Arrhythmias In Dilated Cardiomyopathy Research Articles

PO-03-221 BURDEN OF ARRHYTHMIAS AND CLINICAL OUTCOMES IN PATIENTS WITH DILATED CARDIOMYOPATHY ACCORDING TO LARGE DATASET

Dilated cardiomyopathy (DCM) is characterized by dilation & impaired systolic function of one or both ventricles. Although heart rhythm disorders are associated with DCM, description of their prevalence & clinical outcomes is limited in the literature. Aim of this study was to investigate the burden, basic characteristics, & clinical outcomes of arrhythmias in DCM. We queried the National Inpatient Sample between 2017-2020 for adult patients who were hospitalized with DCM. The primary outcome was inpatient mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, invasive mechanical ventilation, length of stay (LOS) & total hospital cost. Multivariable logistic, linear & Poisson regression analyses were used to estimate clinical outcomes. p-value < 0.05 was significant. There were 875,625 hospitalizations with DCM, of which 402,947 (46.1%) had arrhythmia of any type. Mean age was 64.2 yrs, 57.7% were Caucasian, 66.2% were male. The most prevalent arrhythmia was ventricular tachycardia (VT) 105,810 (12.08%), followed by paroxysmal atrial fibrillation (AFib) 104,330 (11.9%), permanent AFib 77824 (8.8%), persistent AFib 30,810 (3.5%), different degree of atrioventricular block (AVB) 26,644 (3.04%) with complete AVB being the most frequent (1.5%), & sick sinus syndrome 20220 (2.3%). Subgroup with arrhythmia vs without arrhythmia had HTN 6.3% vs 8.2%; PH 19.8% vs 15.5%; HF 89.0% vs 85.9%; HLD 53.3% vs 47.2%; CKD 45.5% vs 39.7%; COPD 28.3% vs 26.9%, respectively. During hospitalization, these subgroups had following complication rates: ACS 12.5% vs 14.1%; AKI 37.6% vs 31.8%; stroke 2.8% vs 3.1%, respectively. Subgroup with arrhythmia was associated with higher ICD (6.1% vs 2.0%), PPM (2.4% vs 0.2%), and LVAD (1.4% vs 0.6%) insertion rate. Subgroup with VT showed worse primary and secondary outcomes, while populations with AFib and AVB showed significant secondary outcomes (Table 1). Significant proportion of DCM patients is affected by arrhythmia (46%), where VT, AFib, AVB, & sick sinus syndrome being the most prevalent. Subgroup with arrhythmia is associated with HF, PH, HLD, CKD, COPD & with increased insertion rates of PPM, ICD, LVAD devices. Moreover, DCM population with different types of arrhythmias showed worse clinical outcomes & had higher resource utilization. This signifies the importance of early detection & treatment of rhythm disorders in DCM population. More research aimed at pathogenesis & long-term outcomes is needed.

Mid-wall striae fibrosis predicts heart failure admission, composite heart failure events, and life-threatening arrhythmias in dilated cardiomyopathy

Heart failure (HF) admission is a dominant contributor to morbidity and healthcare costs in dilated cardiomyopathy (DCM). Mid-wall striae (MWS) fibrosis by late gadolinium enhancement (LGE) imaging has been associated with elevated arrhythmia risk. However, its capacity to predict HF-specific outcomes is poorly defined. We investigated its role to predict HF admission and relevant secondary outcomes in a large cohort of DCM patients. 719 patients referred for LGE MRI assessment of DCM were enrolled and followed for clinical events. Standardized image analyses and interpretations were conducted inclusive of coding the presence and patterns of fibrosis observed by LGE imaging. The primary clinical outcome was hospital admission for decompensated HF. Secondary heart failure and arrhythmic composite endpoints were also studied. Median age was 57 (IQR 47–65) years and median LVEF 40% (IQR 29–47%). Any fibrosis was observed in 228 patients (32%) with MWS fibrosis pattern present in 178 (25%). At a median follow up of 1044 days, 104 (15%) patients experienced the primary outcome, and 127 (18%) the secondary outcome. MWS was associated with a 2.14-fold risk of the primary outcome, 2.15-fold risk of the secondary HF outcome, and 2.23-fold risk of the secondary arrhythmic outcome. Multivariable analysis adjusting for all relevant covariates, inclusive of LVEF, showed patients with MWS fibrosis to experience a 1.65-fold increased risk (95% CI 1.11–2.47) of HF admission and 1-year event rate of 12% versus 7% without this phenotypic marker. Similar findings were observed for the secondary outcomes. Patients with LVEF > 35% plus MWS fibrosis experienced similar event rates to those with LVEF ≤ 35%. MWS fibrosis is a powerful and independent predictor of clinical outcomes in patients with DCM, identifying patients with LVEF > 35% who experience similar event rates to those with LVEF below this conventionally employed high-risk phenotype threshold.

Enhancing risk stratification for life‐threatening ventricular arrhythmias in dilated cardiomyopathy: the peril and promise of precision medicine

Enhancing risk stratification for life‐threatening ventricular arrhythmias in dilated cardiomyopathy: the peril and promise of precision medicine

P1113Patchy localisation of late gadolinium enhancement associated with ventricular arrhythmia in dilated cardiomyopathy

Abstract Funding Acknowledgements None Introduction Myocardial fibrosis detected using late gadolinium enhancement(LGE) on cardiac magnetic resonance(CMR) imaging holds prognostic value in dilated cardiomyopathy(DCM). Recent reports have demonstrated the localisation of LGE to be promising predictors of ventricular arrhythmic (VA).Aim: To determine the localisation of LGE associated with high risk of VA in DCM patients. Methods: Retrospective review of consecutive DCM patients(n = 85) implanted with an implantable cardioverter defibrillator(ICD) at a single tertiary centre between 2011-2018. All patients with insufficient follow-up data, cardiac channelopathies, primary valvular pathology and congenital heart disease were excluded from analysis(n = 11). Details of VA occurrence were obtained from medical and pacing notes. VA was defined as VA causing haemodynamic compromise or appropriate device therapy (anti-tachycardia pacing/shock). Localisation of LGE was defined as midwall, patchy, subepicardial or transmural. Left ventricular ejection fraction(LVEF) &amp;lt;35% was defined as severely impaired function. Results:74 DCM patients implanted with an ICD were identified for analysis; LGE was observed in 18(60%) VA and 29(66%) non-VA patients(p = 0.6). There was no observed difference in mean age for patients with and without LGE (68 ± 10 vs. 65 ± 10 years,p = 0.07). A significant difference was seen between localisation and VA (p = 0.04), with patchy LGE demonstrating a higher arrhythmic risk(p = 0.005). There was no association between LVEF and LGE(p = 0.2) however, a significant difference was seen in LVEF and arrhythmic risk, with a more severely impaired LV function seen in patients without VA(p = 0.01). Conclusion:This study has demonstrated a patchy LGE localisation to be strongly associated with ventricular arrhythmia in DCM. Whilst this is a valuable tool in risk stratification, a prospective study with a larger population is required to confirm the validity of this finding. Moreover, an additional method will need to be considered to identify high risk patients without LGE. Ventricular Arrhythmia (n = 30) No Ventricular Arrhythmia (n = 44) P Value Male(%) 20(67%) 24(55%) p = 0.29 Age(Mean ± SD) 65 ± 12 65 ± 10 p = 0.36 LGE Midwall 10(56%) 24(83%) p = 0.04 Subepicardial 1(5.5%) 2(7%) p = 0.85 Transmural 1(5.5%) 2(7%) p = 0.85 Patchy 6(33%) 1(3%) p = 0.005 LVEF &amp;lt;35% 23(77%) 42(95%) p = 0.01

Predicting sustained ventricular arrhythmias in dilated cardiomyopathy: a meta-analysis and systematic review.

AimsPatients with non‐ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter‐defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM.Methods and resultsWe searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow‐up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74–1.00)], hypertension [HR 1.95; 95% CI (1.26–3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32–13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19–1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02–7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non‐sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin‐C (FLNC)] were associated with arrhythmic outcome in non‐pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high.ConclusionsIn patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non‐)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter‐defibrillator implantation.

Transcriptome signature of ventricular arrhythmia in dilated cardiomyopathy reveals increased fibrosis and activated TP53

AimsOne-third of DCM patients experience ventricular tachycardia (VT), but a clear biological basis for this has not been established. The purpose of this study was to identify transcriptome signatures and enriched pathways in the hearts of dilated cardiomyopathy (DCM) patients with VT. Methods and resultsWe used RNA-sequencing in explanted heart tissue from 49 samples: 19 DCM patients with VT, 16 DCM patients without VT, and 14 non-failing controls. We compared each DCM cohort to the controls and identified the genes that were differentially expressed in DCM patients with VT but not without VT. Differentially expressed genes were evaluated using pathway analysis, and pathways of interest were investigated by qRT-PCR validation, Western blot, and microscopy. There were 590 genes differentially expressed in DCM patients with VT that are not differentially expressed in patients without VT. These genes were enriched for genes in the TGFß1 and TP53 signaling pathways. Increased fibrosis and activated TP53 signaling was demonstrated in heart tissue of DCM patients with VT. ConclusionsOur study supports that distinct biological mechanisms distinguish ventricular arrhythmia in DCM patients.

Genetic arrhythmias complicating patients with dilated cardiomyopathy

Sudden cardiac death due to malignant arrhythmias is a common cause of death in dilated cardiomyopathy (DCM). Whether genetic variants increase the risk of arrhythmias in DCM is unknown. The purpose of this study was to investigate the genetic causes of arrhythmias in DCM patients. Whole-exome sequencing and high-depth targeted next-generation sequencing (142-gene panel) were used. Eight specific DCM pedigrees with arrhythmias and 2 separate cohorts of 1232 consecutive unrelated sporadic DCM patients from 3 medical centers (550 in the discovery cohort, 682 in the replication cohort) were analyzed; 470 (250 in the discovery cohort, 220 in the replication cohort) suffered from arrhythmias (DCM-A group) and 762 (300 in the discovery cohort, 462 in the replication cohort) did not (DCM-NA group). All identified causative variants were Sanger sequenced to eliminate false-positive results and then screened in 700 unrelated matched arrhythmia- and DCM-free healthy controls. We identified long QT syndrome (LQTS)-causative variants that independently cosegregated in 2 unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes (ion channelopathies) were identified in 4.9% (23/470) of sporadic DCM-A patients (4.0% in the discovery cohort, 5.9% in the replication cohort) but only 0.1% (1/762) of sporadic DCM-NA patients (P=2.16 × 10-9). These arrhythmia-related pathogenic variants included long QT syndrome, atrial fibrillation, sick sinus syndrome, cardiac conduction disease, and Brugada syndrome. Some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants. For DCM patients with explicit arrhythmias, arrhythmia-causative genetic screening may help to explain the etiology and decision-making.

Complexity of scar and ventricular arrhythmias in dilated cardiomyopathy of any etiology: Long-term data from the SCARFEAR (Cardiovascular Magnetic Resonance Predictors of Appropriate Implantable Cardioverter-Defibrillator Therapy Delivery) Registry.

Late gadolinium enhancement (LGE) assessed with cardiovascular magnetic resonance (CMR) correlates with ventricular arrhythmias and survival in patients with structural heart disease. Whether some LGE characteristics may specifically improve prediction of arrhythmic outcomes is unknown. We sought to evaluate scar characteristics assessed with CMR to predict implantable cardioverter-defibrillator (ICD) interventions in dilated cardiomyopathy of different etiology. 96 consecutive patients evaluated with CMR received an ICD. Biventricular volumes, ejection fraction, and myocardial LGE were evaluated. LGE was defined as "complex" (Cx-LGE) in presence of ≥1 of the following: ischemic pattern, involving ≥2 different coronary territories; epicardial pattern; global endocardial pattern; and presence of ≥2 different patterns. The primary endpoint was occurrence of any appropriate ICD intervention. A composite secondary endpoint of cardiovascular death, cardiac transplantation, or ventricular assist device implantation was also considered. During a median follow-up of 75 months, 30 and 25 patients reached the primary and secondary endpoints, respectively. Cx-LGE was correlated with a worse primary endpoint survival (log-rank P < 0.001). Cx-LGE and right ventricular end-diastolic volume were independently associated with the primary endpoint (HR: 3.22, 95% CI: 1.56-6.65, P = 0.002; and HR: 1.06, 95% CI: 1.00-1.12, P = 0.045, respectively), but not with the secondary endpoint. Cx-LGE identified at CMR imaging seems promising as an independent and specific prognostic factor of ventricular arrhythmias requiring ICD therapy in dilated cardiomyopathy of different etiologies.

P5856Identification of genetic etiology of malignant arrhythmia in dilated cardiomyopathy

P5856Identification of genetic etiology of malignant arrhythmia in dilated cardiomyopathy

Relationship of postcontrast myocardial T1 value and delayed enhancement to reduced cardiac function and serious arrhythmia in dilated cardiomyopathy with left ventricular ejection fraction less than 35.

Dilated cardiomyopathy (DCM) is often associated with progressive heart failure or ventricular arrhythmia. Look-Locker magnetic resonance imaging (MRI) allows quantitative evaluation of interstitial fibrosis by measuring the myocardial T1 value, and delayed enhancement (DE) MRI visualizes myocardial scar. To determine the relationship of postcontrast myocardial T1 value or DE to reduced cardiac function or sustained ventricular tachycardia (SVT) in DCM patients with a left ventricular ejection fraction (LVEF) <35%. We enrolled 41 patients with DCM. Correlations between the cardiac function parameters and postcontrast myocardial T1 value or extent of DE were evaluated. The relationship between SVT and the T1 values or extent of DE was assessed. The correlation between the extent of DE and the T1 value was also examined. The postcontrast myocardial T1 value was significantly correlated with the LVEF (P < 0.05; r = 0.31) and end-diastolic volume (P < 0.01; r = -0.40) in 40 patients with LVEF <35%. DE was not correlated with the cardiac function, but provided a high negative predictive value of 94.7% for SVT. No correlation was found between the myocardial T1 value and extent of DE. In DCM patients with LVEF <35%, the postcontrast myocardial T1 value correlated with the severity of cardiac dysfunction, and the absence of DE indicated the low risk of SVT. Both MRI parameters should be estimated because they may reflect discrete forms of myocardial damages in patients with DCM.

Arrhythmias in dilated cardiomyopathy.

Patients with dilated cardiomyopathies (DCM) face a significant burden of arrhythmias, including conduction defects such as atrioventricular block and interventricular delay in the form of left bundle branch block, resulting in altered electromechanical coupling that can exacerbate heart failure. Atrial fibrillation is common and carries an adverse prognosis. Ventricular arrhythmias and sudden cardiac death generally occur late in the disease course. Sustained monomorphic ventricular tachycardia accounts for most of the sustained ventricular arrhythmias in DCM. This article summarizes common forms of arrhythmias encountered in patients with DCM, and reviews the relevant electrophysiologic basis of these arrhythmias and their management.

Ion Channel Remodeling in Failing and Non-Failing Hearts of Inherited DCM Mouse Model -Usefulness of Running Wheel in Detection of Heart Failure-

Dilated cardiomyopathy (DCM) is a progressive disease often associated with heart failure (HF) and sudden death (SD). We have been studying cause and mechanism of SD/lethal arrhythmia in DCM using a mouse model with a mutation in cardiac troponin T (ΔK210), which displays cardiac dilation and shows frequent death with t1/2 of ∼70 days. In experiments with such mouse models with progressive heart diseases, it is necessary to assess severity of HF in living mice. To do so we measured voluntary exercise using a running wheel (r=6cm). Wheel-running activity was basically similar between wild type (WT) and DCM mice (17.1±5.7 vs 17.5±6.9 x 103 rounds/day (rpd)) until 2 months old. After then, however, some DCM mice died suddenly while keeping their running activity and others started to lose running activity and died. DCM mice were divided into two groups; mice with normal (>15000 rpd) and decreased running activity (<2000 rpd), and heart weight/body weight ratio (HW/BW) and lung weight/body weight ratio (LW/BW) were determined as indicatives of cardiac dilation and congestive HF, respectively. There was a significant negative correlation between running activity and LW/BW ratio, indicating that running wheel is a useful for detecting congestive HF in mouse model. These results suggest that some of the DCM mice die suddenly without HF, probably with lethal arrhythmia, whereas others develop severe HF and die. We carried out real-time PCR analysis for BNP and ion channels in two groups. The difference and similarity in expression levels of ion channels between two groups will be discussed.

Correlation of connexin43 expression and late ventricular potentials in nonischemic dilated cardiomyopathy.

Nonischemic dilated cardiomyopathy (DCM) is associated with a high risk of sudden cardiac death. Signal-averaged electrocardiography (SAECG) is a useful clinical tool for detecting late ventricular potentials (LP). Gap junction alterations have recently been shown to be involved in the pathogenesis of ventricular arrhythmias in DCM; however, the possible relationship between gap junctional connexin43 (C x 43) expression and SAECG has not yet been evaluated. In the present study 16 patients (47+/-13 years) with DCM who had undergone SAECG testing were evaluated. In each patient, the expression of C x 43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy and right ventricular biopsy specimens. The level of expression of C x 43 protein was defined as the proportion of tissue area occupied by C x 43 (percent tissue area) in each test area. The abundance and distribution of the C x 43 signal was assessed in relation to LP. Late ventricular potentials were positive in 5 patients (LP (+) group) and negative in 11 patients (LP (-) group). The incidence of sustained ventricular tachycardia in the LP (+) group was higher than that in the LP (-) group (80% vs 18%, p=0.04). The percent tissue area of C x 43 in the LP (+) group was significantly lower than that in the LP (-) group (p=0.02). Furthermore, C x 43 protein in the LP (+) group was distributed more heterogeneously than that in the LP (-) group (p=0.001). The heterogeneous expression of C x 43 protein may contribute to impaired ventricular conduction, which may be related to the LP detected on SAECG.

Repolarization abnormalities detected by magnetocardiography in patients with dilated cardiomyopathy and ventricular arrhythmias.

Abnormal repolarization is one of the acknowledged mechanisms leading to malignant ventricular arrhythmias. We used a novel magnetocardiographic technique to investigate the role of inhomogeneous repolarization in patients with nonischemic dilated cardiomyopathy prone to sustained ventricular arrhythmias. Forty-nine dilated cardiomyopathy patients were studied, 18 with a history of sustained ventricular tachycardia (n = 6) or ventricular fibrillation (n = 12) and 31 with no ventricular arrhythmias. The magnetocardiogram was registered and QT apex and QT end intervals were determined by a computer algorithm. Inhomogeneity of repolarization was characterized with indices describing QT apex and QT end dispersion, and T wave end duration. In addition, time-domain late fields of the QRS complex in magnetocardiography and QT dispersion in 12-lead ECG were determined. T wave end was longer in the arrhythmia group in patients with sinus rhythm (87 +/- 15 msec vs 73 +/- 12 msec; P = 0.005) and in those not having bundle branch block. Magnetocardiographic late fields of the QRS complex were not different between groups. QT apex and end dispersion on magnetocardiography or 12-lead ECG showed no difference. Prolongation of the end part of the T wave revealed by magnetocardiography is related to malignant ventricular arrhythmias in dilated cardiomyopathy. The results suggest that abnormal repolarization rather than delayed conduction underlies the arrhythmias in this disease.

Sudden death in dilated cardiomyopathy.

The purpose of this review is to examine the potential contribution of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss current treatment options. We performed a search of the MEDLINE database from 1985 to the present and the reference citations of selected articles pertaining to the prognostic significance, management, and pathophysiology of arrhythmias in DCM. A large proportion of patients with DCM die suddenly, most secondary to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The presence and severity of ventricular ectopy may predict risk for sudden death, but the role of electrophysiologic study and signal-averaged electrocardiography in further risk stratifying patients remains uncertain. Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme inhibitors improve overall mortality in congestive heart failure, and the use of direct angiotensin-receptor antagonists is currently being studied. In addition, beta-receptor antagonists appear to improve morbidity and may prove to improve mortality in heart failure as well. Other interventions still under investigation include amiodarone and the implantable cardioverter-defibrillator. The underlying pathophysiology of sudden death in DCM involves primarily ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of improving overall mortality, while further study on the roles for newer drugs and devices is ongoing.

Ventricular arrhythmias in dilated cardiomyopathy.

Although prognosis of dilated cardiomyopathy (DCM) has improved due to advances in diagnosis and therapy, still too many sudden cardiac deaths occur in DCM. Spontaneous ventricular ectopy is a very common finding in patients with DCM, but the prognostic significance of Holter monitoring remains controversial. Other noninvasive methods, e.g., late potentials and QT dispersion, have not yet contributed to the evaluation of prognosis for arrhythmogenic events in DCM. Programmed ventricular stimulation has been repeatedly used to stratify long-term prognosis, yet satisfactory data are still missing as many deaths occur in patients without inducible arrhythmias. Several prognostic studies are still in progress, and preliminary data for the use of ICDs already appear to be promising. In patients with poor left ventricular function and ICDs in situ, prognosis is determined by progression of heart failure. Heart transplantation may be the ultimate therapeutic instrument for end-stage heart failure patients. For patients with advanced DCM and increased risk for malignant arrhythmias who are unsuitable for orthotopic heart transplantation, the combined therapy with an ICD and dynamic cardiomyoplasty may be an alternative treatment.

Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark

Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p < 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 ± 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p < 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p < 0.001) and stroke work index (p < 0.001).

Relation of complex ventricular arrhythmias to presenting features and prognosis in dilated cardiomyopathy

To evaluate whether complex ventricular arrhythmias relate to presenting features and prognosis of dilated cardiomyopathy, 104 patients were studied from 1977 to 1987. At diagnosis, the 19 patients with complex ventricular arrhythmias (18%), as compared to the 85 patients without (82%), had a higher incidence of palpitation ( P < 0.01), severe dyspnea ( P < 0.001) and atrial fibrillation ( P < 0.01). They showed also higher mean right atrial pressures (10 ± 5 vs 6 ± 4 mm Hg, P < 0.001) and higher right ventricular end-diastolic pressures (11 ± 4 vs. 7 ± 4 mm Hg, P < 0.001) than patients without complex ventricular arrhythmias. Histologic samples were collected from the 32 patients (31%) studied since 1984 and semiquantitatively graded. The 11 patients with complex ventricular arrhythmias showed a higher frequency of severe interstitial fibrosis than the 21 patients without (64% vs. 24%, P < 0.05), but they were otherwise similar as to the frequency of marked myocellular hypertrophy, changes of myocardial regression, endocardial fibrosis, attenuation of myocytes, hyperplasia of smooth muscle cells and infiltration by inflammatory cells. During a follow-up of 3.8 ± 3.5 years, 35 patients (34%) died. Mortality was 58% (11 out of 19) in patients with complex ventricular arrhythmias and 28% (24 out of 85) in patients without ( P < 0.025). These results show that complex ventricular arrhythmias in dilated cardiomyopathy are associated with impairment of function of the right heart and severe interstitial fibrosis of the left ventricle, rather than with left ventricular dysfunction. Presence of complex ventricular arrhythmias also seems to identify those at high risk for death.

Dilated Cardiomyopathy

Dilated Cardiomyopathy

Analysis of ventricular arrhythmias in patients with dilated cardiomyopathy. Relationship between the effects of antiarrhythmic agents and severity of myocardial lesions.

In order to investigate the usefulness of antiarrhythmic drugs in patients with dilated cardiomyopathy (DCM), 42 patients with DCM were studied using 24 h ambulatory ECG monitoring, echocardiography and right ventricular endomyocardial biopsy. All 42 patients had ventricular arrhythmias with a Lown's classification of grade II or greater (grade IVb, 25; IVa, 7; III, 7; II, 3). The patients with grade IV arrhythmias tended to have greater dilating of the left ventricle and more pronounced interstitial myocardial fibrosis than patients with lower grades. Following procainamide and/or disopyramide treatment the severity of the ventricular arrhythmias improved in 12 (29%) of the 42 patients, did not change in 27 patients (64%), and deteriorated in 3 patients (7%). Treatment with aprindine or mexiletine was effective in 7 (50%) of the 14 patients who did not respond to procainamide and/or disopyramide. Although there were no significant differences in left ventricular dimension and contractility between patients in each group who did and did not respond to antiarrhythmic treatment, those who did respond had less interstitial myocardial fibrosis. Thus, in the procainamide and/or disopyramide treated group the percent interstitial fibrosis in responding vs nonresponding patients was 10.3 +/- 4.1% vs 18.7 +/- 8.3% (p less than 0.05) respectively, while in the group treated with aprindine or mexiletine these figures were 13.0 +/- 3.2% vs 26.1 +/- 7.9% (p less than 0.02), respectively. In conclusion, the effect of antiarrhythmic drugs in DCM was dependent on the severity of the pathological changes in the myocardium, and antiarrhythmic drugs should be appropriately used for the management of ventricular arrhythmias in DCM.