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Suboptimal diet is a major modifiable risk factor in cardiovascular disease. Governments, individuals, educational institutes, healthcare facilities and the industry all share the responsibility to improve dietary habits. Healthcare facilities in particular present a unique opportunity to convey the importance of healthy nutrition to patients, visitors and staff. Guidelines on cardiovascular disease do include policy suggestions for population-based approaches to diet in a broad list of settings. Regrettably, healthcare facilities are not explicitly included in this list. The authors propose to explicitly include healthcare facilities as a setting for policy suggestions in the current and future ESC Guidelines for cardiovascular disease prevention in clinical practice. [ABSTRACT FROM AUTHOR]

Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology. Retrospective. University medical center, single institutional. Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015). One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia. Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology. [ABSTRACT FROM AUTHOR]

Abstract Objectives Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves. We present a modification of a relatively simple system introduced in the early 1980s, designated the "Leiden Convention." Methods The first step of the Leiden Convention is that the clinician takes position in the nonfacing sinus of the aorta looking toward the pulmonary orifice. The right-hand facing sinus is sinus 1 , and the left-hand facing sinus is sinus 2. The coronary branches arising from sinus 1 are annotated proceeding in a counterclockwise fashion toward sinus 2. "Usual" (normal) coronary anatomy would be 1R-2LCx. Given their clinical relevance, single sinus coronary arteries are discussed separately. Results This system was originally designed and highly applicable in hearts with an altered great artery relationship, such as in the variable and complicated patterns seen in transposition of the great arteries and double outlet right ventricle. The modified system also can be used in cases with normally related great arteries, cases with single sinus coronary arteries, and cases with bicuspid aortic valves. Conclusions The modified Leiden Convention is not a strict classification but a simple coronary coding system that is broadly applicable. [ABSTRACT FROM AUTHOR]

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Background Vasoplegia is a severe complication that can develop after surgical procedures for heart failure. The current study evaluated the effect of vasoplegia on survival, cardiac function, and renal function 2 years after surgical left ventricular restoration (SVR). Methods Heart failure patients with a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in 2006 to 2014 were included. Vasoplegia was defined as the continuous need of vasopressors (norepinephrine ≥0.2 μg · kg–1 · min–1 or terlipressin [any dose], or both) combined with a cardiac index of 2.2 L · min–1 · m–2 or higher for at least 12 consecutive hours, starting within the first 3 days postoperatively. The effect of vasoplegia on mortality, New York Heart Association Functional Classification, LVEF, and creatinine clearance was assessed up to 2 years of follow-up. Results SVR was performed in 113 patients (80% men), aged 62 ± 10 years, and with an LVEF of 0.25 ± 0.06. Postoperative vasoplegia developed in 23%. Survival was lower in patients with vasoplegia compared with patients without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus 84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and LVEF had improved and were similar in both groups (respectively, p = 0.319 and p = 0.444). Creatinine clearance was lower in patients with vasoplegia compared with patients without vasoplegia 2 years postoperatively (p < 0.001), even after correcting for baseline creatinine clearance (p = 0.009). Conclusions Vasoplegia after SVR is associated with decreased survival. Despite an improved and similar cardiac function, renal function was compromised in vasoplegic patients at the 2-year follow-up. [ABSTRACT FROM AUTHOR]

Background: Noninducibility of ventricular tachycardia (VT) with an equal or longer cycle length (CL) than that of the clinical VT is considered the minimum ablation endpoint in patients with structural heart disease. Because their clinical relevance remains unclear, fast nonclinical VTs are often not targeted. However, an accepted definition for fast VT is lacking. The shortest possible CL of a monomorphic reentrant VT is determined by the ventricular refractory period (VRP).Objective: The purpose of this study was to propose a patient-specific definition for fast VT based on the individual VRP (fVTVRP) and assess the prognostic significance of persistent inducibility after ablation of fVTVRP for VT recurrence.Methods: Of 191 patients with previous myocardial infarction or with nonischemic cardiomyopathy undergoing VT ablation, 70 (age 63 ± 13 years; 64% ischemic) remained inducible for a nonclinical VT and composed the study population. FVTVRP was defined as any VT with CL ≤VRP400 + 30 ms. Patients were followed for VT recurrence.Results: After ablation, 30 patients (43%) remained inducible exclusively for fVTVRP and 40 (57%) for any slower VT. Patients with only fVTVRP had 3-year VT-free survival of 64% (95% confidence interval [CI] 46%-82%) compared to 27% (95% CI 14%-48%) for patients with any slower remaining VT (P = .013). Inducibility of only fVTVRP was independently associated with lower VT recurrence (hazard ratio 0.38; 95% CI 0.19-0.86; P = .019). Among 36 patients inducible for any fVTVRP, only 1 had recurrence with fVTVRP.Conclusion: In patients with structural heart disease, inducibility of exclusively fVTVRP after ablation is associated with low VT recurrence. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effects of MitraClip on left ventricular (LV) and left atrial (LA) myocardial wall stress as assessed with the use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and strain imaging.Methods and Results: Sixty-five patients with symptomatic moderate and severe mitral regurgitation (MR; age 75 ± 9 y, 57% male, 89% functional MR) treated with the use of MitraClip were evaluated. Patients were divided according to 6-month NT-proBNP tertiles. Changes in echocardiographic parameters over 6 months were assessed. Reductions in LV end-diastolic volumes (178 ± 77 mL to 170 ± 79 mL; P = .045) and LV end-systolic volumes (120 ± 70 mL to 111 ± 69 mL; P = .040) were observed in the overall population. Interestingly, low-NT-proBNP-tertile patients showed slight improvements in LV and LA longitudinal strain, whereas high-NT-proBNP-tertile patients showed impairment.Conclusions: Although MitraClip induces hemodynamic unloading in patients with predominantly functional MR, myocardial wall stress is not consistently improved. In patients with reduced NT-proBNP, improvements in LA volume index and LV and LA strains were observed. Patients who showed an increase in NT-proBNP exhibited impairment in LV and LA strain, suggesting an increase of myocardial wall stress. [ABSTRACT FROM AUTHOR]

Background While the overall acute myocardial infarction rates declined in women and men, premature acute myocardial infarction rates remained stable in men and increased in women. Objective The purpose of this study was to assess whether baseline apolipoprotein (apo) levels, clinical characteristics, and follow-up of patients with very premature coronary artery disease (CAD) could provide novel clues for the identification of high-risk individuals. Methods Apos were measured with a validated quantification liquid chromatography–mass spectrometry method in a well-defined cohort of 38 patients aged ≤45 years admitted with acute ST-segment elevation myocardial infarction. Results Mean age was 39.8 ± 4.6 years and 24% was female. Four of these patients (11%) had apoCII levels ≤5.0 mg/L. Compared with the very premature CAD group with apoCII > 5 mg/L, the patients with apoCII levels ≤5.0 mg/L were all females, tended to be younger (35.8 ± 8.4 years vs 40.3 ± 3.9 years, P = .063), had more often a family history of cardiovascular disease ≤65 years ( P = .034) and a significantly lower Framingham risk score ( P = .001). They presented with normal triglyceride levels, and had lower low-density lipoprotein cholesterol, apoB 100 , and apoE levels. Corrected for differences in risk profile, apoCII ≤ 5 mg/L was associated with increased risk of 10-years reinfarction or revascularization (hazard ratio 7.9 [95% confidence interval 1.5–41.6], P = .015). Conclusions In 38 patients with very premature CAD, 11% were found to have low apoCII levels (≤5.0 mg/L) with normal triglyceride levels. Despite their low a priori risk for CAD, these patients presented with ST-segment elevation myocardial infarction and had a high relative risk of 10-year reinfarction or revascularization. This particular phenotype of relatively young female patients with CAD is not recognized earlier and deserves further study. [ABSTRACT FROM AUTHOR]

Background: Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers.Methods and Results: Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca2+-translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting).Conclusions: Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation. [ABSTRACT FROM AUTHOR]

Background—Current methods for predicting adverse events in patients with hypertrophic cardiomyopathy are still limited. Left ventricular global longitudinal strain (GLS) and left atrial volume index (LAVI) have been recently proposed as novel prognostic factors in several cardiovascular diseases. The objective of this study was to evaluate the prognostic value of GLS and LAVI in patients with hypertrophic cardiomyopathy. Methods and Results—Two-dimensional echocardiography was performed in 427 patients with hypertrophic cardiomyopathy (66% men, age 52±15 years), and LAVI and GLS were assessed. During follow-up, the primary end point of all-cause mortality, heart transplantation, sudden cardiac death, and appropriate implantable cardioverter defibrillator therapy was noted. A total of 103 patients reached the primary end point during a follow-up of 6.7 (interquartile range, 3.3–10.0) years. Multivariable Cox regression analysis revealed GLS and LAVI to be independently associated with the primary end point (hazard ratio GLS, 1.10 [1.03–1.19], P=0.007; hazard ratio LAVI, 4.27 [2.35–7.74], P<0.001) after correcting for other clinical variables. When applying the pre-specified cut-off values of 34 mL/m2 for LAVI and −15% for GLS, Kaplan–Meier survival curves showed significant better survival for patients with LAVI <34 mL/m2 (P<0.001) and GLS <−15% (P<0.001) as compared with their counterparts. The likelihood ratio test showed a significant incremental prognostic value of LAVI and GLS (P<0.001) as compared with a model with clinical and standard echocardiographic risk factors. The C-statistic for this model increased from 0.68 to 0.73 when adding GLS and LAVI. Conclusions—GLS and LAVI are independently associated with adverse outcome in patients with hypertrophic cardiomyopathy and may help to optimize risk stratification in these patients. [ABSTRACT FROM AUTHOR]

Objective Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. Methods A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Results Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was −24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). Conclusions Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration. [ABSTRACT FROM AUTHOR]

Background: The value of left atrial (LA) diameter, volume, and strain to risk stratify hypertrophic cardiomyopathy patients for new-onset atrial fibrillation (AF) was explored.Methods and Results: A total of 242 hypertrophic cardiomyopathy patients without AF history were evaluated by (speckle-tracking) echocardiography. During mean follow-up of 4.8±3.7 years, 41 patients (17%) developed new-onset AF. Multivariable analysis showed LA volume (≥37 mL/m2; hazard ratio, 2.68; 95% confidence interval, 1.30-5.54; P=0.008) and LA strain (≤23.4%; hazard ratio, 3.22; 95% confidence interval, 1.50-6.88; P=0.003), but not LA diameter (≥45 mm; hazard ratio, 1.67; 95% confidence interval, 0.84-3.32; P=0.145), as independent AF correlates. Importantly, 59% (n=24) of AF events occurred despite a baseline LA diameter <45 mm, observed in 185 patients. In this patient subset, LA strain (area under the curve 0.73) and LA volume (area under the curve 0.83) showed good predictive value for new-onset AF. Furthermore, patients with LA volume <37 versus ≥37 mL/m2 and LA strain >23.4% versus ≤23.4% had superior 5-year AF-free survival of 93% versus 80% (P=0.003) and 98% versus 74% (P=0.002), respectively. Importantly, LA volume <37 mL/m2 and strain >23.4% yielded high negative predictive value (93% and 98%, respectively) for new-onset AF. Likelihood ratio test indicated incremental value of LA volume assessment (P=0.011) on top of LA diameter to predict new-onset AF in hypertrophic cardiomyopathy patients with LA diameter <45 mm, which tended to increase further by addition of LA strain (P=0.126).Conclusions: LA diameter, volume, and strain all relate to new-onset AF in hypertrophic cardiomyopathy patients. In patients with normal LA size, however, both LA volume and strain further refine risk stratification for new-onset AF. [ABSTRACT FROM AUTHOR]

Background The present study assessed whether descending thoracic aorta growth can be measured reliably by volumetric analysis using multi-detector row computed tomography (MDCT) and whether growth influences the need for future aortic interventions in survivors of acute type A aortic dissection. Methods A total of 51 patients (58 ± 11 years, 61% male) who underwent surgery for type A aortic dissection with ≥2 postoperative MDCT scans ≥5 months apart were included. Volumetric analysis of the descending thoracic aorta was performed with acceptable intraobserver variability. Growth of the complete, false and true lumen was estimated in ml/year and defined as slow growth (≤average growth) or fast growth (>average growth). Results The complete lumen volume increased from 133 ± 8 ml to 163 ± 9 ml after 3.5 years follow-up (p < 0.001), with an average growth rate of 6.1 ml/year. The false lumen volume increased from 81 ± 7 ml to 106 ± 12 ml (p = 0.018) with an average growth rate of 2.8 ml/year. The true lumen changed only slightly from 59 ± 4 ml to 65 ± 8 ml (p = 0.205). Five-year freedom from descending thoracic aorta intervention was significantly lower in patients with above-average growth of the complete lumen (80 ± 9%) compared to slow growth (100%; p = 0.003). Similar observations were made for the false lumen (fast: 74 ± 12% vs. slow: 100%; p = 0.042). Conclusions Increased growth of the false lumen of the descending thoracic aorta after type A aortic dissection was associated with a higher risk of secondary interventions. [ABSTRACT FROM AUTHOR]

Background: There is no consensus about the time instant relative to the J point where ST deviation has to be measured for detection of acute ischemia in the ECG.Methods: We analyzed 53 ECGs, recorded preceding emergency catheterization of acute coronary syndrome patients with a completely occluded culprit artery (cases), and 88 control ECGs recorded in the cardiology outpatient clinic. ECG-amplitude measurements were made every 10 ms, between 20 ms before till 80 ms after the J point. STEMI-detection algorithms varied from the traditional STEMI criterion (elevations in at least two adjacent ECG leads), via the STEMI equivalent criterion (depressions in V2 and V3), to the most liberal STEMI-detection algorithm in which elevations as well as depressions in two adjacent leads were considered as signs of ischemia.Results: Diagnostic accuracy was highest (93.6%) for the most liberal STEMI-detection algorithm at 10 ms after the J point; sensitivity was 94.3% and specificity was 93.2%.Conclusion: The results of our study suggest that STEMI detection close to the J point is optimal. [ABSTRACT FROM AUTHOR]

Background: The aim was to assess the diagnostic value of the Inverse Dower (INVD)-derived vectorcardiogram (VCG) and the Kors-derived VCG to detect elevated systolic pulmonary artery pressure (SPAP) in suspected pulmonary hypertension (PH).Methods: In 132 patients, morphologic variables were evaluated by comparing the VCG parameters synthesized by INVD and Kors matrix. Comparison of the diagnostic accuracy of detecting SPAP ≥50mmHg between the matrices was performed by ROC curve analysis and logistic regression analysis.Results: Most VCG parameters differed significantly between INVD and Kors. ROC analysis for detection of SPAP ≥50mmHg by VG projected on the X-axis demonstrated no difference (p=0.99) between INVD (AUC=0.80) and Kors (AUC=0.80). Both the INVD- and Kors-derived VCG provided significant diagnostic information on the presence of SPAP ≥50mmHg (INVD, OR 1.05, 95%CI 1.03-1.07; P<0.001; Kors, OR 1.05, 95%CI 1.03-1.08; P<0.001).Conclusion: Although there were significant differences in measures of vector morphology, both INVD- and Kors-derived VCG demonstrated equal clinical performance in case of elevated SPAP. [ABSTRACT FROM AUTHOR]

Background It remains unclear whether aortic valve replacement (AVR) has an effect on the aortic root dilatation rate in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The present study evaluated the pre- and postoperative annual aortic root dilatation rates in BAV and TAV. Methods A total of 93 patients (67 ± 11 years; 71% men) who underwent AVR between 2003 and 2013 and had at least 2 pre- and postoperative echocardiographic studies 1 year or more apart were included in this retrospective observational study. The sinus of Valsalva (SOV), sinotubular junction (STJ) and ascending aorta (AAo) were measured in the parasternal long-axis view. Results Patients with BAV (n = 22) were significantly younger and had less coronary artery disease than patients with TAV (n = 71). At all points in time, the aortic root diameters were larger in BAV compared with TAV. Preoperatively, the STJ and AAo grew significantly faster in BAV compared with TAV (STJ, 0.27 versus 0.04 mm/y; p = 0.021; AAo, 0.42 versus 0.15 mm/y; p = 0.019). After operation, there were no significant differences in aortic root dilatation rates between BAV and TAV (SOV, –0.01 versus 0.15 mm/y; p = 0.096; STJ, 0.08 versus 0.05 mm/y; p = 0.676; AAo, 0.28 versus 0.35 mm/y; p = 0.745). Conclusions The annual aortic root dilatation rates were significantly higher in BAV compared with TAV before AVR. However, after AVR, aortic root dilatation rates were similar in BAV and TAV, suggesting an important role of hemodynamics on aortic root dilatation in BAV. [ABSTRACT FROM AUTHOR]

Background: When triaging a patient with acute chest pain at first medical contact, an electrocardiogram (ECG) is routinely made and inspected for signs of myocardial ischemia. The guidelines recommend comparison of the acute and an earlier-made ECG, when available. No concrete recommendations for this comparison exist, neither is known how to handle J-point identification difficulties. Here we present a J-point independent method for such a comparison.Methods: After conversion to vectorcardiograms, baseline and acute ischemic ECGs after 3minutes of balloon occlusion during elective PCI were compared in 81 patients of the STAFF III ECG database. Baseline vectorcardiograms were subtracted from ischemic vectorcardiograms using either the QRS onsets or the J points as synchronization instants, yielding vector magnitude difference signals, ΔH. Output variables for the J-point synchronized differences were ΔH at the actual J point and at 20, 40, 60 and 80ms thereafter. Output variables for the onset-QRS synchronized differences were the ΔH at 80, 100, 120, 140 and 160ms after onset QRS. Finally, linear regressions of all combinations of ΔHJ+… versus ΔHQRS+… were made, and the best combination was identified.Results: The highest correlation, 0.93 (p<0.01), was found between ΔH 40ms after the J point and 160ms after the onset of the QRS complex. With a ΔH ischemia threshold of 0.05mV, 66/81 (J-point synchronized differences) and 68/81 (onset-QRS synchronized differences) subjects were above the ischemia threshold, corresponding to sensitivities of 81% and 84%, respectively.Conclusion: Our current study opens an alternative way to detect cardiac ischemia without the need for human expertise for determination of the J point by measuring the difference vector magnitude at 160ms after the onset of the QRS complex. [ABSTRACT FROM AUTHOR]

Background: Progressive activation delay after premature stimulation has been associated with ventricular fibrillation in nonischemic cardiomyopathy (NICM).Objectives: The objectives of this study were (1) to investigate prolongation of the paced QRS duration (QRSd) after premature stimulation as a marker of activation delay in NICM, (2) to assess its relation to induced ventricular arrhythmias, and (3) to analyze its underlying substrate by late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and endomyocardial biopsy.Methods: Patients with NICM were prospectively enrolled in the Leiden Nonischemic Cardiomyopathy Study and underwent a comprehensive evaluation including LGE-CMR, electrophysiology study, and endomyocardial biopsy. Patients without structural heart disease served as controls for electrophysiology study.Results: Forty patients with NICM were included (mean age 57 ± 14 years; 33 men [83%]; left ventricular ejection fraction 30% ± 13%). After the 400-ms drive train and progressively premature stimulation, the maximum increase in QRSd was larger in patients with NICM than in controls (35 ± 18 ms vs. 23 ± 12 ms; P = .005) and the coupling interval window with QRSd prolongation was wider (47 ± 23 ms vs. 31 ± 14 ms; P = .005). The maximum paced QRSd exceeded the ventricular effective refractory period, allowing for pacing before the offset of the QRS complex in 20 of 39 patients with NICM vs. 1 of 20 controls (P < .001). In patients with NICM, QRSd prolongation was associated with the inducibility of polymorphic ventricular tachycardia (16 of 39 patients) and was related to long, thick strands of fibrosis in biopsies, but not to focal enhancement on LGE-CMR.Conclusion: QRSd is a simple parameter used to quantify activation delay after premature stimulation, and its prolongation is associated with the inducibility of polymorphic ventricular tachycardia and with the pattern of myocardial fibrosis in biopsies. [ABSTRACT FROM AUTHOR]

Background: Ventricular arrhythmias as a result of unintentional blockade of the Kv11.1 (hERG [human ether-à-go-go-related gene]) channel are a major safety concern in drug development. In past years, several highly prescribed drugs have been withdrawn for their ability to cause such proarrhythmia. Here, we investigated whether the proarrhythmic risk of existing drugs could be reduced by Kv11.1 allosteric modulators. Methods and Results: Using [(3)H]dofetilide-binding assays with membranes of human Kv11.1-expressing human embryonic kidney 293 cells, 2 existing compounds (VU0405601 and ML-T531) and a newly synthesized compound (LUF7244) were found to be negative allosteric modulators of dofetilide binding to the Kv11.1 channel, with LUF7244 showing the strongest effect at 10 μmol/L. The Kv11.1 affinities of typical blockers (ie, dofetilide, astemizole, sertindole, and cisapride) were significantly decreased by LUF7244. Treatment of confluent neonatal rat ventricular myocyte (NRVM) monolayers with astemizole or sertindole caused heterogeneous prolongation of action potential duration and a high incidence of early afterdepolarizations on 1-Hz electric point stimulation, occasionally leading to unstable, self-terminating tachyarrhythmias. Pretreatment of NRVMs with LUF7244 prevented these proarrhythmic effects. NRVM monolayers treated with LUF7244 alone displayed electrophysiological properties indistinguishable from those of untreated NRVM cultures. Prolonged exposure of NRVMs to LUF7244 or LUF7244 plus astemizole did not affect their viability, excitability, and contractility as assessed by molecular, immunological, and electrophysiological assays. Conclusions: Allosteric modulation of the Kv11.1 channel efficiently suppresses drug-induced ventricular arrhythmias in vitro by preventing potentially arrhythmogenic changes in action potential characteristics, raising the possibility to resume the clinical use of unintended Kv11.1 blockers via pharmacological combination therapy. [ABSTRACT FROM AUTHOR]

Background: High idiopathic premature ventricular contractions (PVC) burden has been associated with PVC-induced cardiomyopathy. Patients may be symptomatic before left ventricular (LV) dysfunction develops. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and circumferential end-systolic wall stress (cESS) on echocardiography are markers for increased ventricular wall stress. This study aimed to evaluate the relation between presenting symptoms, PVC burden, and increased ventricular wall stress in patients with frequent PVCs and preserved LV function.Methods and Results: Eighty-three patients (41 men; 49±15 years) with idiopathic PVCs and normal LV function referred for PVC ablation were included. Type of symptoms (palpitations, fatigue, and [near-]syncope), PVC burden on 24-hour Holter, NT-proBNP levels, and cESS on echocardiography were assessed before and 3 months after ablation. Sustained successful ablation was defined as ≥80% PVC burden reduction during follow-up. Patients were symptomatic for 24 months (Q1-Q3, 16-60); 73% reported palpitations, 47% fatigue, and 30% (near-)syncope. Baseline PVC burden was 23±13%, median NT-proBNP 92 pg/mL (Q1-Q3 50-156), and cESS 143±35 kdyne/cm(2). Fatigue was associated with higher baseline NT-proBNP and cESS (P<0.001, P=0.011, respectively). After sustained successful ablation, achieved in 81%, NT-proBNP and cESS decreased significantly (P<0.001 and P=0.036, respectively). Fatigue was independently associated with a significantly larger reduction in NT-proBNP. In patients with nonsuccessful ablation, NT-proBNP and cESS remained unchanged.Conclusions: In patients with frequent PVCs and preserved LV function, fatigue was associated with higher baseline NT-proBNP and cESS, and with a significantly larger reduction in NT-proBNP after sustained successful ablation. These findings support a link between fatigue and PVC-induced increased ventricular wall stress, despite preserved LV function. [ABSTRACT FROM AUTHOR]