Simple Electrocardiographic Score Can Predict Left Ventricular Reverse Remodeling in Patients With Non-Ischemic Cardiomyopathy.

Background: Left ventricular reverse remodeling (LVRR) is a favorable response in non-ischemic, non-valvular cardiomyopathy (NICM) patients. Recently, 18-lead body surface electrocardiography (ECG), the standard 12-lead ECG with synthesized right-sided/posterior chest leads, has been developed, but its predictive value for LVRR has not been evaluated. Methods and Results: Of 216 consecutive hospitalized NICM patients with LV ejection fraction (LVEF) ≤35%, we studied 125 who received optimization of their heart failure treatment and had 18-lead ECG and echocardiography data available for evaluating LVRR, defined as an absolute increase in LVEF ≥10% concomitant with LVEF ≥35% after 1-year optimized treatment. Most 18-lead ECG parameters in the NICM patients differed from those in 312 age- and body mass index-matched subjects with normal echocardiography. LVRR occurred in 59 NICM patients and they had a larger QRS amplitude in the limb leads (I, II, aVR, and aVF), precordial leads (V3-V6), and synthesized leads (syn-V4R-5R), decreased QRS axis and duration, and lower prevalence of fragmented QRS than those without LVRR. The ECG score using 3 selected parameters (QRS amplitude in aVR ≥675 µV; QRS duration <106 ms without fragmentation; and QRS axis <67°) was associated with the incidence of LVRR even after adjusting for optimized treatment. Conclusions: The standard 12-lead ECG parameters are sufficiently predictive of LVRR in NICM patients.

Old-Age Onset Progressive Cardiac Contractile Dysfunction in a Patient with Polycystic Kidney Disease Harboring a PKD1 Frameshift Mutation.

A 70-year-old man with dyspnea was admitted to our department and received standard therapy for recurrent heart failure. He was diagnosed with polycystic kidney disease (PKD) in his thirties and received hemodialysis for 4 years before undergoing renal transplantation at age 45. Although his left ventricular ejection fraction (LVEF) was preserved in his 50s, LVEF decreased progressively from 61% to 24%, while left ventricular diastolic dimension (LVDd) increased from 54 mm to 65 mm between 63 and 69 years of age. Right ventricular endomyocardial biopsy demonstrated myocardial disarray and interstitial fibrosis. Genetic analysis identified a heterozygous frameshift mutation in PKD1, which encodes polycystin-1, a major causative gene of PKD. We detected PKD1 protein expression in myocardial tissue by immunostaining. Recent epidemiological studies and animal models have clarified the pathological correlation between ventricular contractile dysfunction and PKD1 function. Here, we present a case of old-age onset progressive cardiac contractile dysfunction with a PKD1 gene mutation.

A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure.

BACKGROUND: Accurate prediction of both mortality and morbidity is of significant importance, but it is challenging in patients with severe heart failure. It is especially difficult to detect the optimal time for implanting mechanical circulatory support devices in such patients. We aimed to analyze the morphometric ultrastructure of nuclear chromatin in cardiomyocytes by developing an original clinical histopathological method. Using this method, we developed a biomarker to predict poor outcome in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: As a part of their diagnostic evaluation, 171 patients underwent endomyocardial biopsy (EMB). Of these, 63 patients diagnosed with DCM were included in this study. We used electron microscopic imaging of cardiomyocyte nuclei and an automated image analysis software program to assess whether it was possible to detect discontinuity of the nuclear periphery. Twelve months after EMB, all patients with a discontinuous nuclear periphery (Group A, n = 11) died from heart failure or underwent left ventricular assist device (VAD) implantation. In contrast, in patients with a continuous nuclear periphery (Group N, n = 52) only 7 patients (13%) underwent VAD implantation and there were no deaths (p<0.01). We then evaluated chromatin particle density (Nuc-CS) and chromatin thickness in the nuclear periphery (Per-CS) in Group N patients; these new parameters were able to identify patients with poor prognosis. CONCLUSIONS: We developed novel morphometric methods based on cardiomyocyte nuclear chromatin that may provide pivotal information for early prediction of poor prognosis in patients with DCM.

Usefulness of transient elastography for noninvasive and reliable estimation of right-sided filling pressure in heart failure.

Accurate noninvasive assessment of right atrial pressure (RAP) is important for volume management in patients with heart failure (HF). Transient elastography is a noninvasive and reliable method to assess liver stiffness (LS). We investigated the value of LS for evaluation of RAP in patients with HF without structural liver disease. We measured LS using transient elastography (Fibroscan) in 31 patients undergoing right-sided cardiac catheterization (test group). The relation between LS and RAP found in the test group was used to derive the best-fit model to predict RAP. The applicability of the model was then tested in a validation group of 49 additional patients. There was an excellent correlation between LS and RAP in the test group (r = 0.95, p <0.0001; RAP = -5.8 + 6.7 × ln [LS]). Natural log transformation (ln) of LS provided the regression equation to predict RAP. When the equation model derived from the test group was applied to the validation group, predicted RAP correlated excellently with actual RAP (r = 0.90, p <0.0001). The receiver operating characteristic curve analyses in the test group showed that LS favorably compared with echocardiography for detecting RAP >10 mm Hg (area under the curve 0.958 vs 0.800, respectively, p = 0.047). In the validation group, LS with a cut-off value of 10.6 kPa for identifying RAP >10 mm Hg had a higher sensitivity and accuracy (p = 0.046 and p = 0.049, respectively) than echocardiography. In conclusion, LS may offer an accurate noninvasive diagnostic method to assess RAP in patients with HF.

Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension.

BACKGROUND: Treatment with carvedilol is an established primary therapy for patients with heart failure (HF). However, its most common adverse effects, dizziness and hypotension, often discourage continuation or dosage increase. The aim of this study was to examine whether switching to bisoprolol from carvedilol would help to avoid adverse symptoms and signs related to carvedilol administration. METHODS AND SUBJECTS: Data were retrospectively collected from 23 patients with HF [age 57±18 years, left ventricular ejection fraction (LVEF) 33±15%] who could not increase the dosage of carvedilol because of dizziness or hypotension, defined as systolic blood pressure<90 mmHg. Before and immediately after, and 6 months after switching to bisoprolol, we examined symptoms, vital signs, laboratory data, and New York Heart Association functional class. Furthermore, left ventricular (LV) dimension and ejection fraction (EF) were evaluated in 19 patients using echocardiography. RESULTS: All 13 patients with dizziness (100%) and 9 of 16 with hypotension (56%) were relieved of adverse symptoms or signs. The mean dose of carvedilol before switching was 5.60±3.43 mg. Immediately after the switch, the mean dose of bisoprolol was 1.84±1.08 mg and then increased to 3.13±1.74 mg after 6 months (p<0.01). At 6-month follow-up examinations, LV function determined by LVEF was significantly improved, which was accompanied by increased exercise tolerance. CONCLUSION: Switching from carvedilol to bisoprolol may help with continuation of ß-blocker treatment as well as dosage increase in HF patients with adverse symptoms or signs, allowing them to reach the target dose.