Kynurenic acid, a key L-tryptophan-derived metabolite, protects the heart from an ischemic damage.

BACKGROUND: Renal injury induces major changes in plasma and cardiac metabolites. Using a small- animal in vivo model, we sought to identify a key metabolite whose levels are significantly modified following an acute kidney injury (AKI) and to analyze whether this agent could offer cardiac protection once an ischemic event has occurred. METHODS AND RESULTS: Metabolomics profiling of cardiac lysates and plasma samples derived from rats that underwent AKI 1 or 7 days earlier by 5/6 nephrectomy versus sham-operated controls was performed. We detected 26 differential metabolites in both heart and plasma samples at the two selected time points, relative to sham. Out of which, kynurenic acid (kynurenate, KYNA) seemed most relevant. Interestingly, KYNA given at 10 mM concentration significantly rescued the viability of H9C2 cardiac myoblast cells grown under anoxic conditions and largely increased their mitochondrial content and activity as determined by flow cytometry and cell staining with MitoTracker dyes. Moreover, KYNA diluted in the drinking water of animals induced with an acute myocardial infarction, highly enhanced their cardiac recovery according to echocardiography and histopathology. CONCLUSION: KYNA may represent a key metabolite absorbed by the heart following AKI as part of a compensatory mechanism aiming at preserving the cardiac function. KYNA preserves the in vitro myocyte viability following exposure to anoxia in a mechanism that is mediated, at least in part, by protection of the cardiac mitochondria. A short-term administration of KYNA may be highly beneficial in the treatment of the acute phase of kidney disease in order to attenuate progression to reno-cardiac syndrom and to reduce the ischemic myocardial damage following an ischemic event.

Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing.

Background: We aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET). Methods: Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex. Results: One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction). Conclusions: Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.

[RECOMMENDATIONS FOR CHANGING CARDIOVASCULAR SCREENING OF ATHLETES WHO ARE REQUIRED FOR PRE-PARTICIPATION SCREENING UNDER THE SPORTS LAW - A POSITION PAPER ON BEHALF OF THE ISRAEL HEART SOCIETY].

INTRODUCTION: For many years routine screening of athletes in Israel includes frequently performed ECGs and exercise tests that overload the system with questionable benefits. The purpose of the current document is to reevaluate the need for pre-participation testing and establish new evidence-based guidelines. It should be noted that our proposal for a change of approach relates only to subjects whose health questionnaire is normal, who do not have a family history of sudden and unexpected death at an early age, or a family history of hereditary heart disease and whose physical examination from a cardiovascular point of view is normal.

Heart Failure Due to High-Degree Atrioventricular Block: How Frequent Is It and What Is the Cause?

BACKGROUND: The causes of heart failure (HF) during high-grade atrioventricular block (AVB) are poorly understood. This study assessed the mechanisms of HF in patients with AVB. METHODS: We studied patients presenting (between 2012 and 2016) with high-grade AVB not related to acute myocardial infarction. Patients with preexisting significant valvular heart disease were excluded. All patients underwent comprehensive echocardiographic evaluation during AVB, before pacemaker implantation. The diagnosis of HF was based on the Framingham criteria. RESULTS: A total of 122 patients were included in the study, 50% male, average age 76 ± 13 years. Twenty-eight patients (23%) with AVB presented with HF. Univariate correlates associated with HF were decrease in cardiac output (CO) (odds ratio [OR] 0.68 [95% confidence interval 0.49-0.9] per L/min; P = 0.007), measures of impaired left ventricular (LV) compliance, and increase in diastolic mitral regurgitation (MR) volume (OR 1.04 [1.01-1.07] per cc; P = 0.0016). Ventricular rate during AVB and LV ejection fraction were not significantly associated with the presence of HF. By multivariate nominal logistic analysis, the best model associated with HF included diastolic MR volume (OR 1.04 [1.001-1.09]; P = 0.02), A-wave deceleration time (OR 0.96 [0.94-0.9]; P = 0.001), and CO (OR 0.92 [0.4-1.00]; P = 0.005) (χ2 = 30.6; area under the receiver operating characteristic curve = 0.84; P < 0.0001 for the entire model). CONCLUSIONS: In the setting of high-degree AVB, clinical HF occurrence correlates with impaired LV compliance and diastolic MR volume, but not with heart rate or LV ejection fraction. The cardiac performance of patients with poor LV compliance and high-volume diastolic MR may show maladjustment to slow heart rates, manifesting as low CO and HF.

Combined Echocardiographic and Cardiopulmonary Exercise to Assess Determinants of Exercise Limitation in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Current methods do not allow a thorough assessment of causes associated with limited exercise capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty patients with COPD and 20 matched control subjects were assessed using combined cardiopulmonary and stress echocardiographic testing. Various echocardiographic parameters (left ventricular [LV] volumes, right ventricular [RV] area, ejection fraction, stroke volume, S', and E/e' ratio) and ventilatory parameters (peak oxygen consumption [Vo2] and A-Vo2 difference) were measured to evaluate LV and RV function, hemodynamics, and peripheral oxygen extraction (A-VO2 difference). RESULTS: Significant differences (both between groups and for group-by-time interaction) were seen in exercise responses (LV volume, RV area, LV volume/RV area ratio, S', E/e' ratio, tricuspid regurgitation grade, heart rate, stroke volume, and Vo2). The major mechanisms of reduced exercise tolerance in patients with COPD were bowing of the septum to the left in 12 (60%), abnormal increases in E/e' ratio in 12 (60%), abnormal stroke volume reserve in 16 (80%), low peak A-Vo2 difference in 10 (50%), chronotropic incompetence in 13 (65%), or a combination of several mechanisms. Patients with COPD and poor exercise tolerance showed attenuated increases in stroke volume, heart rate, and A-Vo2 difference and exaggerated changes in LV/RV ratio and LV compliance (ratio of LV volume to E/e' ratio) compared with patients with COPD with good exercise tolerance. CONCLUSIONS: Combined cardiopulmonary and stress echocardiographic testing can be helpful in determining individual mechanisms of exercise intolerance in patients with COPD. In patients with COPD, exercise intolerance is predominantly the result of chronotropic incompetence, limited stroke volume reserve, exercise-induced elevation in left filling pressure, and peripheral factors and not simply obstructive lung function. Limited stroke volume is related to abnormal RV contractile reserve and reduced LV compliance introduced through septal flattening and direct ventricular interaction.

Re-Appraisal of Echocardiographic Assessment in Patients with Pulmonary Embolism: Prospective Blinded Long-Term Follow-Up.

BACKGROUND: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease. OBJECTIVES: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE. METHODS: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results. RESULTS: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function. CONCLUSIONS: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Correction: Cardiac remodeling secondary to chronic volume overload is attenuated by a novel MMP9/2 blocking antibody.

[This corrects the article DOI: 10.1371/journal.pone.0231202.].

Cardiac remodeling secondary to chronic volume overload is attenuated by a novel MMP9/2 blocking antibody.

OBJECTIVE: Monoclonal antibody derivatives are promising drugs for the treatment of various diseases due to their high matrix metalloproteinases (MMP) active site specificity. We studied the effects of a novel antibody, SDS3, which specifically recognizes the mature active site of MMP9/2 during ventricular remodeling progression in a mouse model of chronic volume overload (VO). METHODS: VO was induced by creating an aortocaval fistula (ACF) in 10- to 12-week-old C57BL male mice. The VO-induced mice were treated with either vehicle control (PBS) or with SDS3 twice weekly by intraperitoneal (ip) injection. The relative changes in cardiac parameters between baseline (day 1) and end-point (day 30), were evaluated by echocardiography. The effects of SDS3 treatment on cardiac fibrosis, cardiomyocyte volume, and cardiac inflammation were tested by cardiac staining with Masson's trichrome, wheat Germ Agglutinin (WGA), and CD45, respectively. Serum levels of TNFα and IL-6 with and without SDS3 treatment were tested by ELISA. RESULTS: SDS3 significantly reduced cardiac dilatation, left ventricular (LV) mass, and cardiomyocyte hypertrophy compared to the vehicle treated animals. The antibody also reduced the heart-to-body weight ratio of the ACF animals to values comparable to those of the controls. Interestingly, the SDS3 group underwent significant reduction of cardiac inflammation and pro-inflammatory cytokine production, indicating a regulatory role for MMP9/2 in tissue remodeling, possibly by tumor necrosis factor alpha (TNFα) activation. In addition, significant changes in the expression of proteins related to mitochondrial function were observed in ACF animals, these changes were reversed following treatment with SDS3. CONCLUSION: The data suggest that MMP9/2 blockage with SDS3 attenuates myocardial remodeling associated with chronic VO by three potential pathways: downregulating the extracellular matrix proteolytic cleavage, reducing the cardiac inflammatory responses, and preserving the cardiac mitochondrial structure and function.

Neutrophil Gelatinase-Associated Lipocalin for the Early Prediction of Acute Kidney Injury in ST-Segment Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention.

INTRODUCTION AND OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI). METHODS: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range. RESULTS: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p < 0.001) and 24 h (142 ± 41 vs. 93 ± 36; p < 0.001). Per ROC curve analysis, an optimal cutoff value of NGAL (>120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801-0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013-1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001-1.036; p = 0.04). CONCLUSIONS: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Potential roles in cardiac physiology and pathology of the cation channel TRPV2 expressed in cardiac cells and cardiac macrophages: a mini-review.

TRPV2 is a well-conserved channel protein expressed in almost all tissues. Cardiomyocyte TRPV2 is expressed in the intercalated disks of the cardiac sarcomeres, where it is involved in maintaining the proper mechanoelectric coupling and structure. It is also abundantly expressed in the intracellular pools, mainly the endoplasmic reticulum. Under pathological conditions, TRPV2 is translocated to the sarcolemma, where it mediates an abnormal [Ca]2+ entry that may contribute to disease progression. In addition, an intracellularly diffused TRPV2 expression is present in resident cardiac macrophages. Upon infection or inflammation, TRPV2 is engaged in early phagosomes and is, therefore, potentially involved in protecting the cardiac tissue. Following acute myocardial infarction, a profound elevated expression of TRPV2 is observed on the cell membrane of the peri-infarct macrophages. The macrophage TRPV2 may harbor a detrimental effect in cardiac recovery by increasing unfavorable migration and phagocytosis processes in the injured heart. Most reports suggest that while cardiac TRPV2 activation may be beneficial under specific physiological conditions, both cardiac- and macrophage-related TRPV2 blocking can significantly ameliorate disease progression in various pathological states. To verify this possibility, the time frame of TRPV2 overexpression and its mediated signaling need to be fully characterized in both cardiomyocyte and cardiac macrophage populations.

Acute kidney injury after transcatheter aortic valve implantation and mortality risk-long-term follow-up.

BACKGROUND: Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up. METHODS: This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis. RESULTS: The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35-10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30-2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022). CONCLUSIONS: Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.

Outcomes of early and reversible renal impairment in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention.

OBJECTIVE: Acute kidney injury (AKI) is a frequent complication in patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). While AKI occurring post-PCI has been well studied, the incidence and clinical significance of early renal impairment evident on hospital admission prior to PCI and which resolves towards discharge has not been investigated. METHODS: We retrospectively studied 2339 STEMI patients treated with primary PCI. The incidence of renal impairment and in-hospital complications as well as short and long-term mortality were compared between patients who did not develop renal impairment, patients who developed post-PCI AKI and those who presented with renal impairment on admission but improved their renal function during hospitalization (improved renal function). Improved renal function was defined as continuous and gradual decrease of ⩾ 0.3 mg/dL in serum creatinine levels obtained at hospital admission. RESULTS: One hundred and nineteen patients (5%) had improved renal function and 230 patients (10%) developed post-PCI AKI. When compared with patients with no renal impairment, improved renal function and post-PCI AKI were associated with more complications and adverse events during hospitalization as well as higher 30-day mortality. Long-term mortality was significantly higher among those with post-PCI AKI (63/230, 27%) following STEMI than those without renal impairment (104/1990, 5%; p<0.001), but there was no significant difference in long term mortality between patients with no renal impairment and those with improved renal function (5% vs. 7.5%, p=0.17). CONCLUSION: In STEMI patients undergoing primary PCI, the presence of renal impairment prior to PCI which resolves towards discharge is not uncommon and is associated with adverse short-term outcomes but better long-term outcomes compared with post-PCI AKI.

Tricuspid regurgitation and long-term clinical outcomes.

AIMS: Tricuspid regurgitation (TR) is a frequent echocardiographic finding; however, its effect on outcome is unclear. The objectives of current study were to evaluate the impact of TR severity on heart failure hospitalization and mortality. METHODS AND RESULTS: We retrospectively reviewed consecutive echocardiograms performed between 2011 and 2016 at the Tel-Aviv Medical Center. TR severity was determined using semi-quantitative approach including colour jet area, vena contracta width, density of continuous Doppler jet, hepatic vein flow pattern, trans-tricuspid inflow pattern, annular diameter, right ventricle, and right atrial size. Major comorbidities, re-admissions and all-cause mortality were extracted from the electronic health records. The final analysis included 33 305 patients with median follow-up period of 3.34 years (interquartile range 2.11-4.54). TR (≥mild) was present in 31% of our cohort. One-year mortality rates were 7.7% for patients with no/trivial TR, 16.8% for patients with mild TR, 29.5% for moderate TR, and 45.6% for patients with severe TR (P < 0.001). Univariate and multivariate analyses demonstrated a positive correlation between TR severity and overall mortality and rates of heart failure re-admission after adjustment for potential confounders. The proportional hazards method for overall mortality showed that patients with moderate [hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.02-1.3, P = 0.024] and severe TR (HR 1.43, 95% CI 1.08-1.88, P = 0.011) had a worse prognosis than those with no or minimal TR. CONCLUSIONS: The presence of any degree of TR is associated with adverse clinical outcome. At least moderate TR is independently associated with increased mortality.

Elevated neutrophil gelatinase-associated lipocalin levels before contrast media administration among ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released by renal tubular cells upon nephrotoxic or ischemic events and is considered an early marker of tubular damage. We aimed to demonstrate the presence of early renal injury detected by elevated NGAL levels taken before contrast administration in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). PATIENTS AND METHODS: We prospectively included 88 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (baseline NGAL; NGAL1) and 24 h after PCI (NGAL2). Abnormal elevations in NGAL levels were defined using the cardiac surgery associated NGAL score (NGAL score) with NGAL levels at least 100 ng/ml, suggesting renal tubular damage. Patients were also assessed for the dynamics between NGAL2 and NGAL1 levels. RESULTS: The mean age of the patients was 62 ± 13 years and 78% were men. A total of 50/88 (56%) patients had baseline NGAL level of at least 100, suggesting possible tubular damage before PCI. Only 10 patients progressed to clinical acute kidney injury during hospitalization, all of whom had baseline NGAL level of at least 100 (P < 0.001). Among patients with baseline NGAL at least 100, 28/50 (56%) showed a decrease in the NGAL level within 24 h, whereas only 9/50 (18%) showed an elevation in the NGAL level. In contrast, only 7/38 (19%) patients with baseline NGAL level less than 100 showed an elevation in NGAL levels within 24 h. CONCLUSION: Elevated NGAL levels before primary PCI suggesting renal tubular damage are common among STEMI patients. Further trials are needed to assess the complex cardio-renal interactions.

Quantitative assessment of effective regurgitant orifice: impact on risk stratification, and cut-off for severe and torrential tricuspid regurgitation grade.

AIMS: Asses the added value of quantitative evaluation of tricuspid regurgitation (TR), the proper cut-off value for severe TR and 'torrential TR' based on outcome data. The added value of quantitative evaluation of TR, and the cut-off values associated with increased mortality are unknown. METHODS AND RESULTS: In patients with all-cause TR assessed both qualitatively and quantitatively by proximal iso-velocity surface area method, long-term and 1-year outcome analysis was conducted. Thresholds for excess mortality were assessed using spline curves, receiver-operating characteristic curves, and minimum P-value analysis. The study involved 676 patients with all-cause TR (age 73.9 ± 14 years, male 45%, ejection fraction 52.9 ± 14%). Effective regurgitant orifice (ERO) was strongly associated with decreased survival in unadjusted [hazard ratio (HR) 2.38 (1.79-3.01), P < 0.0001 per 0.1 cm2 increment] and adjusted [2.6 (1.25-5.0), P = 0.01] analyses. Quantitative grading was superior to qualitative grading in prediction of outcome (P < 0.01). The optimal cut-off value for the best separation in survival between groups of patients with severe vs. lesser degree of TR was 0.35 cm2 [P < 0.0001, HR =2.0 (1.5-2.7)]. ERO negatively impacted survival, even when including only the subgroup of patients with severe TR [HR 1.5 (1.01-2.3); P = 0.04]. The optimal threshold corresponding for the best separation for survival between groups of patients with severe vs. 'torrential' TR was 0.7 cm2 [P = 0.005, HR =2.6 (1.2-5.1)]. CONCLUSION: TR can be severe and even 'torrential' and is associated with excess mortality. Quantitative assessment of TR by ERO measurement is a powerful independent predictor of outcome, superior to standard qualitative assessment. The optimal cut-off above which mortality is increased is 0.35 cm2, similar albeit slightly lower than suggested in recent guidelines. Torrential TR >0.7 cm2 is associated with poorer survival compared to patients with severe TR (ERO > 0.4 cm2 and <0.7 cm2).

Clinical impact of post procedural mitral regurgitation after transcatheter aortic valve replacement.

BACKGROUND: While the impact of mitral regurgitation (MR) prior to transcatheter aortic valve replacement (TAVR) has been intensively studied, the implications of post-procedural MR on outcome are unknown. We investigated the clinical and physiological impact of significant MR after TAVR. METHODS: Clinical and echocardiographic data of 486 patients who underwent TAVR between March 2009 and December 2014 were evaluated. Clinical endpoints included overall mortality and combined endpoint of mortality, heart failure re-hospitalization and new atrial fibrillation. Echocardiographic parameters were analyzed at baseline, 30-day and 6-month after TAVR. RESULTS: MR severity improved in 25%, worsened in 19% and did not change in 56% of patients 30-days post TAVR (p = 0.3). Post TAVR MR grade ≥ moderate was present in 16.1%. Predictive accuracy of post TAVR MR was low (AUC = 0.63). Median follow-up was 4.3 years (interquartile range, 2.5 to 6.1). Post TAVR MR grade ≥ moderate was associated with increased mortality and combined cardiac events (p = 0.013 and p < 0.001) even when adjusted for all clinical and echo parameters and when analyzed with propensity score matching. In patients with MR ≥ moderate, LV filling pressure and RV hemodynamics worsened 6 months post TAVR, while improving in patients with less significant post procedural MR. CONCLUSION: Post procedural, but not pre-procedural MR grade ≥ moderate was independently associated with mortality and adverse cardiac events after TAVR. Significant MR post TAVR resulted in adverse LV and RV remodeling and poor hemodynamic. Our study strengthens the rational for initiating early treatment to reduce post TAVR MR.

Incidence, characteristics and outcomes in very young patients with ST segment elevation myocardial infarction.

OBJECTIVE: ST-segment elevation acute myocardial infarction (STEMI) in very young adults is uncommon. Many studies have focused on the cutoff of 45-50 years old to define young patients with STEMI leaving limited data on the group of very young patients aged less than 35 years old. We investigated the incidence of STEMI in different subgroups of young patients and focused on the characteristics, possible pathogenesis and outcomes in very young patients aged less than 35 years old. METHODS: We retrospectively studied 792 STEMI patients aged less than 55 years who underwent successful primary PCI. We categorized patients as very young if they were or less 35 years old and as young if they were between 36 and 55 years old. Baseline characteristics, angiographic findings, as well as short- and long-term outcomes were compared between the two groups. RESULTS: There were 46 (6%) very young patients (age ≤ 35 years) and 748 (94%) young patients (36 < age ≤ 55 years). Very young patients had fewer atherosclerotic risk factors than young patients, but there was no difference in short- or long-term outcomes. Overt hypercoagulable state was evident serologically (antiphospholipid antibodies) in 2/7 (29%) of screened patients and clinically (left ventricular thrombus or acute coronary thrombosis without an atherosclerotic plaque) in 6/46 patients (13%). CONCLUSION: Very young patients with STEMI constitute a distinct subset of young patients with fewer atherosclerotic risk factors yet comparable outcomes. More efforts should be made screening for serologic and clinical evidence of hypercoagulability in this group of patients.