Comparison of MANTA versus Perclose Prostyle large-bore vascular closure devices during transcatheter aortic valve implantation.

BACKGROUND: New vascular closure devices (VCD) are being introduced for achieving hemostasis after transcatheter aortic valve implantation (TAVI). However, no safety or efficacy data have been published compared to other contemporary VCD. AIM: To compare the safety and efficacy of suture-based Perclose Prostyle as compared to plug-based MANTA device. METHODS: A total of 408 consecutive TAVI patients from two high volume TAVI centers were included in the present study. Patients were grouped according to VCD: Prostyle versus MANTA. Propensity score matching (PSM) and multivariable analysis were utilized to compare clinical endpoints between the two groups. The primary endpoint was any vascular complication (VC) according to VARC-3 criteria. RESULTS: After PSM, a total of 264 patients were analyzed, of them 132 in each group. Overall baseline characteristics of the two groups were comparable. Primary end-point was similar between MANTA as compared to Prostyle (16.7% vs. 15.3% respectively, p = 0.888). The main driver for VC among MANTA group were minor vascular complications (15.2%). Conversely, minor and major VC contributed equally to the primary endpoint among Prostyle group (7.6%) (p = 0.013). No outcome predictors were identified in multivariate analysis. CONCLUSIONS: VCD for transfemoral TAVI using the new-generation Prostyle device or the MANTA device achieved comparable VARC-3 VC rates.

The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices.

BACKGROUND: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2-I) in patients with left ventricular assist devices (LVAD) are unknown. METHODS: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2-I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2-I. RESULTS: SGLT2-I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2-I initiation was 108 days, IQR (26-477). Following SGLT2-I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2-38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7-4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23-11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2-I initiation (p > 0.2 for all). No adverse events were recorded during median follow-up of 354 days, IQR (206-786). CONCLUSION: SGLT2-I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.

Amyloid Typing in Cardiac Amyloidosis Using Western Blotting.

BACKGROUND: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA). OBJECTIVES: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context. METHODS: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data. RESULTS: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS. CONCLUSIONS: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.

The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study.

BACKGROUND: As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. METHODS: A retrospective, pharmacovigilance study of the FDA's global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR). RESULTS: We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (Pinteraction threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults. CONCLUSION: In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.

Investigation of cardiac arrhythmia events in patients treated with lamotrigine: FDA adverse event reporing system analysis.

OBJECTIVES: In October 2020 and March 2021, the U.S. Food and Drug Administration (FDA) classified lamotrigine as a class IB antiarrhythmic, announcing an increased risk of heart rhythm problems. We sought to investigate the nature of the arrhythmia signal with lamotrigine use compared to anticonvulsants with sodium-blocking and non-sodium-blocking mechanisms. METHODS: This retrospective pharmacovigilance case-non-case study used disproportionality analysis to detect signals of adverse reaction of interest reported with lamotrigine to the FDA Adverse Event Reporting System (FAERS) between 1998 and 2022. Our regression model adjusted for interacting concomitant medications. Sensitivity analyses included stratifying by indication and publication date. RESULTS: Overall, 2917 cases of heart rhythm problems with anticonvulsants were analyzed (1557 female [58.4%] and 1109 male [41.6%]). The mean age ± standard deviation (SD) was 43 ± 19, the groups did not differ significantly by age. Forty cases (7.91%) in the epileptic indication included more than one concomitant medication that influences cardiac conduction. The disproportionality signal for cardiac arrest did not differ for lamotrigine compared with other anticonvulsants, adjusted reporting odds ratio (adj.ROR, .88; 95% CI, .59-1.29) in the epileptic indication. A significantly lower reporting risk for bradyarrhythmia was identified with lamotrigine users in the epileptic population, (adj.ROR, .45; 95% confidence interval [CI], .29-.68). The psychiatric indication demonstrated a sixfold reporting risk for cardiac arrest compared to the epileptic indication. Concomitant medications that affect cardiac conduction, as well as reports on overdose and suicide attempts, were significant variables in psychiatric patients (ROR, 2.45; 95% CI, 2.21-2.71) and (ROR, 1.44; 95% CI, 1.34-1.55), respectively. SIGNIFICANCE: Our results do not support a significant difference in the reporting risk for cardiac arrest, syncope, tachyarrhythmia, and bradyarrhythmia with lamotrigine in the epileptic indication. Signals of cardiac arrest in lamotrigine could be explained by confounding factors in the psychiatric indication, such as greater concomitant use of medications with cardiac adverse events, and greater reports on overdose and suicide attempts. We recommend that patients with polypharmacy undergo clinical and electrocardiographic monitoring. We illustrate the importance of examining signals for separate indications.

Differential effect of high-frequency electroporation on myocardium vs. non-myocardial tissues.

AIMS: Pulsed-field ablation (PFA) is an emerging non-thermal ablation method based on the biophysical phenomenon of electroporation. Data on PFA cardiac selectivity nature and tissue-specific thresholds are lacking. We aim to compare the in vivo differential effect of high-frequency irreversible electroporation (HF-IRE) protocols on various tissues. METHODS AND RESULTS: Twenty-three Sprague-Dawle rodents were allocated into three different protocols of 300, 600, and 900 V, respectively, while delivering twenty 100 µs bursts of a 150 kHz biphasic square wave to five tissues; cardiac muscle, skeletal muscle, liver, carotid artery and sciatic nerve. Lesions were evaluated quantitatively by histologic analysis and by morphometric evaluation. There were eight, seven and eight animals in the 300, 600, and 900 V protocols, respectively. High-frequency electroporation protocols showed a graded effect on myocardial tissue with larger lesions in the 900 V protocol compared with the other two protocols as demonstrated by width (P = 0.02), length (P = 0.01) and fibrosis ratio (P = 0.001). This effect was not observed for other tissues with attenuated degree of damage. No damage to the carotid artery was observed in all protocols. Partial damage to the sciatic nerve was observed in only two samples (25%) in the 600 V group and in one sample (14.3%) in the 900 V group. CONCLUSION: Electroporation effect is tissue-specific such that myocardium is more prone to electroporation damage compared with neural and vascular tissues. Our results suggest no neural or vascular damage with using a low-amplitude HF-IRE protocol. Further investigation is warranted to better identify other tissue-specific thresholds.

CHA2DS2-VASC Score Predicts the Risk of Stroke in Patients Hospitalized to the Internal Medicine Department Without Known Atrial Fibrillation.

BACKGROUND: The CHA2DS2-VASC score is used to assess the risk of cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) or atrial flutter (AFL). OBJECTIVES: We aimed to determine whether this score can determine the risk of CVA during the first year after hospitalization, in patients without known AF/AFL. DESIGN: Single-center retrospective cohort. PATIENTS: We included all patients aged ≥ 50 who were hospitalized between January 1, 2008, and December 31, 2018, to the internal medicine departments at the Chaim Sheba Medical Center, Israel. Exclusion criteria included history or new diagnosis of CVA, TIA, and AF/AFL and use of anticoagulation at any time. MAIN MEASURES: Patients were stratified into 3 groups according to their CHA2DS2-VASC score (0-1, 2, or ≥ 3). The primary outcome was hospitalization with CVA/TIA within one year of the index hospitalization. KEY RESULTS: Of the patients, 52,206 were included in the study. CVA/TIA occurred in 0.7%, 1.3%, and 1.7% of patients with a CHA2DS2-VASC score of 0-1, 2, and ≥ 3, respectively. Compared to a CHA2DS2-VASC score of 0-1, the HR for CVA/TIA occurrence for CHA2DS2-VASC scores of 2 and ≥ 3 was 1.77 (CI 1.42, 2.22) and 2.33 (CI 1.9, 2.85), respectively (p < 0.001 for both comparisons). Each additional CHA2DS2-VASC point increased the probability for readmission with CVA/TIA within 1-year by 26% (HR 1.26, CI 1.19, 1.32, p < 0.001). Similar trends were seen in subgroup analyses by gender, age, and renal function. CONCLUSIONS: The CHA2DS2-VASC score is a predictor for CVA/TIA during the first year after hospitalization in patients without AF. High CHA2DS2-VASC scores warrant work-up for occult AF/AFL and other risk factors for CVA/TIA.

Procedural and long-term outcome among patients undergoing expedited trans-catheter aortic valve replacement.

OBJECTIVE: Patients with rapidly deteriorating clinical status due to severe aortic stenosis are often referred for expedited transcatheter aortic valve replacement (TAVR). Data regarding the outcome of such interventions is limited. We aimed to evaluate the outcome of patients undergoing expedited TAVR. DESIGN AND SETTING: Data were derived from the Israeli Multicenter Registry. SUBJECTS: Subjects were divided into two groups based on procedure urgency: patients who were electively hospitalized for the procedure (N = 3140) and those who had an expedited TAVR (N = 142). Procedural and periprocedural complication rates were significantly higher among patients with an expedited indication for TAVR compared to those having an elective procedure: valve malposition 4.6% versus 0.6% (p < 0.001), procedural cardiopulmonary resuscitation 4.3% versus 1.0% (p = 0.007), postprocedure myocardial infarction 2.0% versus 0.4% (p = 0.002), and stage 3 acute kidney injury 3.0% versus 1.1%, (p < 0.001). Patients with expedited indication for TAVR had significantly higher in hospital mortality (5.6% vs. 1.4%, p = 0.003). Kaplan-Meier's survival analysis showed that patients undergoing expedited TAVR had higher 3-year mortality rates compared to patients undergoing an elective TAVR procedure (p < 0.001). Multivariate analysis found that patients with expedited indication had fourfolds increased risk of in-hospital mortality (odds ratio: 4.07, p = 0.001), and nearly twofolds increased risk of mortality at 3-year (hazard ratio: 1.69, p = 0.001) compared to those having an elective procedure. CONCLUSION: Patients with expedited indications for TAVR suffer from poor short- and long-term outcomes. It is important to characterize and identify these patients before the deterioration to perform TAVR in a fast-track pathway to minimize their procedural risk.

Cardiac ablation with pulsed electric fields: principles and biophysics.

Pulsed electric fields (PEFs) have emerged as an ideal cardiac ablation modality. At present numerous clinical trials in humans are exploring PEF as an ablation strategy for both atrial and ventricular arrhythmias, with early data showing significant promise. As this is a relatively new technology there is limited understanding of its principles and biophysics. Importantly, PEF biophysics and principles are starkly different to current energy modalities (radiofrequency and cryoballoon). Given the relatively novel nature of PEFs, this review aims to provide an understanding of the principles and biophysics of PEF ablation. The goal is to enhance academic research and ultimately enable optimization of ablation parameters to maximize procedure success and minimize risk.

Echocardiographic Ventricular Septal Motion Abnormalities Are Associated With Pre-Capillary Pulmonary Hypertension in Patients With Preserved Left Ventricular Function.

BACKGROUND: Ventricular septal motion abnormalities (VSMA) are common echocardiographic finding in patients with pulmonary hypertension (PHTN). This study sought to evaluate the relationship between echocardiographic findings and the classification of PHTN. METHODS: This study retrospectively studied 146 consecutive patients referred for right heart catheterisation for clinically suspected PHTN. VSMA were defined as any echocardiographic description of leftward abnormal septal motion or position. RESULTS: VSMA were present in 42 patients (29%). Patients with VSMA were younger and more likely to have prior pulmonary embolism. They also had less obstructive sleep apnoea, hypertension and dyslipidaemia. By echocardiography, patients with VSMA had lower left ventricular mass, left atrial size and lateral wall E/e' ratio. At cardiac catheterisation, PHTN was confirmed in all (100%) patients with VSMA (compared with 75% in patients without VSMA); 98% with VSMA had elevated pulmonary vascular resistance (compared with 55% without VSMA; p<0.005 for all). VSMA were found to have 91% sensitivity and 51% specificity for the diagnosis of pre-capillary PHTN. On multivariate analysis, VSMA were found to be strong independent predictors for the diagnosis of pre-capillary PHTN (HR, 9.15; 95% CI, 3.0-28.2; p<0.001). Left atrial enlargement was also a strong negative predictor for pre-capillary PHTN (HR, 0.14; 95% CI, 0.05-0.36; p<0.001). CONCLUSION: Ventricular septal motion abnormalities were strongly associated with pre-capillary PHTN in patients with suspected PHTN. The findings suggest that patients with VSMA should be further evaluated by right heart catheterisation.

Comparison of permanent pacemaker implantation rate after first and second generation of transcatheter aortic valve implantation-A retrospective cohort study.

OBJECTIVES: This study aimed to compare permanent pacemaker implantation (PPMI) rates among patients undergoing Trans-catheter Aortic Valve Implantation (TAVI) with first generation (G1) versus second generation (G2) valves and the impact of PPMI on long-term mortality. BACKGROUND: PPMI is a known adverse event after TAVI. Recently, two novel iterations of valve designs of both the balloon expandable valves (BEV) and self-expanding valves (SEV) were introduced as a second generation valves. METHODS: All patients included in the Israeli multicenter TAVI registry were grouped according to valve type (BEV vs. SEV) and generation (G1 vs. G2). A comparison was made for clinical and outcome indices of patients undergoing TAVI with G1 and G2 in each of the valve systems. RESULTS: A total of 1377 patients were included. The incidence of PPMI did not differ between G1-BEV versus G2-BEV (15.3% vs. 17.4%; p = 0.598) nor between G1-SEV versus G2-SEV (23.4% vs. 20.3%; p = 0.302). Depth of implantation and complete right bundle branch block were independently associated with PPMI post-TAVI in both valve systems. PPMI was not associated with an increased risk for 2-year mortality. CONCLUSIONS: The incidence of PPMI remains a relevant adverse event post-TAVI even when the newer generation valves are used. Since the predictors for PPMI are well established, a standardized approach for the management of conduction disorders is much needed.

Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports.

AIM: There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID-19) pandemic. We analysed real-world data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ-associated cardiovascular adverse events (CVAEs) in pre-COVID-19 reports. METHODS: We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014-9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 ). RESULTS: The full database contained 6 677 225 reports with a mean (±SD) age of 53 (±17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3-35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3-6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8-2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9-2.7], all IC025 > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ-associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively). CONCLUSION: In a real-world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ-associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off-label indication, especially for patients with cardiac disorders.

High fitness might be associated with the development of new-onset atrial fibrillation in obese non-athletic adults.

BACKGROUND: Data on the association between AF and fitness are conflicting. OBJECTIVES: The aim of this analysis was to investigate the association between fitness, obesity and incidence of atrial fibrillation (AF) among apparently healthy non-athlete adults. METHODS: We investigated 20 410 self-referred subjects who were annually screened in a tertiary medical centre. All subjects were free of AF and completed maximal exercise stress test according to the Bruce protocol at baseline. Fitness was categorised into age- and sex-specific quintiles (Q) according to the treadmill time. Subjects were categorised to low (Q1-Q2) and high fitness (Q3-5) groups. The primary end point was new-onset AF during follow-up. RESULTS: Mean age was 48 ± 10 years and 72% were men. A total of 463 (2.3%) events occurred during an average follow-up of 8 ± 5 years corresponding to an AF event rate of 0.3% per person year. Univariate and multivariate models showed that AF risk was similar in both fitness groups. However, AF event rate was 0.55% per person year among high fitness obese subjects, compared with 0.31% for low fitness obese subjects (P < .01). Subgroup interaction analysis showed that AF risk is obesity-dependent, such that in the obese group (≥30 kg/m2 ) high fitness was independently associated with a significant 79% increased AF risk (95% CI 1.15-2.78; P = .01), whereas among non-obese subjects the rate of events was similar between both fitness groups (P for interaction = (.02)). CONCLUSIONS: Our findings suggest that high fitness might be associated with increased AF risk among obese subjects.

Sex Disparities in First Medical Contact of Patients with Suspected Acute Coronary Syndrome Using Telemedicine Technology.

Background:Reducing door-to-balloon time may not reduce mortality, but reducing the time from symptom onset to first medical contact (FMC) may alone improve patient outcomes. The purpose of this study was to focus on analyzing sex differences in FMC call delay and its trend over the decades in patients with suspected acute coronary syndrome (ACS).Methods:Large private telemedicine data in patients with suspected ACS were used to investigate time delay in contacting a telemedicine call center. We identified 24,592 calls to a primary call center of patients with anginal symptoms and first electrocardiogram (ECG), using mobile 12-lead ECG devices. For the purpose of the current analysis, we included the first call of 14,420 patients for whom demographic, clinical ECG data were available.Results:First mobile ECG changes included suspected S-T Segment (ST) elevation in 2,220 (16%) cases, ST depression in 3,143 (22%) cases, or both in 685 (5%) patients. There were 6,721 (47%) calls to the center within less than 1 h of symptom onset. Chest pain, dyspnea, heart rate, male sex, absence of diabetes mellitus, early time period of the study, and ischemic ST segment changes on the first ECG were all independently associated with the increased likelihood of contacting the center within less than 1 h of symptom onset to FMC (p < 0.01 for all).Conclusions:Both chest pain and ischemic ECG changes were sex dependent for early medical contact, as such factors were significant among men (p = 0.001 and p = 0.024, respectively), but not among women (p = 0.024). The later time period of the study was associated with a shorter time delay among women more than that of men (p = 0.014). Women with prehospital chest pain or ischemic ST segment changes tend to seek medical help later than men. Temporal trends show attenuation of this sex disparity, with more women presenting earlier in the last decade.

The association between fasting plasma glucose and glycated hemoglobin in the prediabetes range and future development of hypertension.

BACKGROUND: Prediabetes is a well-established risk factor for progression to overt diabetes mellitus (DM), which is in turn associated with development of hypertension (HTN) and vice versa. However, the role of prediabetes and HbA1c in particular as an independent risk factor for the development of hypertension is unclear. AIM: In this current study, we aimed to evaluate the association between both fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels in the prediabetes range and development of HTN among a large cohort of normotensive subjects. DESIGN AND METHODS: We investigated 5016 normotensive participants without DM and other cardiovascular risk factors who were annually screened in a tertiary medical center. Subjects were divided into normoglycemic and prediabetic groups. Normoglycemia was defined as HbA1c < 5.7% and FPG < 100 mg/dl. Prediabetes was defined according to the ADA criteria, i.e., 6.5% > HbA1c ≥ 5.7% or impaired fasting glucose (IFG):126 mg/dl > FPG ≥ 100 mg/dl. Subgroup analysis was made by dividing participants into four groups according to FPG and HbA1C levels, i.e., normoglycemia, impaired HbA1c only, IFG only, and both parameters impaired. RESULTS: During a follow-up of 3.7 ± 2.9 years, 318 (6.3%) subjects developed HTN. A cumulative hazard function for the development of hypertension showed a 2.89-fold ([95% CI 2.19-3.83], p < .0001) increased risk for HTN in the prediabetic population. In a multivariable Cox proportional hazard regression model adjusted to common confounding risk factors for HTN, prediabetes was found to be independently associated with a 1.95-fold ([95%, CI 1.43-2.52] p < .0001) increased risk for hypertension. Impaired HbA1C only was not found to be independently associated with HTN, while IFG only showed a 2.13-fold (95%, [CI 1.46-3.11] p < .0001) increased risk for HTN compared to normoglycemic, and a 2.55-fold ([95% CI 1.85-3.51] p < .0001) increased risk for HTN when both parameters impaired. CONCLUSION: Our study demonstrates that FPG in the prediabetes range, albeit not glycated hemoglobin, is independently and significantly associated with future development of HTN. Therefore, our findings further highlight the pivotal predictive role of IFG for HTN development as opposed to the limited independent role of abnormal HbA1c levels.

Metformin therapy in patients with diabetes mellitus is associated with a reduced risk of vasculopathy and cardiovascular mortality after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Reduced cardiovascular mortality and morbidity have been reported in non-HT patients treated with metformin. Given the high prevalence of type 2 diabetes mellitus (T2DM) in HT patients, we investigated the association between metformin therapy and cardiovascular outcomes after HT. METHODS: The study population comprised 103 DM patients who had undergone HT between 1994 and 2018 and were prospectively followed-up. We excluded from the study patients with type 1 diabetes mellitus. Fifty-five HT patients (53%) in the cohort were treated with metformin. Clinical data were recorded on prospectively designed forms. The primary outcomes included CAV, survival, and the combined end-point of CAV or cardiovascular mortality. RESULTS: Kaplan-Meier survival analysis showed that the CAV rate at 20 years of follow-up was lower in DM patients treated with metformin than in those who were not (30 vs. 65%; log-rank p = 0.044). Similarly, the combined risk of CAV or cardiovascular mortality was lower in the metformin-treated patients than in those not receiving metformin (32 vs. 68%; log rank p = 0.01). Consistently, multivariate analysis adjusted for age and comorbidities showed that metformin therapy was independently associated with a significant 90% reduction (95% confidence interval 0.02-0.46, p = 0.003) in the risk for the development of CAV, and a 91% reduction (95% confidence interval 0.02-0.42; p = 0.003) in the risk for CAV or cardiovascular mortality. CONCLUSIONS: In diabetic HT patients, metformin therapy is independently associated with a significant reduction in the long-term risk for CAV and the combined end-point of CAV or cardiovascular mortality after HT.

Effect of percutaneous paravalvular leak closure on hemolysis.

OBJECTIVE: To study the effect of percutaneous paravalvular leak closure on hemolysis. BACKGROUND: Although transcatheter PVL closure reduces heart failure and mortality in symptomatic patients with paravalvular leaks (PVL), little is known about its effect on hemolysis. METHODS: We retrospectively analyzed patients undergoing transcatheter mitral or aortic PVL closure (January 2005-December 2016) at Mayo Clinic. Patients with anemia or abnormal hemolysis markers (LDH, haptoglobin) were included in the analysis. The primary outcome was defined as hemoglobin increase ≥ 1.5 mg/dL, decrease in LDH above median or improvement in haptoglobin. Univariate and multivariate binary logistic regression modeling were used to determine predictors of successful treatment of hemolysis. RESULTS: Final study population included 168 patients (130 [77%] mitral, 38 [23%] aortic PVL). Primary outcome occurred in 70 patients (42%). Hemoglobin increased by 1.74 ± 1.69 mg/dL in patients who reached primary outcome. 57/168 (34%) patients required blood transfusion prior to PVL closure compared to 35/168 (21%) postprocedure. The mean reduction in LDH was 403 U/L. Multivariate regression showed that patients with mechanical valves were more likely to have successful outcome (P = 0.044). CONCLUSION: Percutaneous PVL closure is associated with modest improvement in hemolysis markers, increase in hemoglobin levels and reduction in blood transfusion requirements. This benefit is most significant in patients with mechanical valves.

A hybrid technique for treatment of commissural primary mitral regurgitation.

BACKGROUND: MitraClip is an effective transcatheter therapy for mitral regurgitation (MR). However, MitraClip is challenging in commissural MR and the optimal therapeutic approach is unclear. METHODS: We describe a case series of six consecutive patients with severe commissural primary mitral regurgitation who underwent MitraClip insertion followed by an Amplatzer Vascular Plug (AVP) II occluder between the commissure and the MitraClip. RESULTS: The procedure was successful in all patients. MR was reduced from severe to mild/trivial in 50% and moderate in 50% of cases. On 30-day follow-up, NYHA class had improved from III (6 patients) to I (2 patients), II (2 patients), and III (2 patients). The mean transmitral gradient was 2.5 ± 1.8 mmHg at baseline and 4.8 ± 2.6 mmHg following the procedure. One patient developed hemolysis immediately post procedure. The other five patients remained well during a median follow-up of 20 months (range 5-50 months) with no reported device dislodgement. CONCLUSIONS: Elective treatment of severe commissural MR with a laterally or medially placed MitraClip coupled with an AVP II occluder between the clip and the commissure is feasible and safe. This approach may provide a useful management alternative in selected patients.

Procedural trends, outcomes, and readmission rates pre-and post-FDA approval for MitraClip from the National Readmission Database (2013-14).

BACKGROUND: There are sparse clinical data on the procedural trends, outcomes and readmission rates following FDA approval and expansion of Transcatheter mitral valve repair/MitraClip® . Whether a complex new technology can be disseminated safely and quickly is controversial. METHODS: The study cohort was derived from the National Readmission Data (NRD) 2013-14. MitraClip® was identified using appropriate International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. The primary outcome was a composite of in-hospital mortality + procedural complications. Secondary outcome included 30-day readmissions. Hierarchical two level logistic models were used to evaluate study outcomes. RESULTS: Our analysis included 2003 MitraClip® procedures. Overall in-hospital mortality was 3.9%. As expected, there was a significant increase in procedural volume post-FDA approval. Importantly, a corresponding downward trend in mortality and procedural complications was observed. Significant predictors of in-hospital mortality and procedural complications included the use of vasopressors (P <0.001) and hemodynamic support (P < 0.001). Higher hospital volume (≥10 MitraClips/year) was associated with lower in-hospital mortality and complications (P = 0.02). There were 304 (15.1%) 30-day readmissions, with heart failure being the most common cause of readmission. Elective procedures had lower in-hospital mortality (P < 0.001) and lower readmission rates (P = 0.011) compared with nonelective procedures. CONCLUSION: A significant increase in MitraClip® procedural volumes occurred post-FDA approval. Overall morbidity and mortality were low and trended downwards. Hospital procedure volume ≥10 cases were associated with lower mortality and overall complication rates. These data suggest a successful roll out of a very complex novel structural heart procedure.

Early Referral to Coronary Artery Bypass Grafting Following Acute Coronary Syndrome, Trends and Outcomes from the Acute Coronary Syndrome Israeli Survey (ACSIS) 2000-2010.

BACKGROUND: Limited information exists on whether changes in medical practices over the study decades have affected the outcomes of acute coronary syndrome (ACS) patients who undergo early coronary artery bypass surgery (CABG) during index hospitalisation. METHODS: Data on trends for early CABG referral and associated outcomes were obtained among 11,485 ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010. RESULTS: Among 11,485 patients, 566 (5%) were referred to early CABG. These patients displayed higher risk characteristics, including Killip class >II, anterior myocardial infarction, greater left ventricular dysfunction, and more frequent use of mechanical ventilation and intra-aortic balloon pump (all p<0.01). Nevertheless, mortality rates of patients referred to early CABG vs. treated with percutaneous coronary intervention (PCI) or medically, was similar (11.4% vs. 10.2%; log-rank p-value=0.40). There was a significant decline in the referral trend over the study decade (6.7% - 1.7%; p<0.001). One year survival was similar between patients referred to early CABG during the late (years: 2006-2010) vs. early (years: 2000-2005) period (85.7% vs. 90%; log-rank p-value=0.15), whereas, among patients who didn't undergo early CABG, and underwent percutaneous coronary intervention (PCI) or medical management only, enrolment during the late periods was associated with a significant survival benefit (91.5% vs. 88.1%; log-rank p-value<0.001). CONCLUSIONS: Over the study decade there was a significant decline in referral for early CABG, without a difference in the one-year mortality between the early and non-early CABG group.