Dimensionless index and outcome in patients with aortic valve disease.

PURPOSE: Assessment of aortic stenosis (AS) is based on aortic valve (AV) gradients and calculation of aortic valve area (AVA). These parameters are influenced by flow and dependent on geometric assumptions. The dimensionless index (DI), the ratio of the LVOT time-velocity integral to that of the AV jet, is simple to perform, and is less susceptible to error but has only been examined in small selected groups of AS patients. The objective of this study was to assess the DI and prognosis in a large cohort. METHODS: All subjects who underwent echocardiography with an assessment of the AV that included DI were included. Association between AV parameters including mean gradient, AVA, DI and AV resistance and mortality and cardiovascular hospitalizations was examined. RESULTS: A total of 9393 patients (mean age 71 ± 16 years; 53% male) were included. 731 (7.7%) patients had DI less than .25. Increasing age and a diagnosis of heart failure were significantly associated with lower DI. Subjects with low DI had significantly lower ventricular function, a higher incidence of mitral and tricuspid regurgitation, worse diastolic function and more elevated pulmonary pressures. Decreasing DI was associated with significantly decreased survival and event-free survival which remained highly significant on multivariate analysis. CONCLUSIONS: In a large population of patients with AV disease, decreased DI, was associated with increased mortality and decreased event-free survival. The easily obtained DI identifies a broad range of AS subjects with worse prognosis and should be integrated into the assessment of these complex patients.

Pre- and Post-transcatheter Aortic Valve Replacement (TAVR) Serum Mean Platelet Volume Levels and All-Cause Mortality.

BACKGROUND: Among the most frequent complications following transcatheter aortic valve replacement (TAVR) is hemostasis imbalance that presents either as thromboembolic or bleeding. Deviations in platelet count (PC) and mean platelet volume (MPV) are markers of hemostasis imbalance. OBJECTIVES: To determine the predictive value of pre- and post-procedural PC and MPV fL 1-year all-cause mortality in patients who underwent TAVR. METHODS: In this population-based study, we included 236 TAVR patients treated at the Tzafon Medical Center between 1 June 2015 and 31 August 2018. Routine blood samples for serum PC levels and MPV fL were taken just before the TAVR and 24-hour post-TAVR. We used backward regression models to evaluate the predictive value of PC and MPV in all-cause mortality in TAVR patients. RESULTS: In this study cohort, MPV levels 24-hour post-TAVR that were greater than the cohort median of 9 fL (interquartile range 8.5-9.8) were the strongest predictor of 1-year mortality (hazard ratio 1.343, 95% confidence interval 1.059-1.703, P-value 0.015). A statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables. CONCLUSIONS: Serum MPV levels fL 24-hour post-procedure were found to be meaningful markers in predicting 1-year all-cause mortality in patients after TAVR.

Mass to voltage ratio index predicts mortality following TAVI.

Transcatheter aortic valve implantation (TAVI) is commonly performed in elderly patients with aortic stenosis. Better methods of risk stratification are needed in this population with high morbidity. There is a relatively high incidence of cardiac amyloidosis in this population and high LV mass index (LVMI) to QRS voltage may help identify patients with worse prognosis following TAVI. This retrospective study enrolled consecutive patients who underwent TAVI in our institution between the years 2008-2019. Mass voltage ratio index (MVRi) was calculated as the ratio of LV mass index on echocardiogram to voltage using the Sokolow-Lyon criteria on 12 lead ECG performed within 3 months before the intervention. Two hundred and fifty-one patients (mean age 80.8 years, 49% men) were enrolled. One hundred and sixty-eight (67%) patients were alive at 3 years follow up. MVRi was a statistically significant predictor of 3 year mortality (p < 0.005). Patients were divided categorically into tertiles based on MVRi score; the "high" group had significantly higher 3-year mortality (p < 0.001). In the multivariate model only Euroscore (p < 0.009) and MVRi (p < 0.011; OR: 2.32; CI: 1.15-4.964) were statistically significant predictors of mortality. The "high" group had a significantly lower survival rate after 3 years follow up on Kaplan-Meier analysis (p < 0.001). Our findings suggest that MVRi is a strong, independent predictor of increased post-TAVI mortality. This may be a simple clinical tool to assist in the assessment of patients prior to before TAVI.

Ticagrelor versus Prasugrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Analysis from the Acute Coronary Syndrome Israeli Survey.

INTRODUCTION: We aimed to compare the outcomes of acute coronary syndrome (ACS) patients undergoing in-hospital percutaneous coronary intervention treated with prasugrel versus ticagrelor. METHODS: Among 7,233 patients enrolled to the Acute Coronary Syndrome Israeli Survey (ACSIS) between 2010 and 2018, we identified 1,126 eligible patients treated with prasugrel and 817 with ticagrelor. Comparison between the groups was performed separately in ST-elevation myocardial infarction (STEMI) patients, propensity score matched (PSM) STEMI patients, and non-ST-elevation ACS (NSTE-ACS) patients. RESULTS: In-hospital complication rates, including rates of stent thrombosis, were not significantly different between groups. In PSM STEMI patients, 30-day re-hospitalization rate (p < 0.05), 30-day MACE (the composite of death, MI, stroke, and urgent revascularization, p = 0.006), and 1-year mortality rates (p = 0.08) were higher in the ticagrelor group compared to the prasugrel group; in NSTE-ACS patients, outcomes were not associated with drug choice. In Cox regression analysis applied on the entire cohort, prasugrel was associated with lower 1-year mortality in STEMI patients but not in NSTE-ACS patients (p for interaction 0.03). CONCLUSIONS: Compared to ticagrelor, prasugrel was associated with superior clinical outcomes in STEMI patients, but not in NSTE-ACS patients.

Assessing the Performance of a Novel Point-of-Care Qualitative Assay for Early Diagnosis of Acute Coronary Syndrome.

BACKGROUND: Early and accurate diagnosis of acute coronary syndrome (ACS) is essential for initiating lifesaving interventions. In this article, the diagnostic performance of a novel point-of-care rapid assay (SensAheart©) is analyzed. This assay qualitatively determines the presence of 2 cardiac biomarkers troponin I and heart-type fatty acid-binding protein that are present soon after onset of myocardial injury. METHODS: We conducted a prospective observational study of consecutive patients who presented to the emergency department with typical chest pain. Simultaneous high-sensitive cardiac troponin T (hs-cTnT) and SensAheart testing was performed upon hospital admission. Diagnostic accuracy was computed using SensAheart or hs-cTnT levels versus the final diagnosis defined as positive/negative. RESULTS: Of 225 patients analyzed, a final diagnosis of ACS was established in 138 patients, 87 individuals diagnosed with nonischemic chest pain. In the overall population, as compared to hs-cTnT, the sensitivity of the initial SensAheart assay was significantly higher (80.4 vs. 63.8%, p = 0.002) whereas specificity was lower (78.6 vs. 95.4%, p = 0.036). The overall diagnostic accuracy of SensAheart assay was similar to the hs-cTnT (82.7% compared to 76.0%, p = 0.08). CONCLUSIONS: Upon first medical contact, the novel point-of-care rapid SensAheart assay shows a diagnostic performance similar to hs-cTnT. The combination of 2 cardiac biomarkers in the same kit allows for very early detection of myocardial damage. The SensAheart assay is a reliable and practical tool for ruling-in the diagnosis of ACS.

Electrocardiographic Predictors of Long-Term Cardiac Pacing Dependency Following Transcatheter Aortic Valve Implantation.

BACKGROUND: Conduction disorders requiring permanent pacemaker (PPM) implantation are a known complication of transcatheter aortic valve implantation (TAVI). Indications for permanent pacing in this setting are still controversial. The study aim was to characterize the natural history of conduction disorders related to TAVI, and to identify predictors for long-term pacing dependency. METHODS: Consecutive patients who underwent TAVI were included in this prospective observational study. The conduction system was investigated by reviewing 12-lead ECGs during hospitalization and up to 1-year follow-up and by analyzing pacemaker interrogation data. Multivariate analysis was performed in order to identify independent predictors for pacemaker dependency. RESULTS: Of 110 patients included in the analysis, 38 (34.5%) underwent PPM implantation. Of those, 26 (68.4%) had a long-term pacing dependency (required PPM), while 12 (31.6%) did not (not-required PPM). Logistic regression revealed that baseline RBBB (P = 0.01, OR = 18.0), baseline PR interval (P = 0.019, OR = 1.14), post-TAVI PR interval and the change in PR interval from baseline (P < 0.001 for both, OR = 1.17 for each 10 milliseconds increment) were independent predictors for long-term pacing dependency. A PR interval increment of greater than 28 milliseconds had the best accuracy in predicting pacemaker dependency. CONCLUSIONS: Increased pre- and postprocedural PR intervals and pre-existing RBBB are reliable predictors for long-term PPM dependency, while left bundle branch block or QRS width are misleading factors. Our study suggests that the decision for implanting PPM after TAVI should be based mostly on the prolongation of the PR interval.

Real-World Use of Novel P2Y12 Inhibitors in Patients with Acute Myocardial Infarction: A Treatment Paradox.

OBJECTIVE: To assess the real-world use, clinical outcomes, and adherence to novel P2Y12 inhibitors. METHODS: We evaluated 1,093 consecutive acute myocardial infarction patients undergoing a percutaneous intervention. Patients were derived from a prospective, multicenter, nationwide registry and were followed for 30 days; 381 patients (35%) received clopidogrel, 468 (43%) received prasugrel, and 244 (22%) received ticagrelor. Patients treated with clopidogrel were older and more likely to suffer from chronic renal failure and stroke and/or present with non-ST-elevation myocardial infarction (NSTEMI) (p < 0.01 for all). Independent predictors of undertreatment with novel P2Y12 inhibitors included: older age (OR 0.17; 95% CI 0.1-0.27, p < 0.0001), a prior stroke (OR 0.41; 95% CI 0.2-0.68, p = 0.008), and NSTEMI (OR 0.37; 95% CI 0.26-0.54, p < 0.0001). RESULTS: Novel P2Y12 inhibitors were associated with a lower incidence of cardiovascular events, major bleeding, and/or death (7.6 vs.11%, HR 0.67; 95% CI 0.43-1, p = 0.05). However, after a multivariate analysis this trend was not statistically significant. Patients discharged with ticagrelor versus thienopyridines demonstrated a higher rate of crossover to other P2Y12 inhibitors (11 vs. 5%, p = 0.03). CONCLUSIONS: In a real-world cohort, there was an underutilization of novel P2Y12 inhibitors which was more pronounced in higher-risk subsets that might benefit from novel P2Y12 inhibitors at least as much as other patients.

Sex difference and outcome trends following surgical aortic valve replacement from the National Inpatient Sample (NIS) Database.

BACKGROUND: Based on worldwide registries, approximately 50% of patients who underwent aortic valve replacement (AVR) via surgical aortic valve replacement are females. Although AVR procedures have improved greatly in recent years, differences in outcome including mortality between sexes remain. We aimed to investigate the trends in SAVR outcomes in females versus males. METHODS: Using the 2011-2017 National Inpatient Sample (NIS) database, we identified hospitalizations for patients with diagnosis of aortic stenosis during which SAVR was performed. Patients' sociodemographic and clinical characteristics, procedure complications, and mortality were analyzed. Piecewise regression analyses were performed to assess temporal trends in SAVR utilization in females versus males. Multivariable analyses were performed to identify predictors of in-hospital mortality. RESULTS: A total of 392,087 hospitalizations for SAVR across the USA were analyzed. Utilization of SAVR in both sex patients decreased significantly during the years 2011-2017. Males compared to females had significantly higher rates of hyperlipidemia, chronic renal disease, peripheral artery disease, coronary artery disease and tended to be smokers. Differences in mortality rates among sexes were observed for SAVR procedures. Women had higher in-hospital mortality with 3.7% compared to men with 2.5% (OR 1.38 [95% CI 1.33-1.43, P<0.001]). In a multivariable regression model analysis adjusted for potential confounders, women had higher mortality risk with odd ratio (OR 1.38 [95% CI 1.33-1.43], P<0.001). Women had significantly higher rates of vascular complications (5.1% compared to men with 4.6%, P=0.002). CONCLUSIONS: Utilization of SAVR showed a downward trend during the study period. Higher in-hospital mortality was recorded in females compared to males.

The impact of aging on cardiac remodeling in chronic mitral regurgitation.

BACKGROUND: Chronic mitral regurgitation (MR) is a volume overload state that causes dilatation of the left sided cardiac chambers. The presence of significant dilatation is considered an indication for mitral valve intervention, however, aging may affect left ventricular (LV) remodeling independently of valvular disease. The objective of this study was to examine age-related changes in cardiac remodeling in a broad population of patients with chronic MR. METHODS: Consecutive subjects that underwent echocardiography examinations recorded in the echocardiography database of a university-affiliated laboratory were retrieved. Subjects were categorized into none/mild, moderate or severe MR. For purposes of analysis of differences with aging, the population was divided into groups above and below 70 years of age and standard echocardiographic measurements were compared between the groups. RESULTS: A total of 3492 subjects with at least moderate MR (mean age: 76 years, 52% female) were included in the study and compared to 18,250 subjects with none or mild MR. Older patients had significantly smaller LV end-diastolic diameters and volumes and significantly larger left atrial (LA) volumes when compared to the younger group. LA volume index increased in both age groups as MR severity increased, while LV end-diastolic volume increased with increasing MR only in the younger population. CONCLUSIONS: Cardiac remodeling in chronic MR is significantly influenced by age. Guideline based recommendations of timing of mitral valve interventions in asymptomatic MR patients, based on assessment of LA and LV remodeling, may need to take age into account.

Effect of pharmacological heart failure drugs and gene therapy on Danon's cardiomyopathy.

Danon disease is a rare X-linked genetic disease resulting from LAMP2 mutations leading to defective lysosomal function. Heart failure is the main causes of morbidity and mortality. Mice with an LAMP2-exon-6-deletion (L2Δ6), develop cardiac hypertrophy followed by dilated cardiomyopathy, in association with accumulation of autophagosomes, fibrosis and oxidative stress. We investigated the effect of drugs used to treat heart failure and of LAMP2 gene therapy on the phenotype, molecular markers and ROS in LAMP2 cardiomyopathy. L2Δ6 mice were treated with Angiotensin II, Ramipril, Metoprolol or Spironolactone. Gene therapy was delivered by IP injection of Adeno-associated-virus (AAV9) -LAMP2 vector to neonates ("AAVLAMP2-Prevention"), or at 15 weeks of age ("AAVLAMP2-Treatment"). Angiotensin II markedly aggravated the cardiac phenotype. Ramipril and Spironolactone were effective in attenuating left ventricular hypertrophy and preserving the systolic function. Cardiac protection was associated with decreased autophagosome accumulation, reduced fibrosis and oxidative stress. Gene therapy effectively attenuated autophagosome accumulation and ROS in L2Δ6 hearts, lowering troponin release to nearly normal levels. AAVLAMP2-Prevention protected against systolic dysfunction and decreased hypertrophy. AAVLAMP2-Treatment prevented ventricular dilatation and dysfunction but had no effect on wall thickness. We conclude that RAAS inhibitors are highly effective against cardiomyopathy progression in an experimental mouse model of Danon's and shall be considered in human patients for this purpose until novel therapies become clinically available.

Outcomes of Acute Coronary Syndrome Patients Who Presented with Cardiogenic Shock versus Patients Who Developed Cardiogenic Shock during Hospitalization.

Background: Cardiogenic shock (CS) continues to be a severe and fatal complication of acute coronary syndrome (ACS). CS patients have a high mortality rate despite significant progress in primary reperfusion, the management of heart failure and the expansion of mechanical circulatory support strategies. The present study addressed the clinical characteristics, management, and outcomes of ACS patients complicated with CS. Methods: We performed an observational study, using the 2000-2013 Acute Coronary Syndrome Israeli Surveys (ACSIS) database and identified hospitalizations of ACS patients complicated with CS. Patients' demographics and clinical characteristics, complications and outcomes were evaluated. We assessed the outcomes of ACS patients with CS at arrival (on the day of admission) compared with ACS patients who arrived without CS and developed CS during hospitalization. Results: The cohort included 13,434 patients with ACS diagnoses during the study period. Of these, 4.2% were complicated with CS; 224 patients were admitted with both ACS and CS; while 341 ACS patients developed CS only during the hospitalization period. The latter patients had significantly higher rates of MACEs compared with the group of ACS patients who presented with CS at arrival (73% vs. 51%; p < 0.0001). Similarly, the rates of in-hospital mortality (55% vs. 36%; p < 0.0001), 30-day mortality (64% vs. 50%; p = 0.0013) and 1-year mortality (73% vs. 59%; p = 0.0016) were higher in ACS patients who developed CS during hospitalization vs. ACS patients with CS at admission. There was a significant decrease in 1-year mortality trends during the 13 years of this study presented in ACS patients from both groups. Conclusions: Patients who developed CS during hospitalization had higher mortality and MACE rates compared with those who presented with CS at arrival. Further studies should focus on this subgroup of high-risk patients.

Outcomes of patients with acute coronary syndrome according to COVID-19 vaccination status.

BACKGROUND: COVID-19 vaccination has been associated with reduced risk of acute coronary syndrome (ACS); however, several studies have reported cardiovascular complications following vaccination. We aimed to investigate the effect of COVID-19 vaccination status on the treatment and outcome of ACS patients. METHODS: The study was based on the 2021 Acute Coronary Syndrome Israeli Survey. Patients were stratified into two groups according to COVID-19 vaccination status, vaccinated compared to unvaccinated. Patients who had received at least 2 vaccination doses up to 1 week prior to ACS hospitalization were considered vaccinated. The primary endpoint was 1-year all-cause mortality. RESULTS: A total of 1261 patients with ACS were included, of whom 990 (78.5%) were vaccinated. Vaccinated patients were older and less frequently smokers. There were no significant differences in coronary reperfusion rates and treatment with guideline-based medical therapy during hospital stay and at discharge. The primary endpoint of 1-year all-cause mortality occurred in 38 (3.8%) and 14 (5.2%) patients in the vaccinated and unvaccinated groups respectively (P = 0.42). 30-day MACE occurred in 94 (9.5%) in the vaccinated patients compared to 31 (11.5%) in the unvaccinated group (P = 0.39). These results remained similar following adjustment for confounders. CONCLUSION: There was no association between COVID-19 vaccination status and the outcomes of patients with ACS. Our findings provide support for the cardiovascular safety of COVID-19 mRNA vaccines in patients at high cardiovascular risk.

The Relationship Between Body Mass Index and In-hospital Survival in Patients Admitted With Acute Heart Failure.

Background: The association between Body Mass Index (BMI) and clinical outcomes following acute heart failure (AHF) hospitalization is debated in the literature. Our objective was to study the real-world relationship between BMI and in-hospital mortality in patients who were admitted with AHF. Methods: In this retrospective, multi-center study, we utilized the National Inpatient Sample (NIS) database to identify a sampled cohort of patients who were hospitalized with AHF between October 2015 and December 2016. Outcomes of interest included in-hospital mortality and length of stay (LOS). Patients were divided into 6 BMI (kg/m2) subgroups according to the World Health Organization (WHO) classification: (1) underweight ≤ 19, (2) normal weight 20-25, (3) overweight 26-30, (4) obese I 31-35, (5) obese II 36-39, and (6) extremely obese ≥40. A multivariable logistic regression model was used to identify predictors of in-hospital mortality and to identify predictors of LOS. Results: A weighted total of 219,950 hospitalizations for AHF across the US were analyzed. The mean age was 66.3 ± 31.5 years and most patients (51.8%) were male. The crude data showed a non-linear complex relationship between BMI and AHF population outcomes. Patients with elevated BMI exhibited significantly lower in-hospital mortality compared to the underweight and normal weight study participants (5.5, 5,5, 2,8, 1.6, 1.4, 1.6% in groups by BMI ≤ 19, 20-25, 26-30, 31-35, 36-39, and, ≥40 respectively, p < 0.001) and shorter LOS. In the multivariable regression model, BMI subgroups of ≤ 25kg/m2 were found to be independent predictors of in-hospital mortality. Age and several comorbidities, and also the Deyo Comorbidity Index, were found to be independent predictors of increased mortality in the study population. Conclusion: A reverse J-shaped relationship between BMI and mortality was documented in patients hospitalized for AHF in the recent years confirming the "obesity paradox" in the real-world setting.

Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial‡.

AIMS: Current guidelines recommend anticoagulation with a vitamin K antagonist to treat left ventricular (LV) thrombus after myocardial infarction (MI). Data on the use of direct oral anticoagulants (DOACs) in this setting are limited. The aim of the study was to assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. METHODS AND RESULTS: We conducted a prospective, randomized, multicentre open-label clinical trial including patients with LV thrombus detected by 2D transthoracic echocardiography 1-14 days after acute MI. Thirty-five patients were enrolled in three medical centres; 17 patients were randomized to warfarin and 18 patients to apixaban. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Secondary outcomes were major bleeding, stroke or systemic embolism, re-hospitalization, and all-cause mortality. Mean LV thrombus size at enrolment was 18.5 mm × 12.3 mm in the warfarin group and 19.9 mm × 12.4 mm in the apixaban group (P = NS). Thirty-two patients completed 3 months follow-up. In the warfarin group, two patients withdrew, and in the apixaban group one patient died. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 patients in the apixaban group (P = NS and P = 0.026 for non-inferiority). Two patients had major bleeding in the warfarin group, while no major bleeding events were recorded in the apixaban group. There was one stroke in the warfarin group and one death in the apixaban group. CONCLUSION: Our results suggest that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI with a 20% non-inferiority margin.

Autophagy guided interventions to modify the cardiac phenotype of Danon disease.

Danon disease is a lethal X-linked genetic syndrome resulting from radical mutations in the LAMP2 gene. LAMP2 protein deficiency results in defective lysosomal function, autophagy arrest and a multisystem disorder primarily involving the heart, skeletal muscle and the central nervous system. Cardiomyopathy is the main cause of morbidity and mortality. To investigate the mechanisms of and develop therapies for cardiac Danon disease we engineered a mouse model carrying an exon 6 deletion human mutation in LAMP2, which recapitulates the human cardiac disease phenotype. Mice develop cardiac hypertrophy followed by left ventricular dilatation and systolic dysfunction, in association with progressive fibrosis, oxidative stress, accumulation of autophagosomes and activation of proteasome. Stimulation of autophagy in Danon mice (by exercise training, caloric restriction, and rapamycin) aggravate the disease phenotype, promoting dilated cardiomyopathy. Inhibiting autophagy (by high fat diet or hydroxychloroquine) is better tolerated by Danon mice compared to wild type but is not curative. Inhibiting proteasome by Velcade was found to be highly toxic to Danon mice, suggesting that proteasome is activated to compensate for defective autophagy. In conclusion, activation of autophagy should be avoided in Danon patients. Since Danon's is a lifelong disease, we suggest that lifestyle interventions to decrease cardiac stress may be useful to slow progression of Danon's cardiomyopathy. While Danon mice better tolerate high fat diet and sedentary lifestyle, the benefit regarding cardiomyopathy in humans needs to be balanced against other health consequences of such interventions.

Impact of the Admission Pathway on the Gender-Related Mortality of Patients With ST-Elevation Myocardial Infarction.

The mortality of women with ST-elevation myocardial infarction (STEMI) exceeds that of men, supposedly the result of older age and co-morbidities. Patients with STEMI can be transported directly to the catherization lab by the emergency medical service (EMS) or to the emergency department (ED) by the EMS, a regular ambulance, or independently. This raises the question whether gender disparity in the transport of patients with STEMI may affect time to therapy and consequently explain the disparate outcome in men and women with STEMI. We analyzed a large nationwide registry of prospectively-recorded patients with acute coronary syndromes in order to determine if there is a survival gap between men and women with STEMI, and to assess the gender-related effect of admission pathway on time intervals and 5-year mortality. Study population included 2,740 patients with STEMI who underwent primary percutaneous coronary interventions, comprising 464 women (17%, median-70 years) and 2,276 men (83%, median-58 years). The unadjusted 5-year mortality of women was higher compared with men (26.4% vs 15.6%, p = 0.001) but adjustment abrogated this survival difference. Regardless of adjustment, the 5-year mortality of patients with STEMI admitted directly to the catherization lab or to the ED by EMS was similar for men and women but significantly lower in the directly admitted patients (p <0.028). In contrast, admission to the ED by non-EMS was associated with markedly worse survival among women. These results indicate that women suspected of STEMI benefit from transportation by the EMS and should use this pathway exclusively to reach the hospital.

Coenzyme Q10 in the Treatment of Heart Failure with Preserved Ejection Fraction: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).

Prevention of ventricular arrhythmia and calcium dysregulation in a catecholaminergic polymorphic ventricular tachycardia mouse model carrying calsequestrin-2 mutation.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload and increased Ca(2+) leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. METHOD AND RESULTS: CPVT mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, ß-adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca(2+) content in mutant myocytes, diminished diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented Ca(2+) oscillations in stressed mutant myocytes. CONCLUSIONS: Ca(2+) channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT.

Long-Term Prognosis in Young Patients with Acute Coronary Syndrome Treated with Percutaneous Coronary Intervention.

BACKGROUND: Acute coronary syndrome (ACS) at a young age is uncommon. Limited data regarding the long-term follow-up and prognosis in this population are available. Our objectives were to evaluate the long-term clinical outcomes of patients presenting with ACS at a young age and to assess factors that predict long-term prognosis. METHODS: A retrospective analysis of consecutive young patients (male below 40 and female below 50 years old) that were admitted with ACS and underwent percutaneous coronary intervention (PCI) between the years 1997 and 2009. Demographics, clinical characteristics, and clinical outcomes including major cardiovascular (CV) events and mortality were analyzed. Multivariable cox proportional hazard model was performed to identify predictors of long-term prognosis. RESULTS: One-hundred sixty-five patients were included with a mean follow-up of 9.1±4.6 years. Most patients were men (88%), and mean age (years) was 36.8±4.2. During follow-up, 15 (9.1%) died, 98 (59.4%) patients had at least one major CV event, 22 (13.3%) patients had more than two CV events, and the mean number of recurrent CV events was 1.4±1.48 events per patient. In multivariate analysis, the strongest predictors of major CV events and/or mortality were coronary intervention without stent insertion (HR1.77; 95% CI 1.09-2.9), LAD artery involvement (HR 1.59; 95% CI 1.04-2.44) and hypertension (HR 1.6; 95% CI 1.0-2.6). CONCLUSION: Patients with ACS in young age are at high risk for major CV and/or mortality in long-term follow-up with a high rate of recurrent CV events. Close follow-up and risk factor management for secondary prevention have a major role, particularly in this population.

The impact of short hospital stay on prognosis after acute myocardial infarction: An analysis from the ACSIS database.

BACKGROUND: Current evidence regarding the optimal length of hospital stay (LOS) following myocardial infarction (MI) is limited. This study aimed to examine LOS policy for MI patients and to assess the safety of early discharge. METHODS: A prospective observational study that included patients with STEMI and NSTEMI enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) during the years 2000-2016. Patients were divided into three subgroups according to their LOS: <3 days (short-LOS), 3-6 days (intermediate-LOS) and >6 days (long-LOS). We compared baseline characteristics, management strategies and clinical outcomes at 30 days and 1 year in these groups. RESULTS: Ten thousand four hundred and fifty eight patients were enrolled in the study. The LOS of MI patients gradually decreased over time. Short-LOS and intermediate-LOS patients had similar clinical characteristics while patients in the long-LOS group were older with more co-morbidity. There was no difference in the clinical outcomes, including re-MI, arrhythmias, 30 days MACE, and 30 days mortality between the short-LOS and intermediate-LOS groups. However, the rate of re-hospitalizations was higher in the short-LOS group (20.9% vs. 17.8%, p = .004) without evidence of increased cardiovascular events. In multivariate analysis, the LOS did not predict either 30 days mortality (HR: 1.3; CI:0.45-5.48), nor MACE at 30 days (HR: 1.1; CI:0.79-1.56). CONCLUSION: Our study suggests that an early discharge strategy of up to 3 days from admission is safe for low and intermediate-risk patients after both STEMI and NSTEMI. Nevertheless, this strategy is associated with an increased risk of potential avoidable readmission and there might be psychological and social factors that may warrant a longer stay.