biosynthesis causes ␤-cell dysfunction and permanent neonatalonset diabetes mellitus (DM) 4 (14 -17). The insulin gene encodes a single-chain precursor, preproinsulin (Fig. 1A, top) (18). A signal peptide (gray bar) is cleaved on translocation into the endoplasmic reticulum (ER) to yield proinsulin. The precursor contains successive sequence motifs, defining B, C, and A domains (blue, black, and red , respectively, in Fig. 1A) (19). Whereas the translocated polypeptide is reduced and unfolded, oxidative folding in the ER yields a well organized A-B (insulinlike) core and disordered C-domain (dashed black segment in Fig. 1B) (20 -26). Folding is ...

A 43-year-old man with an unremarkable medical history presented to our hospital with 2 weeks of headaches, ataxia and confusion. CT of the head revealed a large haemorrhagic cystic lesion. A subsequent chest CT revealed a large left atrial mass. The mass was subsequently biopsied with positive immunohistochemistry staining for MDM2, FLI1 and vimentin. Real-time PCR revealed MDM2 amplification, confirming the diagnosis of intimal sarcoma. The patient underwent surgical resection and reconstruction of the atrium with subsequent discharge to short-term rehabilitation, but his symptoms continued to progress. A repeat CT of the head revealed a new cerebellar mass. He underwent a second resection, but continued to experience worsening symptoms. He was diagnosed with stage IV intimal sarcoma and referred to hospice. The patient died 5 months after initial presentation. Autopsy was performed and revealed the cause of death as pneumonia. There was no involvement of the pulmonic or aortic vessels.

Electronic cigarettes may increase the risk of long-term cardiovascular morbidity. To protect the heart, awareness should be raised of the risks and limits of E-cigarette aerosol exposure. Thus, this systematic review and meta-analysis assessed the cardiovascular risk of e-smoking. This systematic review was conducted by using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched PubMed, Embase, Scopus, Web of Science, and Science Direct databases in December 2022 to identify studies investigating e-cigarettes' impact on the heart. The study was supported by meta-analysis and qualitative review. Out of the initial 493 papers, only 15 met the inclusion criteria and were included in the study. The cumulative number of participants in the myocardial infarction (MI) group was 85,420, and in the sympathetic groups in whom the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR) were measured, were 332 cigarette smokers. The control group included the “never use,” “non-smokers,” and “never smoke.” The pooled analysis showed a significant difference between the e-cigarette smokers and the control group regarding the risk of developing MI in former smokers (OR= 0.12; 95% CI: 0.01-1.72, P = 0.12) and never smoked (OR= 0.02; 95% CI: 0.00-0.44, P = 0.01) favoring the control group. The pooled analysis of the included studies showed a significant difference between the e-cigarette smokers with nicotine and the control group regarding the mean difference (MD) of the SBP (MD = 2.89; 95% CI: 1.94-3.84; P < 0.001), the DBP (MD = 3.10; 95% CI: 0.42-5.78; P = 0.02), the MBP (MD = 7.05; 95% CI: 2.70-1.40; P = 0.001), and HF (MD = 3.13; 95% CI: 0.96-5.29; P = 0.005) favoring the control group. We conclude that using e-cigarettes has a detrimental effect on cardiac health. The risk of severe cardiac conditions increases with e-cigarettes. Thus, vaping can do more harm than good. Consequently, the misleading notion that e-cigarettes are less harmful should be challenged.

Introduction: Acute Decompensated Heart Failure is one of the most common reasons for hospitalization in the United States. Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure admissions, significant contribution owing to various co-morbidities. The role of kidney impairment on admission and prognostic association with early HFpEF readmission is unclear. Methods: We conducted a retrospective analysis of patients admitted with decompensated HFpEF at a hospital in New York City. Clinical demographics & admission laboratory values collected to classify kidney function, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate glomerular filtration rate (GFR). Severe renal impairment (SRI), defined as a GFR less than 15 mL/min/1.73 m 2 . Patients followed for one-year to assess all-cause & cardiac-specific readmission within 30 days & all-cause mortality within one year. Results: A total of 358 patients with HFpEF were studied, 218 (60.8%) were female, 196 (54.6%) with diabetes. There were 82 readmissions (22.9%) within 30 days, 37 (10.3%) due to cardiac-specific causes, 69 (19.3%) who died within one year of hospitalization. There were 47 (13.1%) who met criteria of SRI on admission. No difference in one-year mortality with SRI, compare to normal renal function (38.2% vs. 23.1%, p = 0.416). Patients with SRI were more likely to be readmitted within 30-days for cardiac specific reasons than normal renal function (27.6% vs. 8.5%, p = 0.034), while a borderline significant increase in all-cause readmission (38.2% vs. 23.1%, p = 0.066). Conclusions: Patients with HFpEF & SRI, were more likely to experience readmission within 30 days due to cardiac-specific reasons than patients with normal renal function. These findings may assist in enhancing cardiac-specific prevention strategies in discharge planning.

Background: The H2FPEF score is a validated scoring system to determine whether dyspnea may be due to heart failure with preserved ejection fraction (HFpEF). Recent evidence has suggested that H2FPEF scoring system may correlate with outcomes in established HFpEF. Its utilization for estimating mortality in patients who die within one year of discharge is not known. Methods: We collected clinical demographics and echocardiographic parameters from reports to calculate H2FPEF scores for 301 patients admitted with decompensated HFpEF between August 2016 and 2017. Patients were included if an echocardiographic report was available within 3 months, confirming an ejection fraction > 50%. E/E’ and filling pressures were scored as 0 if not recorded in the echocardiographic report. Results: Median age was 81 years (IQR: 71-89), with 62.9% female. One-year follow-up was confirmed for 268 patients, with 56 deaths (20.9%). Receiver operating curve analysis suggest borderline significance of H2FPEF in predicting one-year mortality (area under curve, 0.576, 95% CI: 0.493-0.658, p=0.073). Optimal H2FPEF cutpoint score was 4.5 (73% sensitivity, 50% specificity). On univariate analysis, body mass index (BMI) > 30, hypertension, atrial fibrillation (p<0.001) and pulmonary artery systemic pressure > 35 mmHg (p=0.038) were associated with one-year mortality. On stepwise logistic regression, only BMI > 30 and atrial fibrillation remained associated with mortality in multivariate analysis. Conclusion: The utilization of H2FPEF in established HFpEF might confer some ability to predict one-year mortality, driven by obesity (2 points) and atrial fibrillation (3 points). Validation in larger cohorts with longer follow-up is necessary to establish its potential role in discharge planning and transitions of care of decompensated HFpEF.

Introduction: The utility of pre-procedure statins prior to coronary angiography has been utilized as an adjunct in the prevention of contrast-induced nephropathy (CIN). This has been attributed to the pleotropic and anti-inflammatory effects of the statin. Whether there is a dose and intensity dependent effect on the prevention of CIN is unknown. Methods: We performed a hierarchical network meta-analysis on all published randomized-controlled trials up to March 2020 to determine whether high-intensity atorvastatin (40mg or 80mg) was superior to lower intensity atorvastatin (20mg or less) and high-intensity or low-intensity statins. We searched PubMed, MEDLINE, Embase, Web of Science and Cochrane database for randomized-controlled studies without restriction to language. Studies published in Chinese was translated using Google Translate. Network meta-analysis was performed using NetMetaXL version 1.6.1. Results: We analyzed 49 trials, comprised of 13,395 patients, comparing five arms of treatment: Moderate/High intensity atorvastatin, Low intensity atorvastatin, Moderate/High intensity other statin, Low intensity other statin and None. There were 1,029 events for CIN (7.68%). In pairways comparisons, Moderate/High intensity atorvastatin reduced CIN by 0.70 (95% CI: 0.54-0.91) when compared to placebo. When compared to Moderate/High intensity other statins, the difference was not statistically significant (95% CI: 0.50-1.08). Conclusion: Moderate to High Dose Atorvastatin was not superior to other statins in prevention of CIN. Further investigation into the anti-inflammatory properties of statins may be helpful in understanding the role of statins as adjunct treatment to standard of care in preventing CIN.

Introduction: Heart Failure is one of the leading causes of readmission in the United States. Heart Failure with preserved Ejection Fraction (HFpEF) accounts for a growing proportion of heart failure hospitalizations and accounts for approximately half of hospitalizations today. Unlike Heart Failure with reduced Ejection Fraction (HFrEF), there are no consensus-driven guidelines for the management of HFpEF. Methods: We collected demographic data, co-morbidities, laboratory and echocardiographic data on patients hospitalized with HFpEF throughout our health care system between August 2016 to August 2017. We assessed length of stay (LOS), whether the patient was re-admitted for any cause within 30 days and whether the patient died within 1 year of index hospitalization. We performed a Wilcoxon rank-sum test comparing patients who were both readmitted within 30 days for any reason and died within 1 year, against patients who were readmitted but were verified alive at one-year follow-up. Results: There were 366 patients hospitalized for HFpEF during the study period. Overall 30-day readmission rate was 24.3%, with a one-year mortality of 19.9%. One-year outcomes was verifiable for 359 patients. There were 27 patients who were readmitted within 30 days and died within one year of follow-up. Median LOS was significantly greater in patients during index hospitalization who died within 1 year of follow-up (Median LOS: 8 days, IQR 5-10 days), compared to patients who were readmitted within 30 days, but were alive at 1-year follow-up (Median LOS: 5 days, IQR: 3-8 days; p-value = 0.001). Conclusions: Among patients who were re-hospitalized within 30 days of an index hospitalization for HFpEF, LOS was significantly greater than patients who died within one year, compared to patients who remained alive at one-year follow-up. This may help identify a high-risk subset on index hospitalization and assist care transition teams and primary care physicians at follow-up in regarding discussions on goals of care and life sustaining treatments.