A different cardiac resynchronization therapy technique might be needed in some patients with nonspecific intraventricular conduction disturbance pattern.

BACKGROUND: Current cardiac resynchronization therapy (CRT), devised to eliminate dyssynchrony in left bundle branch block (LBBB), works by pacing the latest activated left ventricular site (LALVS). We hypothesized that patients with nonspecific intraventricular conduction disturbance (NICD) pattern respond less favorably to CRT, because their LALVS is far away from that in LBBB. METHODS: By measuring the amplitude and polarity of secondary ST-segment alterations in two optional frontal and horizontal surface electrocardiogram (ECG) leads and using a software, we determined the resultant 3D spatial secondary ST vector, which is directed 180o away from the LALVS, in 110 patients with LBBB pattern and 77 patients with NICD pattern and heart failure. To validate the ECG method, we also estimated the LALVS by echocardiography using 3D parametric imaging and 2D speckle tracking in 22 LBBB patients and 20 NICD patients. Patients with NICD pattern were subdivided according to their non-overlapping frontal plane resultant secondary ST vector ranges to the NICD-1 subgroup (n = 44) and the NICD-2 subgroup (n = 33). RESULTS: Based on the software determined coordinates of the resultant 3D spatial secondary ST vector directed 180o away from the LALVS, the LALVSs were located leftward, posterosuperior in the LBBB group, slightly left, superior in the NICD-1 subgroup, and slightly left, posteroinferior in the NICD-2 subgroup. The LALVS determined by ECG and echocardiography matched in all patients, except two. CONCLUSIONS: In the NICD-2 subgroup, a remote LALVS was found from that in LBBB pattern, which might explain the high non-response rate of the NICD pattern to the current CRT technique.

Novel electrocardiographic dyssynchrony criteria improve patient selection for cardiac resynchronization therapy.

Aims: We hypothesized that the greater the intra- or interventricular dyssynchrony (intraD, interD), the more effective cardiac resynchronization therapy (CRT) is. We sought to improve patient selection for CRT by using novel ECG dyssynchrony criteria. Methods and results: Left ventricular (LV) intraD was estimated by the absolute time difference between the intrinsicoid deflections (ID) in leads aVL and aVF divided by the QRS duration (QRSd): [aVLID - aVFID]/QRSd (%). InterD was estimated from the formula: [V5ID - V1ID]/QRSd (%). Their >25% value indicated electrical dyssynchrony present (ED+) and ≤25% value electrical dyssynchrony absent (ED-) diagnoses. Using the intraD + interD criteria (intra + interDC) together, if at least one of them indicated ED+ diagnosis, a final ED+ diagnosis, if both indicated ED- diagnosis, a final ED- diagnosis was made. Two authors, blinded to CRT response, retrospectively analysed pre-CRT ECGs of 124 patients with known CRT outcome. CRT response was defined as improvement of ≥ 1 NYHA class, being alive and having no hospitalizations for heart failure during 6 months of follow-up. 35/124 (28%) patients were non-responders (NRs), using the traditional criteria (TC) correct diagnosis was made in the remaining 89/124 (72%) responder (R) cases. The test accuracy (TA) of intra + interDC + TC [100/124 (81%), P < 0.001] was superior to that of TC [89/124 (72%)] due to its superior TA [36/43 (84%) vs. 29/43 (67%), respectively, P = 0.0156] in the non-specific intra-ventricular conduction disturbance (NICD) subgroup [43/124 (35%)]. In the left bundle branch block subgroup [70/124 (56%)] there was no between-criteria difference in TA. Conclusion: The intra + interDC + TC predicts clinical response after CRT more accurately than TC alone, due to greater TA in the NICD subgroup.

The role of electrocardiography in the elaboration of a new paradigm in cardiac resynchronization therapy for patients with nonspecific intraventricular conduction disturbance.

Cardiac resynchronization therapy (CRT) is associated with a favorable outcome only in patients with left bundle branch block (LBBB) pattern and in patients with a QRS duration > 150 ms, in patients with non-LBBB pattern with a QRS duration of 120-150 ms usually is not beneficial. After adjusting for QRS duration, QRS morphology was no longer a determinant of the clinical response to CRT. In contrast to the mainstream view, we hypothesized that the unfavorable CRT outcome in patients with non-LBBB and a QRS duration of 120-150 ms is not due to the QRS morphology itself, but to less dyssynchrony and unfavorable patient characteristics in this subgroup, such as more ischemic etiology and greater prevalence of male patients compared with patients with LBBB pattern. Further, the current CRT technique is devised to eliminate the dyssynchrony present in patients with LBBB pattern and inappropriate to eliminate the dyssynchrony in patients with non-LBBB pattern. We also hypothesized that electrocardiography may also provide information about the presence of interventricular and left intraventricular dyssynchrony and the approximate location of the latest activated left ventricular (LV) region. To this end, we devised new ECG criteria to estimate interventricular and LV intraventricular dyssynchrony and the approximate location of the latest activated LV region. Our preliminary data demonstrated that the latest activated LV region in patients with nonspecific intraventricular conduction disturbance (NICD) pattern might be at a remote site from that present in patients with LBBB pattern, which might necessitate the invention of a novel CRT technique for patients with NICD pattern. The application of the new interventricular and LV intraventricular dyssynchrony ECG criteria and a potential novel CRT technique might decrease the currently high nonresponder rate in patients with NICD pattern.

Genetic predisposition in patients with hypertension and normal ejection fraction to oxidative stress.

The role of oxidative stress (OXS) due to myocardial nitric oxide synthase (NOS) uncoupling related to oxidative depletion of its cofactor tetrahydrobiopterin (BH4) emerged in the pathogenesis of heart failure with preserved ejection fraction. We determined the prevalence of six single nucleotide polymorphisms (SNPs) of genes encoding enzymes related to OXS, BH4 metabolism, and NOS function in ≥60-year-old 94 patients with hypertension and 18 age-matched controls with normal ejection fraction. Using echocardiography, 56/94 (60%) patients with hypertension had left ventricular (LV) diastolic dysfunction (HTDD+ group) and 38/94 (40%) patients had normal LV diastolic function (HTDD- group). Four SNPs (rs841, rs3783641, rs10483639, and rs807267) of guanosine triphosphate cyclohydrolase-1, the rate-limiting enzyme in BH4 synthesis, one (rs4880) of manganese superoxide dismutase, and one (rs1799983) of endothelial NOS genes were genotyped using real-time polymerase chain reaction method and Taqman probes. Protein carbonylation, BH4, and total biopterin levels were measured from plasma samples. No between-groups difference in minor allele frequency of SNPs was found. We calculated a genetic score indicating risk for OXS based on the minor allele frequencies of the SNPs. A high genetic risk for OXS was significantly associated with HTDD+ even after adjustment for confounding variables (odds ratio [95% confidence interval]:4.79 [1.12-20.54]; P = .035). In both patient groups protein carbonylation (P < .05 for both), plasma BH4 (P < .01 for both) and in the HTDD+ group total biopterin (P < .05) increased versus controls. In conclusion, in patients with hypertension and normal ejection fraction, a potential precursor of heart failure with preserved ejection fraction, a partly genetically determined increased OXS, seems to be associated with the presence of LV diastolic dysfunction.

The mechanism of reduced longitudinal left ventricular systolic function in hypertensive patients with normal ejection fraction.

BACKGROUND: MacIver and Townsend's hypothesis predicts, based on a mathematical model of left ventricular contraction, that preserved absolute radial wall thickening (radWT) due to left ventricular hypertrophy is responsible for the normal ejection fraction in patients with heart failure with preserved ejection fraction (HFPEF). METHODS: We tested the validity of this hypothesis by detailed echocardiography including evaluation of ventricular myocardial strain (S) using speckle tracking imaging in at least 60-year-old 18 controls and 94 hypertensive patients with normal ejection fraction. RESULTS: Echocardiography revealed no left ventricular diastolic dysfunction in 38 out of 94 (40%) patients with hypertension (HTDD-negative group), and 56 out of 94 (60%) patients had diastolic dysfunction (HTDD-positive groups). The absolute values of global longitudinal left ventricular peak systolic S were significantly reduced in both patient groups (P < 0.05 for HTDD-negative, P < 0.01 for HTDD-positive groups) vs. the controls. There were no significant between-groups differences in circumferential and radial peak left ventricular systolic Ss, radWT and ejection fraction. Left ventricular mass (LVM) (P < 0.001), LVM/BMI (P < 0.01) increased in the HTDD-positive group and ejection fraction/LVM/BMI decreased in both patient groups (P < 0.01 for HTDD-negative, P < 0.001 for HTDD-positive groups) vs. the controls. LVM increased, ejection fraction/LVM/BMI decreased in the HTDD-positive group vs. the HTDD-negative group (P < 0.05 and P < 0.01, respectively). CONCLUSION: We demonstrated decreased longitudinal left ventricular systolic function and showed that preserved ejection fraction was due to preserved absolute radWT and not due to increased radial or circumferential systolic function in patients with hypertension and normal ejection fraction, a potential HFPEF precursor condition. Instead of ejection fraction, rather ejection fraction/LVM/BMI might be used to detect subtle left ventricular systolic dysfunction in hypertension and HFPEF.

Inflammation and oxidative stress caused by nitric oxide synthase uncoupling might lead to left ventricular diastolic and systolic dysfunction in patients with hypertension.

OBJECTIVE: To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction (HFPEF). METHODS: We performed echocardiography for 112 patients (≥ 60 years old) with normal EF (18 controls and 94 with hypertension), and determined protein carbonylation (PC), and tetrahydrobiopterin (BH4), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fibrinogen, plasminogen activator inhibitor type-I (PAI-I), von Willebrand factor, chromogranin A (cGA) and B-type natriuretic peptide (BNP) levels from their blood samples. RESULTS: We found that 40% (38/94) of the patients with hypertension (HT) had no diastolic dysfunction (HTDD-), and 60% (56/94) had diastolic dysfunction (HTDD+). Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD+ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventricular (LV) systolic and diastolic myocardial deformation (strain and strain rate) was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. CONCLUSIONS: In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of HT to HFPEF.

Comparison of the "real-life" diagnostic value of two recently published electrocardiogram methods for the differential diagnosis of wide QRS complex tachycardias.

OBJECTIVES: The diagnostic values of the aVR lead or "Vereckei algorithm," and the lead II R-wave peak time (RWPT) criterion, recently devised for the differential diagnosis of wide QRS complex tachycardias (WCTs), were compared. METHODS: A total of 212 WCTs (142 ventricular tachycardias [VTs], 62 supraventricular tachycardias [SVT], and eight preexcitation SVTs) from 145 patients with proven electrophysiologic diagnoses were retrospectively analyzed by seven examiners blinded to the electrophysiologic diagnoses. RESULTS: The overall test accuracy of the Vereckei algorithm was superior to that of the RWPT criterion (84.3% vs. 79.6%; p = 0.0003). The sensitivity of the Vereckei algorithm for VT diagnosis was greater than that of RWPT criterion (92.4% vs. 79.1%; p < 0.0001). The negative predictive value (NPV) for the Vereckei algorithm was also greater (77.8%; 95% confidence interval [CI] = 73.6% to 82.1%) than that of the RWPT criterion (61.6%; 95% CI = 57.6% to 65.6%). The specificity of the Vereckei algorithm was lower than that of the RWPT criterion (64.7% vs. 80.9%; p < 0.0001). The positive predictive value (PPV) was also lower for the Vereckei algorithm (86.4%; 95% CI = 84.4% to 88.4%) than for the RWPT criterion (90.9%; 95% CI = 89.1% to 92.8%). Incorrect diagnoses made by the Vereckei algorithm were mainly due to misdiagnosis of SVT as VT (65.7% of cases), and those made by the RWPT criterion were due to the more dangerous misdiagnosis of VT as SVT (72.5% of cases). CONCLUSIONS: The Vereckei algorithm was superior in overall test accuracy, sensitivity, and NPV for VT diagnosis and inferior in specificity and PPV to the RWPT criterion. All of these parameters were lower in "real life" than those reported by the original authors for each of the particular electrocardiographic methods.