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).

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.

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).

Feasibility of remote speech analysis in evaluation of dynamic fluid overload in heart failure patients undergoing haemodialysis treatment.

AIMS: This study aimed to assess the ability of a voice analysis application to discriminate between wet and dry states in chronic heart failure (CHF) patients undergoing regular scheduled haemodialysis treatment due to volume overload as a result of their chronic renal failure. METHODS AND RESULTS: In this single-centre, observational study, five patients with CHF, peripheral oedema of ≥2, and pulmonary congestion-related dyspnoea, undergoing haemodialysis three times per week, recorded five sentences into a standard smartphone/tablet before and after haemodialysis. Recordings were provided that same noon/early evening and the next morning and evening. Patient weight was measured at the hospital before and after each haemodialysis session. Recordings were analysed by a smartphone application (app) algorithm, to compare speech measures (SMs) of utterances collected over time. On average, patients provided recordings throughout 25.8 ± 3.9 dialysis treatment cycles, resulting in a total of 472 recordings. Weight changes of 1.95 ± 0.64 kg were documented during cycles. Median baseline SM prior to dialysis was 0.87 ± 0.17, and rose to 1.07 ± 0.15 following the end of the dialysis session, at noon (P = 0.0355), and remained at a similar level until the following morning (P = 0.007). By the evening of the day following dialysis, SMs returned to baseline levels (0.88 ± 0.19). Changes in patient weight immediately after dialysis positively correlated with SM changes, with the strongest correlation measured the evening of the dialysis day [slope: -0.40 ± 0.15 (95% confidence interval: -0.71 to -0.10), P = 0.0096]. CONCLUSIONS: The fluid-controlled haemodialysis model demonstrated the ability of the app algorithm to identify cyclic changes in SMs, which reflected bodily fluid levels. The voice analysis platform bears considerable potential as a harbinger of impending fluid overload in a range of clinical scenarios, which will enhance monitoring and triage efforts, ultimately optimizing remote CHF management.

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.

Albuminuria: Associated With Heart Failure Severity and Impaired Clinical Outcomes.

BACKGROUND: Urinary albumin to creatinine ratio (UACR) is common in patients with heart failure (HF) and may have an impact on clinical outcome. We evaluated the effect of UACR on clinical outcome in a real-world cohort of patients with HF. METHODS: All patients with HF at a health maintenance organization were followed for cardiac-related hospitalizations and death. RESULTS: The study cohort included 4668 patients with HF and was divided into 3 groups based on UACR: normal-range albuminuria (2085 patients; 45%), microalbuminuria (1769 patients; 38%), and macroalbuminuria (814 patients; 17%). Microalbuminuria and macroalbuminuria were both associated with increasing age, diabetes mellitus, hypertension, peripheral vascular disease, atrial fibrillation, and New York Heart Association class III/IV. Microalbuminuria and macroalbuminuria were directly associated with decreased event-free survival from death and death and cardiovascular hospitalizations. Cox regression analysis after adjustment for significant predictors demonstrated that microalbuminuria was associated with increase in mortality (hazard ratio, 1.18; 95% confidence interval, 1.18-1.38; P = 0.03) and macroalbuminuria (hazard ratio, 1.33; 95% confidence interval, 1.10-1.61; P < 0.001). Albuminuria was also an independent predictor of death and cardiovascular hospitalizations. Analysis of albuminuria as a continuous parameter (natural logarithm transformed) showed that UACR was an independent predictor of mortality, and cardiovascular hospitalizations. Subclinical albuminuria (UACR 12-29 µg/mg) was directly associated with reduced survival. Cox regression analysis using restricted cubic splines demonstrated an independent continuous increase in mortality with increasing albuminuria (P < 0.0001 adjusted linear model). CONCLUSION: Albuminuria provides important information regarding several detrimental processes in HF and is a significant predictor of a worse outcome.

Long-Term Functional and Structural Durability of Bioprosthetic Valves Placed in the Aortic Valve Position via Percutaneous Rout in Israel.

There is limited organized "real life" data regarding the long-term structural and functional durability of transcatheter aortic valve implants, a topic of major importance. We assessed the 5-year structural and functional integrity outcomes following trans-catheter aortic valve implantation (TAVI) with both self-expandable and balloon-expandable prosthetic valve devices. This study included 450 consecutive patients who underwent TAVI for severe symptomatic aortic stenosis (AS) between September 2008 and December 2011. Data were acquired from a multicenter Israeli registry and the median follow up time was 5.6 years. In 184 patients (40.9%) who survived 5 years, prostheses displayed sustained hemodynamic performance, with average peak and mean aortic valve gradients of 16.2 ± 8.9 and 9.2 ± 6.6 mm Hg, respectively. Late structural valve deterioration was found in 22 (12.3%) patients. Of these, 16 (8.9%) experienced valve deterioration and 6 (3.3%) experienced valve failure. Among the 6 patients with bioprosthetic valve failure, only 3 underwent re-interventions. Bioprosthetic valve dysfunction occurred more frequently in patients with small valves (23 mm) and high peak and mean transvalvular gradients at baseline. In conclusion, a relatively low rate of valve deterioration or failure was noted in our long-term follow-up study after TAVI procedures with both the catheter-based self-expandable and balloon-expandable prosthetic valves.

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.

Low serum albumin: A significant predictor of reduced survival in patients with chronic heart failure.

BACKGROUND: Low serum albumin is common in patients with chronic heart failure (HF). HYPOTHESIS: Albumin may have an impact on clinical outcome in HF. We evaluated the effect of albumin levels on clinical outcome in a real-world cohort of patients with HF. METHODS: All patients with HF at a health maintenance organization were followed for cardiac-related hospitalizations and death. RESULTS: A total of 5779 HF patients were included in the study; mean follow-up was 576 days; median serum albumin was 4.0 g/dL (interquartile range 3.7-4.2), and 12% of the patients had hypoalbuminemia (albumin<3.5 g/dL). Low albumin was associated with increasing age, higher urea and C-reactive protein, lower sodium, hemoglobin, iron, less treatment with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, reduced right ventricular function, and pulmonary hypertension. Cox regression analysis after adjustment for significant predictors demonstrated that decreasing quartiles of albumin was significantly associated with mortality: Lowest quartile compared to highest: hazard ratio (HR) 5.74, 95% confidence interval (CI) 4.08 to 8.07, P < 0.001. Cox regression analysis of albumin as a continuous parameter using restricted cubic splines after adjustment for significant parameters demonstrated that reduced albumin levels were directly associated with increased mortality (P < 0.001 for the adjusted model). Decreasing quartiles of albumin were also a significant predictor of increased cardiac-related hospitalizations. A decrease in albumin on follow-up was an independent predictor of increased mortality by Cox regression analysis: HR 2.58, 95% CI 2.12 to 3.14, P < 0.001. CONCLUSIONS: Low albumin provides important information regarding several detrimental processes in HF and is a significant predictor of a worse outcome in these patients.

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.

Correction: Improvement in cardiac dysfunction with a novel circuit training method combining simultaneous aerobic-resistance exercises. A randomized trial.

[This corrects the article DOI: 10.1371/journal.pone.0188551.].

Clinical Impact of ABO and Rhesus D Blood Type Groups in Patients With Chronic Heart Failure.

Blood group systems based on red blood cell antigens are genetically determined and can identify patients at risk. Type non-O of the ABO blood group system has been associated with coronary artery disease, thrombosis, and a worse prognosis. The present study evaluated the distribution of blood group types in patients with heart failure (HF) and the impact on clinical outcome. We evaluated the ABO and Rhesus D antigen (RhD) blood types in a large cohort of chronic HF patients (n = 3,815). ABO blood type distribution in the HF population was not significantly different to that reported in the general national population (A 40%, B 20%, AB 8%, and O 33%). The percentage of Rh-negative per blood type was also similar (A 10%, B 9%, AB 10%, and O 7%). Patients with type O were more likely to be hypertensive compared with non-O type. Mean follow-up was 4.2 years. Overall survival during follow-up was 55%. Cox regression analysis after adjustment for significant predictors demonstrated that RhD-negative was associated with a worse prognosis in patients with ischemic cardiomyopathy (n = 2,881, 76%): hazard ratio 1.26, 95% confidence interval 1.04 to 1.53, p = 0.02. Type non-O was also independently associated with a worse prognosis compared with type O in patients with non-ischemic cardiomyopathy: hazard ratio 1.32, 95% confidence interval 1.04 to 1.67, p = 0.02. In conclusion, blood group type distribution in HF patients are similar to the general population. RhD-negative is associated with a worse prognosis in patients with ischemic cardiomyopathy.

[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.

Temporal changes in electrocardiographic frontal QRS-T angle and survival in patients with heart failure.

BACKGROUND: Heart failure (HF) is associated with considerable mortality. The electrocardiographic frontal QRS-T angle is a simple parameter to measure, reflects changes in the direction of the repolarization sequence and predicts outcome in patients with HF. Data regarding temporal changes in the frontal QRS-T angle in patients with HF and its impact on outcome is limited. AIM: To evaluate temporal changes in the frontal QRS-T angle and its effect on survival in patients with HF. METHODS: Baseline and follow-up QRS-T angle were calculated from the frontal QRS and T axis of the 12-lead surface electrocardiogram. Patients were followed for survival. RESULTS: 2,929 HF patients were evaluated. Median interval between baseline ECG and follow-up ECG was 895 days, median follow-up time was 1526 days. Overall, the QRS-T angle tended to be stable, with minor changes in the angle over time. The median QRS-T angle change was +3° (IQR -19° to +30°). Overall survival during follow-up was 60%. Cox regression analysis after adjustment for significant predictors demonstrated that the QRS-T angle was an incremental predictor of increased mortality. A widening of the QRS-T angle during follow-up was independently associated with an increase in mortality, evident with an increase of the QRS-T angle difference above 0° (P<0.0001 for the adjusted model). CONCLUSION: QRS-T angle is relatively stable in patients with HF and is a powerful predictor of outcome. Widening of the QRS-T angle has predictive value and is an ominous sign.

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.