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.

Hyperphosphatemia is required for initiation but not propagation of kidney failure-induced calcific aortic valve disease.

High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uremia-inducing diet, with or without phosphate enrichment, to rats for 7 wk. Forty-two rats were fed with a phosphate-enriched uremic regimen that caused renal insufficiency and hyperphosphatemia. Another 42 rats were fed with a phosphate-depleted uremic regimen, which induces similar severity of renal insufficiency, but without its related mineral disorder. Aortic valves were evaluated at several points during the time of diet administration. In the second part, additional 54 rats were fed a phosphate-enriched diet for various time periods and were then switched to a phosphate-depleted diet to complete 7 wk of uremic diet. Osteoblast-like phenotype, inflammation, and eventually valve calcification were observed only in rats that were fed with a phosphate-enriched regimen. Significant valve calcification was observed only in rats that were fed a phosphate-enriched diet for at least 4 wk. Valve calcification was observed only when the switch to a phosphate-depleted regimen occurred after osteoblast markers and activation of Akt and ERK intracellular signaling pathways had already been found in the valve. Phosphate is essential for the initiation of the calcification process. However, when osteoblast markers are already expressed in valve tissue, phosphate depletion will not halt the disease.NEW & NOTEWORTHY High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease. However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. Our findings indicated that phosphate is essential for the initiation of the process that includes macrophage accumulation and osteoblast phenotype. Furthermore, hyperphosphatemia is dispensable beyond a certain phase of the process, a point of "no return" after which phosphate depletion does not prevent calcification. This point is relatively early in the course of calcification, when no calcification is apparent, but the inflammation, osteoblast markers, and activation of ERK and Akt pathways have already been identified. Our findings emphasize the complexity of the calcification process and suggest that different mediators might be required during different phases and that the role of phosphate precedes the actual calcification.

For Whom the Bell Tolls : Refining Risk Assessment for Sudden Cardiac Death.

Sudden cardiac death is one of the most important causes of death worldwide. Advancements in medical treatment, percutaneous interventions, and device therapy (ICD and CRTD) showed consistent reduction in mortality, mainly in survivors of SCD and in patients with ischemic cardiomyopathy and depressed left ventricular function. Patients with non-ischemic cardiomyopathies, mildly reduced LV function, and channelopathies have increased risk for SCD. Identifying the subgroup of these patients before they experience life-threatening or fatal events is essential to further improve outcomes. In this review, we aimed to summarize the current knowledge for risk stratification and primary prevention, to describe the gaps in evidence, and to discuss future directions for screening and treating patients at risk for SCD. PURPOSE OF REVIEW: The purpose of this review is to provide a comprehensive description of the etiologies of sudden cardiac death, risk stratification strategies, and to describe the current medical and interventional therapies. We aimed to discuss the current gaps in our knowledge of primary prevention of SCD and to review novel approaches and interventions. RECENT FINDINGS: The incidence of SCD has decreased in the last two decades due to improved pharmacological treatment and ICD implantation in SCD survivors and in patients with reduced left ventricular function and ischemic cardiomyopathy. The efficacy of ICD in patients with non-ischemic cardiomyopathy is challenged by new findings from the DANISH trial. Catheter ablation is new emerging strategy to prevent SCD in patients with scar relater or PVC-triggered ventricular arrhythmias. Despite the new treatments, SCD is still a major burden. ICD remains the cornerstone for patients with ischemic cardiomyopathy, whereas appropriate risk stratification of the patients with non-ischemic cardiomyopathy and channelopathies is needed to further improve outcomes. The future of ablation as the treatment and prevention of SCD remains to be studied.

Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle.

BACKGROUND: Acute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome. METHODS AND RESULTS: Patients admitted to a tertiary hospital with a clinical diagnosis of acute myocarditis were evaluated; 193 patients were included. Median follow-up was 5.7 years, 82% were male, and overal median age was 30 years (range 21-39). The most common clinical presentations were chest pain (77%) and fever (53%). The 30-day survival rate was 98.9%. Overall survival during follow-up was 94.3%. The most common abnormalities observed on electrocardiography were T-wave changes (36%) and ST-segment changes (32%). Less frequent changes included abnormal T-wave axis (>105° or < -15°; 16%), abnormal QRS axis (12%), QTc >460 ms (11%), and QRS interval ≥120 ms (5%). Wide QRS-T angle (≥100°) was demonstrated in 13% of the patients and was associated with an increased mortality rate compared with patients with a narrow QRS-T angle (20% vs 4%; P = .007). The rate of heart failure among patients with a wide QRS-T angle was significantly higher (36% vs 10%; P = .001). Cox regression analysis demonstrated that a wide QRS-T angle (≥100°) was a significant independent predictor of heart failure (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.35-7.59; P < .01) and of the combined end point of death or heart failure (HR 2.56, 95% CI 1.14-5.75; P < .05). CONCLUSIONS: QRS-T angle is a predictor of increased morbidity and mortality in acute myocarditis.

Unrecognised cardiovascular disease in type 2 diabetes: is it time to act earlier?

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be 'silent' or 'asymptomatic', but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.

Degenerative mitral regurgitation predicts worse outcomes in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: To evaluate the role mitral regurgitation (MR) etiology and severity play in outcomes for patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Multiple prior studies have investigated the influence of MR severity on outcomes for patients undergoing TAVR. Less has been published regarding the effects of MR etiology on outcomes, including its impact on heart failure hospitalization. METHODS: Two hundred and seventy patients undergoing TAVR at 2 hospitals were enrolled. Each patient had a baseline and follow-up (within 30 days of TAVR) echocardiogram that was analyzed. MR was graded as none, mild, moderate, or severe, as well as functional or degenerative. We compared patient outcomes, including death and heart failure hospitalization, among none-mild MR, moderate-severe functional MR, and moderate-severe degenerative MR groups. RESULTS: Two hundred and seventy patients underwent TAVR, reducing mean aortic valve gradients from 45 ± 15 mm Hg to 9 ± 4 mm Hg. On multivariable analysis, only patients with moderate-severe degenerative MR had decreased survival free of death or CHF hospitalization compared to those with none-mild MR (P = .011). Subanalysis showed patients with moderate-severe degenerative MR were more likely to be hospitalized for heart failure at 2 years compared to those with moderate-severe functional MR (P = .02). Patients with moderate-severe degenerative MR were also less likely to have improvement in MR severity at follow up (P = .01). CONCLUSIONS: Special consideration should be given to patients with moderate-severe degenerative MR undergoing TAVR. As transcatheter approaches for mitral valve repair and replacement continue to evolve, moderate-severe degenerative MR patients may benefit from consideration of double valve intervention.

[LONG TERM FOLLOW-UP OF TRANSCATHETER SELF EXPANDABLE AORTIC VALVE IMPLANTATION].

INTRODUCTION: Aortic stenosis is the most common significant valvular disease in the western world. These patients are treated operatively unless they are at high operative risk or inoperable. During the last decade an alternative approach has evolved - transcatheter aortic valve implantation (TAVI). This method was shown to be at least as effective and safe as the operative one. However, very little data exists on long term follow-up (5 years and above), especially regarding valve durability and patient survival. OBJECTIVES: To present a long term follow-up on patients who underwent transcutaneous self-expandable aortic valve implantation in our department between the years 2008-2011. METHODS: In September 2008 the first CoreValve implantation was performed in Israel at Hadassah Medical Center. All records of patients who were transplanted between 9.2008 and 10.2011 were reviewed. The function of the valve early after the procedure was compared to its function at the end of the follow-up period. RESULTS: A total of 38 patients (out of 71) survived at least 54 months, of them, 19 have an echocardiography examination at the end of the follow-up period. In all patients the implanted valve was found to function well at the end of the follow-up period, without significant stenosis or paravalvular leak. In fact, in approximately half of these patients, the degree of paravalvular leak decreased during the follow-up period. DISCUSSION: On long term (5 years) follow-up of patients who were implanted with the self-expandable aortic valve (CoreValve), no deterioration of the valve was observed. In fact, in approximately half of the patients, a decrease in the severity of the paravalvular leak was demonstrated.

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.

The Glider registry.

BACKGROUND: Provisional stenting of the side-branch (SB) is the universally accepted gold standard while there is still controversy on the usefulness of routine dilatation of the SB ostium. Recrossing the struts of a previously deployed stent with a wire and a balloon can prove challenging and is occasionally unsuccessful, mainly because the balloon tip hits a stent strut. This prospective multicenter international registry tested the crossing ability procedural results of a new-dedicated ultrashort balloon specifically designed for side branch dilatation (Glider, TriReme Medical, Pleasanton, CA, USA). METHODS: One hundred and twenty five patients (for a total of 131 bifurcation lesions) were enrolled in the registry between January 2009 and May 2012. The Glider was used as first choice in alternative to conventional balloon (group I, 72%) or as bail-out after unsuccessful previous attempt at crossing with small conventional low-profile balloons (group II, 28%). Postprocedural coronary artery dissections and in-hospital MACE (death, myocardial infarction and repeat revascularization) were assessed. Technical success was defined as the ability of the Glider to recross the struts of a previously deployed stent while procedural success was defined as less of residual 50% diameter stenosis at the origin of the SB with a final TIMI 3 and/or freedom from in-hospital MACE. RESULTS: Technical success was achieved, respectively, in 92% (group I), and 83% (group II). Clinical and angiographic procedural success was achieved in 98% of the lesions. In Group II, no other balloon of the same size could cross in cases where Glider could not. A total of 13 complications were observed, including nine ostial SB dissection four of which needed a second stent on the SB, one stent loss, two severe coronary spasms, and two by thrombus formation. CONCLUSION: The unique possibility offered by this short dedicated balloon to orientate its beveled tip provides an effective strategy for recrossing stent struts when conventional low profile balloons fail achieving greater SB ostial expansion thus reducing the incidence of strut malapposition during provisional treatment of bifurcational lesions. © 2016 Wiley Periodicals, Inc.

Pericardial covered stent for coronary perforations.

OBJECTIVES: To evaluate initial and long term results of coronary perforation treatment with pericardial covered stent. BACKGROUND: Iatrogenic coronary perforation is a rare life threatening complication of percutaneous coronary interventions (PCI) occurring in 0.1-0.8% of cases. Covered stents are the mainstay of therapy for coronary perforation. However, polytetrafluoroethylene covered stents are bulky with limited flexibility and thus may not be easy to deliver in difficult anatomy. Therefore, they are reserved to perforations in proximal or mid straight segments where their delivery is relatively easy. The pericardial covered stent is a highly deliverable fully covered stent that may be used to treat coronary perforations. Only a single case has been reported of the use of this stent in its previous version for the treatment of coronary perforation. METHODS: The electronic databases of four tertiary medical centers were retrospectively reviewed for cases of coronary perforations in which PCS was used. During a five years period, between 2008 and 2013, 18,364 patients underwent PCI in these centers. Nine cases of perforations for which balloon dilatation was not sufficient and pericardial covered stent was used were recorded. RESULTS: All nine cases were successfully treated with pericardial covered stent. Six of the patients underwent repeated angiography at 2-15 months, and in two of them instent restenosis that warranted repeated angioplasty was observed. One of them was catheterized for NSTEMI 3 months after the covered stent implantation, and stent thrombosis was demonstrated. CONCLUSIONS: Pericardial covered stents offer a safe and effective therapy for coronary perforation when balloon inflation and reversal of anticoagulation are insufficient.

Oxygen therapy in acute coronary syndrome: are the benefits worth the risk?

Oxygen supplementation is a standard treatment for all patients who present with acute coronary syndrome, regardless of oxygen saturation levels. Most of the data regarding the function of oxygen in myocardial infarction is based on a limited number of basic and clinical studies. We performed a systematic literature review that explores the basic and clinical data on the function of oxygen in ischaemic heart disease and myocardial infarction. This review discusses many aspects of oxygen treatment: (i) basic studies on the effects of oxygen in ischaemia and the potential cardiovascular effects of oxygen metabolites; (ii) clinical trials that have assessed the value of inhaled oxygen, supersaturated oxygen, and intracoronary injection of hyperoxaemic solutions in myocardial infarction; and (iii) the haemodynamic effects of oxygen in various clinical scenarios and its direct effects on the coronary vasculature. Our findings suggest that there are conflicting data on the effects of oxygen treatment. Further, the potential harmful effects of oxygen must be considered, particularly in myocardial infarction. These findings question the current guidelines and recommendations and emphasize the need for large clinical trials.

Short-term therapy with R568 ameliorated secondary hyperparathyroidism but does not prevent aortic valve calcification in uremic rats.

Introduction: Renal failure associated aortic valve calcification (AVC) is the result of hyperphosphatemia and hyperparathyroidism. Calcimimetics is an effective tool for management of secondary hyperparathyroidism. Our goal was to evaluate the effect of the medical intervention with calcimimetic R568 on the AVC process. Methods and results: The experimental design consisted of administering a uremia-inducing phosphate-enriched diet to rats for six weeks. Rats received a daily R568 injection at different times. Biochemical analysis demonstrated increased urea (34.72 ± 3.57 vs. 5.18 ± 0.15 mmol/L, p<0.05) and creatinine (293.93 ± 79.6 vs. 12.82 ± 1.56 µmol/L, p<0.05). R568 treatment markedly reduced parathyroid hormone (PTH) levels in both treated groups (192.63 ± 26.85, 301.23 ± 101.79 vs. 3570 ± 986.63 pg/mL, p<0.05), with no impact on serum calcium and phosphate. von Kossa staining showed increase in AVC in uremic rats compared to control (1409 ± 159.5 vs. 27.33 ± 25.83, p<0.05). AVC was not affected by R568 in both groups (3343 ± 2462, 1593 ± 792 vs. 1409 ± 159.5, NS). Similarly, the inflammatory marker CD68 was elevated in uremic rats (15592 ± 3792 vs. 181.8 ± 15.29, p<0.01), and was not influenced by R568 treatment (8453 ± 818.5, 9318 ± 2232 vs. 15592 ± 3792, NS). Runt-related transcription factor 2 (Runx2), the regulator of osteoblast differentiation, was upregulated in uremic rats (23186 ± 9226 vs. 3184 ± 2495), that accompanied by elevated levels of Osteopontin (158395 ± 45911 vs. 237.7 ± 81.5, p<0.05) and Osteocalcin (22203 ± 8525 vs. 489.7 ± 200.6, p<0.05). R568 had no impact on osteoblastic markers (Runx2: 21743 ± 3193, 23004 ± 10871 vs. 23186 ± 9226, NS; osteopontin: 57680 ± 19522, 137116 ± 60103 vs. 158395 ± 45911, NS; osteocalcin: 10496 ± 5429, 8522 ± 5031 vs. 22203 ± 8525, NS). Conclusion: In an adenine-induced uremic rat model, we showed that short-term R568 therapy had no effect on AVC. Treatment with R568 decreased PTH levels but had no effect on high phosphate levels. Regression of AVC necessitates not only a decrease in PTH levels, but also a decline in phosphate levels. To achieve improved outcomes, it is advisable to consider administering a combination of R568 with other medications, such as calcium supplements or phosphate binders. Additional studies are required for further evaluation of the potential treatment of chronic kidney disease (CKD)-associated AVC.

The incidence and prognosis of renal dysfunction following cardioversion of atrial fibrillation.

OBJECTIVE: Limited data are available regarding the incidence and clinical impact of renal dysfunction following cardioversion of atrial fibrillation. The objective of this study was to assess the incidence and implications of renal dysfunction following cardioversion of atrial fibrillation. METHODS: We conducted a nested case-control study to determine the incidence, timing, risk factors and outcome of atrial fibrillation cardioversion associated with renal dysfunction (AFCARD) in a tertiary medical center. Consecutive patients undergoing direct current cardioversion (DCCV) for atrial fibrillation in our institution during 2008-2009 with measurements of creatinine before and following cardioversion were included. AFCARD was defined as a rise in serum creatinine greater than 25% from baseline within a week following DCCV. RESULTS: One hundred and twelve patients were included in the study, of whom 19 (17%) developed AFCARD. One patient required hemodialysis. Patients with AFCARD had a higher incidence of advanced heart failure, diabetes mellitus and were more frequently treated with digoxin and enoxaparin. Patients with AFCARD had a significantly decreased survival rate at 1 year (63 vs. 92%; p < 0.001). CONCLUSIONS: AFCARD is relatively common and is associated with increased mortality. These findings suggest a role for close surveillance of renal function following DCCV.

Pacing system malfunction is a rare cause of hospital admission for syncope in patients with a permanent pacemaker.

BACKGROUND: Few studies have examined the prevalence of permanent pacemaker (PPM) malfunction among patients with a previously implanted pacemaker admitted to the hospital with syncope. OBJECTIVE: This study sought to examine causes of syncope in patients with a previously implanted pacemaker admitted to our hospital with syncope. METHODS: We retrospectively reviewed our hospital admission database for patients who had both keywords "syncope" and "pacemaker" as their diagnoses from January 1, 1995 until June 1, 2012. One hundred and sixty-two patients who were admitted to the hospital because of syncope and had a PPM implanted prior to the index syncopal episode were included. All patients had pacemakers interrogated during the admission. Two independent physicians examined the discharge summary of each patient and determined the cause of syncope in each case. RESULTS: Of the 162 patients studied, eight (4.9%) were found to have pacemaker system malfunction as a cause of syncope. In 96 patients (59.2%), the cause of syncope could not be determined prior to hospital discharge. Among the identifiable causes of syncope, orthostatic hypotension was most prevalent (16%) followed by vasovagal (6%), severe aortic stenosis (4.3%), atrial arrhythmia (3.1%), acute and subacute infection (3.1%), and other less prevalent causes (3.1%). CONCLUSION: In this study, PPM system malfunction was rarely a cause of syncope in patients admitted to the hospital with a previously implanted device.

Correlations between the alpha-Gal antigen, antibody response and calcification of cardiac valve bioprostheses: experimental evidence obtained using an alpha-Gal knockout mouse animal model.

Introduction: Preformed antibodies against αGal in the human and the presence of αGal antigens on the tissue constituting the commercial bioprosthetic heart valves (BHVs, mainly bovine or porcine pericardium), lead to opsonization of the implanted BHV, leading to deterioration and calcification. Murine subcutaneous implantation of BHVs leaflets has been widely used for testing the efficacy of anti-calcification treatments. Unfortunately, commercial BHVs leaflets implanted into a murine model will not be able to elicit an αGal immune response because such antigen is expressed in the recipient and therefore immunologically tolerated. Methods: This study evaluates the calcium deposition on commercial BHV using a new humanized murine αGal knockout (KO) animal model. Furtherly, the anti-calcification efficacy of a polyphenol-based treatment was deeply investigated. By using CRISPR/Cas9 approach an αGal KO mouse was created and adopted for the evaluation of the calcific propensity of original and polyphenols treated BHV by subcutaneous implantation. The calcium quantification was carried out by plasma analysis; the immune response evaluation was performed by histology and immunological assays. Anti-αGal antibodies level in KO mice increases at least double after 2 months of implantation of original commercial BHV compared to WT mice, conversely, the polyphenols-based treatment seems to effectively mask the antigen to the KO mice's immune system. Results: Commercial leaflets explanted after 1 month from KO mice showed a four-time increased calcium deposition than what was observed on that explanted from WT. Polyphenol treatment prevents calcium deposition by over 99% in both KO and WT animals. The implantation of commercial BHV leaflets significantly stimulates the KO mouse immune system resulting in massive production of anti-Gal antibodies and the exacerbation of the αGal-related calcific effect if compared with the WT mouse. Discussion: The polyphenol-based treatment applied in this investigation showed an unexpected ability to inhibit the recognition of BHV xenoantigens by circulating antibodies almost completely preventing calcific depositions compared to the untreated counterpart.

Abbreviated or Standard Antiplatelet Therapy in HBR Patients: Final 15-Month Results of the MASTER-DAPT Trial.

BACKGROUND: Clinical outcomes and treatment selection after completing the randomized phase of modern trials, investigating antiplatelet therapy (APT) after percutaneous coronary intervention (PCI), are unknown. OBJECTIVES: The authors sought to investigate cumulative 15-month and 12-to-15-month outcomes after PCI during routine care in the MASTER DAPT trial. METHODS: The MASTER DAPT trial randomized 4,579 high bleeding risk patients to abbreviated (n = 2,295) or standard (n = 2,284) APT regimens. Coprimary outcomes were net adverse clinical outcomes (NACE) (all-cause death, myocardial infarction, stroke, and BARC 3 or 5 bleeding); major adverse cardiac and cerebral events (MACCE) (all-cause death, myocardial infarction, and stroke); and BARC type 2, 3, or 5 bleeding. RESULTS: At 15 months, prior allocation to a standard APT regimen was associated with greater use of intensified APT; NACE and MACCE did not differ between abbreviated vs standard APT (HR: 0.92 [95% CI: 0.76-1.12]; P = 0.399 and HR: 0.94 [95% CI: 0.76-1.17]; P = 0.579; respectively), as during the routine care period (HR: 0.81 [95% CI: 0.50-1.30]; P = 0.387 and HR: 0.74 [95% CI: 0.43-1.26]; P = 0.268; respectively). BARC 2, 3, or 5 was lower with abbreviated APT at 15 months (HR: 0.68 [95% CI: 0.56-0.83]; P = 0.0001) and did not differ during the routine care period. The treatment effects during routine care were consistent with those observed within 12 months after PCI. CONCLUSIONS: At 15 months, NACE and MACCE did not differ in the 2 study groups, whereas the risk of major or clinically relevant nonmajor bleeding remained lower with abbreviated compared with standard APT. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Changes in uric acid levels and allopurinol use in chronic heart failure: association with improved survival.

OBJECTIVE: Uric acid (UA) levels are frequently increased in patients with heart failure (HF), and may be an indicator of a poor prognosis and an innovative target for treatment. We evaluated the effect of UA and allopurinol use on clinical outcome in patients with HF. METHODS AND RESULTS: We evaluated patients with a diagnosis of HF at a Health Maintenance Organization (n = 6204). Patients were followed for cardiac-related hospitalizations and death. Mean UA levels were 6.5 ± 1.9 mg/dL. Median follow-up was 498 days. We divided patients into quartiles of serum UA; 22.6% (n = 1,568) were in the highest UA level quartile (>7.7 mg/dL). Cox regression analysis after adjustment for significant predictors including age, sex, ischemic heart disease, hypertension, atrial fibrillation, body mass index, hemoglobin, sodium, estimated glomerular filtration rate, urea levels, standard HF drug therapies, and allopurinol demonstrated that high UA levels (>7.7 mg/dL) were a predictor of increased mortality (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.17-1.60; P < .0001) and increased cardiac hospitalizations (HR 1.10, 95% CI 1.01-1.22; P < .05). An increase in UA levels during follow-up was also an independent predictor of mortality (HR 1.46, 95% CI 1.25-1.71; P < .00001) and cardiac hospitalizations (HR 1.15, 95% CI 1.06-1.23; P < .00001). Treatment with allopurinol was independently associated with improved survival (HR 0.79, 95% CI 0.64-0.98; P < .05). Echocardiographic data demonstrated a significant correlation between UA levels and E/A ratio, a marker of diastolic dysfunction. CONCLUSIONS: Increased UA levels and an increase in UA during follow-up were independent predictors of increased morbidity and mortality. Treatment with allopurinol was associated with improved survival.

Remote Speech Analysis in the Evaluation of Hospitalized Patients With Acute Decompensated Heart Failure.

OBJECTIVES: This study assessed the performance of an automated speech analysis technology in detecting pulmonary fluid overload in patients with acute decompensated heart failure (ADHF). BACKGROUND: Pulmonary edema is the main cause of heart failure (HF)-related hospitalizations and a key predictor of poor postdischarge prognosis. Frequent monitoring is often recommended, but signs of decompensation are often missed. Voice and sound analysis technologies have been shown to successfully identify clinical conditions that affect vocal cord vibration mechanics. METHODS: Adult patients with ADHF (n = 40) recorded 5 sentences, in 1 of 3 languages, using HearO, a proprietary speech processing and analysis application, upon admission (wet) to and discharge (dry) from the hospital. Recordings were analyzed for 5 distinct speech measures (SMs), each a distinct time, frequency resolution, and linear versus perceptual (ear) model; mean change from baseline SMs was calculated. RESULTS: In total, 1,484 recordings were analyzed. Discharge recordings were successfully tagged as distinctly different from baseline (wet) in 94% of cases, with distinct differences shown for all 5 SMs in 87.5% of cases. The largest change from baseline was documented for SM2 (218%). Unsupervised, blinded clustering of untagged admission and discharge recordings of 9 patients was further demonstrated for all 5 SMs. CONCLUSIONS: Automated speech analysis technology can identify voice alterations reflective of HF status. This platform is expected to provide a valuable contribution to in-person and remote follow-up of patients with HF, by alerting to imminent deterioration, thereby reducing hospitalization rates. (Clinical Evaluation of Cordio App in Adult Patients With CHF; NCT03266029).

The RAISE Trial: A Novel Device and First-in-Man Trial.

BACKGROUND: Currently, standard medical therapies have limited effects on heart failure with preserved ejection fraction (HFpEF), which impacts on the life quality and survival of patients. This study aimed to evaluate the safety and efficacy of the percutaneous radiofrequency ablation-based interatrial shunting for HFpEF with a novel atrial septostomy device. METHODS: A preclinical study in 11 normal domestic pigs and the first-in-man study in 10 patients with HFpEF were performed. The major safety events and interatrial shunt performance were evaluated at baseline, 1 month, 3 months, and 6 months post-procedure in both animals and human patients. The clinical functional status was also assessed in the first-in-man study. RESULTS: Percutaneous radiofrequency ablation-based interatrial shunting therapy was performed successfully both in animals and patients. In the animal study, a left-to-right interatrial shunt was created with a mean defect size of 5.5±2.2 mm without procedure-related safety events. Seven pigs showed the continuous shunting with a mean defect size of 4.1±1.5 mm at 6 months. In the first-in-man study, a median interatrial defect diameter of 5.0 (4.0-6.0) mm was measured immediately. No major safety events including death and thromboembolism were observed. The continuous shunting with the defect size of 4.0 (3.0-4.0) mm could still be observed in 7 patients at 6 months. The clinical status was significantly improved with NT-proBNP (N-terminal pro-B-type natriuretic peptide) reduced by 2149 pg/mL ([95% CI, 204-3301] P=0.028), with 6-minute walk distance increased by 88 m ([95% CI, 50-249] P=0.008) and with New York Heart Association class improved in 8 patients at 6 months. CONCLUSIONS: The present results showed that percutaneous radiofrequency ablation-based interatrial shunting was a safe and potentially effective therapy for HFpEF, providing a nonpharmacological and nonimplanted option for HFpEF management. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900027664.