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Background: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. Methods: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. Results: Two hundred eighty-eight patients (41.0 +/- 14.5 years, 55.9% male, right ventricular ejection fraction 42.5 +/- 11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (PFunding Agencies|Leonie-Wild Foundation; Leyla Erkan Family Fund for ARVD Research; Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center; Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center; Dr. Francis P. Chiramonte Private Foundation; Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins; Bogle Foundation; Healing Hearts Foundation; Campanella Family; Patrick J. Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments; Fondation Leducq; National Center for Advancing Translational Sciences [UL1TR001079]; Philippa and Marvin Carsley cardiology research chair; Montreal Heart Institute Foundation; Georg und Bertha Schwyzer-Winiker Foundation; Baugarten Foundation; Swiss Heart Foundation [FF17019, FF21073]; Swiss National Science Foundation [160327]; Swedish Heart Lung Foundation [20200674]; Swedish state under the Avtal om lakarutbildning och forsknin (ALF)-agreement; Netherlands Cardiovascular Research Initiative; Dutch Heart Foundation [CVON201512/2018-30]

Background: Titin is a giant elastic protein that spans the half-sarcomere from Z-disk to M-band. It acts as a molecular spring and mechanosensor and has been linked to striated muscle disease. The pathways that govern titin-dependent cardiac growth and contribute to disease are diverse and difficult to dissect. Methods: To study titin deficiency versus dysfunction, the authors generated and compared striated muscle specific knockouts (KOs) with progressive postnatal loss of the complete titin protein by removing exon 2 (E2-KO) or an M-band truncation that eliminates proper sarcomeric integration, but retains all other functional domains (M-band exon 1/2 [M1/2]-KO). The authors evaluated cardiac function, cardiomyocyte mechanics, and the molecular basis of the phenotype. Results: Skeletal muscle atrophy with reduced strength, severe sarcomere disassembly, and lethality from 2 weeks of age were shared between the models. Cardiac phenotypes differed considerably: loss of titin leads to dilated cardiomyopathy with combined systolic and diastolic dysfunction—the absence of M-band titin to cardiac atrophy and preserved function. The elastic properties of M1/2-KO cardiomyocytes are maintained, while passive stiffness is reduced in the E2-KO. In both KOs, we find an increased stress response and increased expression of proteins linked to titin-based mechanotransduction (CryAB, ANKRD1, muscle LIM protein, FHLs, p42, Camk2d, p62, and Nbr1). Among them, FHL2 and the M-band signaling proteins p62 and Nbr1 are exclusively upregulated in the E2-KO, suggesting a role in the differential pathology of titin truncation versus deficiency of the full-length protein. The differential stress response is consistent with truncated titin contributing to the mechanical properties in M1/2-KOs, while low titin levels in E2-KOs lead to reduced titin-based stiffness and increased strain on the remaining titin molecules. Conclusions: Progressive depletion of titin leads to sarcomere disassembly and atrophy in striated muscle. In the complete knockout, remaining titin molecules experience increased strain, resulting in mechanically induced trophic signaling and eventually dilated cardiomyopathy. The truncated titin in M1/2-KO helps maintain the passive properties and thus reduces mechanically induced signaling. Together, these findings contribute to the molecular understanding of why titin mutations differentially affect cardiac growth and have implications for genotype-phenotype relations that support a personalized medicine approach to the diverse titinopathies.

Background: The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH). Methods: Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity. RV ejection fraction was assessed in 112 patients with PAH. Expression of nicotinic (α-7 nicotinic acetylcholine receptor) and muscarinic (muscarinic acetylcholine type 2 receptor) receptors, and acetylcholinesterase activity were evaluated in RV (n=11) and lungs (n=7) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls. In addition, we investigated the effects of PYR (40 mg/kg per day) in experimental PH. PH was induced in male rats by SU5416 (25 mg/kg subcutaneously) injection followed by 4 weeks of hypoxia. In a subgroup, sympathetic/parasympathetic modulation was assessed by power spectral analysis. At week 6, PH status was confirmed by echocardiography, and rats were randomly assigned to vehicle or treatment (both n=12). At the end of the study, echocardiography was repeated, with additional RV pressure-volume measurements, along with lung, RV histological, and protein analyses. Results: Patients with PAH with lower RV ejection fraction ( Conclusions: RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH.

A 64-year-old woman with a history of diabetes mellitus and hypertension presented to the emergency department with substernal chest pressure radiating to her back and left breast. Blood pressure was equal in both arms, and she was diagnosed with acute myocardial infarction. Despite adequate stent deployment resulting in excellent epicardial coronary artery flow, she developed confusion, hypotension, cool extremities, and an elevated serum lactate. The right-sided ECG in Figure 1 was obtained when she became hemodynamically unstable. Identify all the ECG abnormalities and the best management at this point. Figure 1. Right-sided ECG performed in a hemodynamically unstable patient. V3R through V6R are placed in their standard position along the right chest wall. Please turn the page to read the diagnosis. The right-sided ECG presented in Figure 1 shows atrial fibrillation with acute infero-posterior wall ST-segment–elevation myocardial infarction with right ventricular (RV) infarction. This ECG shows remarkable ST-segment elevations in the inferior and right-sided leads with reciprocal …

The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the extracellular matrix may help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis impairs cardiac function, and a growing body of experimental data suggests that fibrosis plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, the RV is exposed to a ≈5 times increased afterload, which makes these conditions excellent models for studying the impact of pressure overload on RV structure. With this review, we present clinical evidence of RV fibrosis in idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, explore the correlation between fibrosis and RV function, and discuss the clinical relevance of RV fibrosis in patients with PH. We postulate that RV fibrosis has a dual role in patients with pressure-overloaded RVs of idiopathic pulmonary arterial hypertension and chronic thromboembolic PH: as part of an adaptive response to prevent cardiomyocyte overstretch and to maintain RV shape for optimal function, and as part of a maladaptive response that increases diastolic stiffness, perturbs cardiomyocyte excitation-contraction coupling, and disrupts the coordination of myocardial contraction. Finally, we discuss potential novel therapeutic strategies and describe more sensitive techniques to quantify RV fibrosis, which may be used to clarify the causal relation between RV fibrosis and RV function in future research.

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran’s Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar’s test and Egger’s test. Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up. In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.

Background and Purpose:The diverse causes of right-sided heart failure (RHF) include, among others, primary cardiomyopathies with right ventricular (RV) involvement, RV ischemia and infarction, volume loading caused by cardiac lesions associated with congenital heart disease and valvular pathologies, and pressure loading resulting from pulmonic stenosis or pulmonary hypertension from a variety of causes, including left-sided heart disease. Progressive RV dysfunction in these disease states is associated with increased morbidity and mortality. The purpose of this scientific statement is to provide guidance on the assessment and management of RHF.Methods:The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through September 2017. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or reference to contemporary clinical practice recommendations.Results:Chronic RHF is associated with decreased exercise tolerance, poor functional capacity, decreased cardiac output and progressive end-organ damage (caused by a combination of end-organ venous congestion and underperfusion), and cachexia resulting from poor absorption of nutrients, as well as a systemic proinflammatory state. It is the principal cause of death in patients with pulmonary arterial hypertension. Similarly, acute RHF is associated with hemodynamic instability and is the primary cause of death in patients presenting with massive pulmonary embolism, RV myocardial infarction, and postcardiotomy shock associated with cardiac surgery. Functional assessment of the right side of the heart can be hindered by its complex geometry. Multiple hemodynamic and biochemical markers are associated with worsening RHF and can serve to guide clinical assessment and therapeutic decision making. Pharmacological and mechanical interventions targeting isolated acute and chronic RHF have not been well investigated. Specific therapies promoting stabilization and recovery of RV function are lacking.Conclusions:RHF is a complex syndrome including diverse causes, pathways, and pathological processes. In this scientific statement, we review the causes and epidemiology of RV dysfunction and the pathophysiology of acute and chronic RHF and provide guidance for the management of the associated conditions leading to and caused by RHF.

Although permanent cardiac pacing successfully restores a physiological heart rate in patients with atrioventricular block, it has become apparent in recent years that chronic right ventricular (RV) pacing can lead to serious adverse consequences such as adverse ventricular remodeling and heart failure. Algorithms that minimize RV pacing for patients with sinus node dysfunction or intermittent atrioventricular block are in widespread use to avoid the problems associated with chronic RV pacing. However, in patients with advanced atrioventricular block, high percentages of ventricular pacing are unavoidable. One approach to this problem is cardiac resynchronization therapy (CRT), in which a left ventricular lead in the coronary sinus paces simultaneously or near-simultaneously with an RV lead to allow more coordinated activation of the ventricles and avoid dyssynchrony. The BLOCK HF study (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block) showed that such an approach in patients with atrioventricular block and baseline left ventricular dysfunction (left ventricular ejection fraction [EF] ≤50% and New York Heart Association [NYHA] class I–III) led to better outcomes than RV pacing, including less adverse ventricular remodeling, a lower incidence of heart failure events, and better clinical composite scores.1 CRT has also proven to be valuable in patients with systolic heart failure without atrioventricular block but with evidence of conduction system disease manifested as a prolonged QRS duration, usually left bundle-branch block. Multiple trials …

Systemic sclerosis (SSc) describes a range of heterogeneous clinical disorders that are characterized broadly by increased inflammation and autoimmunity, which promote fibrosis in visceral organs and the pulmonary and systemic circulatory beds. The pattern of scleroderma (ie, skin thickening) categorizes patients further as limited cutaneous SSc (which includes the CREST [calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome) or diffuse cutaneous SSc. Involvement of the myocardium, pericardium, cardiac conduction system, or pulmonary vasculature is observed in up to 25% of affected patients but may contribute to the constellation of clinical findings accompanying either disease subtype.1 However, pulmonary arterial hypertension (PAH), which in this patient population is attributable to effacement of pulmonary arterioles primarily from severe hypertrophic and fibrotic remodeling, occurs more commonly in patients with limited cutaneous SSc.2 Article, see p 2413 There is important overlap between SSc and primary pulmonary vascular disease, including idiopathic PAH (iPAH). Hyperinflammation, dysregulated humoral autoimmunity, and platelet overactivation are common to both and in each case mediate endothelial dysfunction, fibrillar collagen deposition, and intimal thickening of pulmonary arterioles. Increased vascular reactive oxygen species accumulation and abnormalities to pathways that involve Wnt ligands, connective tissue growth factor, endothelin-1, and the nuclear receptor peroxisome proliferator-activated receptor-γ represent just a minority of pathogenetic mechanisms implicated in the development of SSc and the pulmonary vasculopathy of iPAH.3–6 This overlap is likely to account for elevated PAH prevalence in SSc that by some estimates reaches 12%, which is a substantially higher rate compared with other at-risk subgroups such as those with sickle cell anemia and HIV, of whom PAH affects 3% and 0.5% of patients, respectively.7 On the basis of similarities in vascular pathophenotype, it may also …

We thank Dr Murakami and his colleagues for their interest in our article.1 They express concern for the potential risk of patients on β-blockers with sepsis or pneumonia, and especially patients with preexisting asplenia, developing intractable hypoglycaemia and catecholamine-resistant hypotension. There is no evidence in the literature or any plausible mechanism suggestive of a direct link between β-blockade and such …

We read with great interest the article by Brida et al1 that described an approach to the management of patients with systemic right ventricle (SRV). The article was highly informative; however, we would like to discuss pharmacological therapy in patients with SRV. In the article, the authors stated that β-blockers may have a beneficial …

Background— This study sought to analyze a new approach to assess exercise-induced pulmonary artery systolic pressure (PASP) increase by means of stress Doppler echocardiography as a possible measure of right ventricular contractile reserve in patients with severe pulmonary hypertension and right heart failure. Methods and Results— In this prospective study, patients with invasively diagnosed pulmonary arterial hypertension or inoperable chronic thromboembolic pulmonary hypertension and impaired right ventricular pump function despite a stable targeted pulmonary arterial hypertension medication underwent a broad panel of noninvasive assessments, including stress echocardiography and cardiopulmonary exercise testing. On the basis of the assumption that exercise-induced PASP is a measure of right ventricular contractile reserve, patients were classified into 2 groups according to an exercise-induced PASP increase above or below the median. Patients were followed up for 3.0±1.8 years. Univariate and multivariate analyses were used for factors predicting survival. Of 124 patients, 66 were below the median exercise-induced PASP increase of 30 mm Hg (low PASP), and 58 patients were above the median (high PASP). These groups were not significantly different in terms of medication and resting hemodynamics. Low PASP was associated with a significantly lower 6-minute walking distance, peak o 2 per kilogram, and 1-, 3-, and 4-year survival rates (92%, 69%, and 48%, respectively, versus 96%, 92%, and 89%). In the multivariate Cox model analysis adjusted for age and sex, PASP increase during exercise and peak o 2 per kilogram remained independent prognostic markers (hazard ratio, 2.56 for peak o 2 per kilogram and 2.84 for PASP increase). Conclusions— Exercise-induced PASP increase is of high clinical and prognostic relevance in pulmonary hypertension patients and may indicate right ventricular contractile reserve. Stress Doppler echocardiography may be a useful tool for prognostic assessment in pulmonary hypertension patients.

Background— Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM. Methods and Results— We prospectively studied 250 consecutive DCM patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV ejection fraction ≤45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac transplantation. The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI], 3.35–10.37; P P P P =0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10–0.53; P =0.001). Conclusions— RVSD is a powerful, independent predictor of transplant-free survival and adverse heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV function is important in the evaluation and risk stratification of DCM patients.

We agree with Heidbuchel and colleagues that our findings do not clearly refute the concept of exercise-induced right ventricular (RV) damage because no prospective longitudinal study has been performed so far. However, our finding of marked RV remodeling without functional RV impairment or scarring challenges the notion of an exercise-induced arrhythmogenic right ventricular cardiomyopathy. First, we studied an exclusive cohort of world-class master endurance athletes with a training history of 29±8 years. Such athletes are not as easily available as ambitious recreational athletes, who would not demonstrate an extensive cardiac remodeling as our studied athletes. Our athletes demonstrated clear structural exercise-induced cardiac remodeling with a mild RV chamber size predominance of about 6% (left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio

Background: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. Methods: In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. Results: Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P =0.0003; ΔEes: -0.025 mm Hg/mL, P =0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P P =0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P 25 : -26.6 mL, P =0.0002; ΔEes: +0.034 mm Hg/mL, P =0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P Conclusions: Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. Clinical Trial Registration: URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844 . Unique identifier: NTR2844.

Background— Eisenmenger syndrome differs significantly from other types of pulmonary arterial hypertension in its physiology and prognosis. We sought to assess the relationship between the echocardiographic characteristics of patients with Eisenmenger syndrome and mortality. Methods and Results— Clinical and echocardiographic variables were assessed in 181 consecutive patients with Eisenmenger syndrome, excluding those with complex congenital heart disease. Patients' mean age was 39.1±12.8 years, 59 (32.6%) were male, 122 (67.4%) were in functional class III or higher, and 74 (40.9%) were on advanced therapies. Mean oxygen saturation at rest was 85.1±7.8%, and median B-type natriuretic peptide was 55.4 ng/L. Over a median follow-up of 16.4 months, 19 patients died; the strongest predictors of mortality were tricuspid annular plane systolic excursion and peak systolic velocity, myocardial performance (expressed as total isovolumic time and ratio of systolic to diastolic duration), and elevated central venous pressure (expressed as right atrial [RA] area, RA pressure, and ratio of RA to left atrial area), even after we accounted for advanced therapies. A composite score based on the strongest echocardiographic predictors of outcome, including 1 point for each of the following: tricuspid annular plane systolic excursion 2 , ratio of RA to left atrial area ≥1.5, was highly predictive of clinical outcome (area under the curve 0.90±0.01), with no improvement when B-type natriuretic peptide and resting saturations were added into the model. Conclusions— Echocardiographic parameters of right ventricular function and RA area predict mortality in Eisenmenger patients. A new composite echocardiographic score, described herewith, may be incorporated into the noninvasive, periodic assessment of these patients.

Background— It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. Methods and Results— Thirty-three healthy white competitive elite male master endurance athletes (age range, 30–60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m 2 ; P 2 ; P 2 ; P 2 ; P P =0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. Conclusions— Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned.

Background— Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease; however, determinants of RV anatomy have not been well studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease. Methods and Results— In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac magnetic resonance imaging was performed on 5098 participants. Right ventricular volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived with an allometric approach. The study sample (n=4123) was 61.5±10.1 years of age and 47.5% men. Older age was associated with lower RV mass (≈5% lower mass per decade), with larger age-related decrements in men than in women ( P P ≤0.01 for interaction). Overall, men had greater RV mass (≈8%) and larger RV volumes than women, but had lower RV ejection fraction (4% in absolute terms; P P ≤0.002), whereas Hispanics had higher RV mass ( P ≤0.02). When the derived normative equations were used, 7.3% (95% confidence interval, 6.5 to 8.1) met the criteria for RV hypertrophy, and 5.9% (95% confidence interval, 5.2 to 6.6) had RV dysfunction. Conclusion— Age, sex, and race are associated with significant differences in RV mass, RV volumes, and RV ejection fraction, potentially explaining distinct responses of the RV to cardiopulmonary disease.

Background— Tricuspid regurgitation in hypoplastic left heart syndrome has an impact on outcome, but its mechanisms remain unclear. Methods and Results— Real-time 3-dimensional echocardiography was performed in 35 patients with hypoplastic left heart syndrome (age, 1 month to 10 years; 10 after first-stage Norwood, 12 after superior cavopulmonary shunt, 13 after Fontan). From the 3-dimensional data set, we marked the annulus in systole and diastole. At mid systole, we marked the location of the papillary muscle tip and point of chordal attachment to the leaflet. We traced the surfaces of the tricuspid valve leaflets and measured the volume of leaflet prolapse, tethering, annular and septal leaflet areas, and papillary muscle position. Seventeen patients had moderate tricuspid regurgitation (prolapse, 7; tethered leaflets, 7) and 18 mild (prolapse, 0; tethered leaflets, 7). Multiple linear regression analysis revealed that moderate tricuspid regurgitation is associated with leaflet tethering and prolapse; that in hypoplastic left heart syndrome with tethered leaflets, the papillary muscle is displaced laterally and the tricuspid annulus is more planar; and that enlargement of the annulus at mid systole, small septal leaflet area, and age affect the degree of prolapse. Conclusion— In hypoplastic left heart syndrome, moderate tricuspid regurgitation may be associated with increasing age, geometrical changes of the annulus, leaflet prolapse, lateral papillary muscle displacement, and subsequent leaflet tethering, as well as a smaller septal leaflet.

Background— Off-pump CABG (OPCABG) results in better preservation of left ventricular function in the perioperative period than conventional on-pump CABG (ONCABG); however, evidence is conflicting as to the effect of OPCABG and ONCABG on right ventricular (RV) function, possibly because of the complexity involved in measuring this. Methods and Results— In a single-center randomized pilot study, 60 patients with normal left ventricular function undergoing CABG were randomly assigned to OPCABG or ONCABG. Patients underwent cardiac magnetic resonance imagine for assessment of RV function preoperatively, early postoperatively, and at 6 months after surgery. Fifty-one patients completed the first 2 scans, and 47 completed all 3 scans. Preoperative characteristics and RV function did not differ significantly between the 2 groups (mean±SD): RV stroke volume index was 49±10 mL/m 2 for OPCABG and 49±16 mL/m 2 for ONCABG. After surgery, RV stroke volume index fell to 36±7 mL/m 2 in the OPCABG group and 39±11 mL/m 2 in the ONCABG group, but this did not differ significantly between the 2 groups ( P =0.41). All markers of RV function recovered to preoperative levels by 6 months, with no long-term difference between the surgical techniques. Conclusions— RV function is impaired early after surgery but recovers by 6 months. The changes were similar in both the OPCABG and ONCABG groups.

Background— Patients after repair of tetralogy of Fallot (ToF) frequently have right ventricular (RV) dysfunction and prolonged QRS duration (QRSd) and thus could be candidates for cardiac resynchronization therapy. We aimed to assess the relationship between QRSd and the timing of RV wall motion, including the RV outflow tract (RVOT), in these patients. Methods and Results— Sixty-seven repaired ToF patients (median age, 34 years; interquartile range, 24 to 43 years) and 35 age-matched control subjects were studied by echocardiography and cardiovascular magnetic resonance (n=55 of 67 ToF patients). Time intervals of the RV cardiac cycle were measured from Doppler recordings. Long-axis M-mode recordings were acquired from the right ventricular (RV) free wall and RV outflow tract (RVOT), and the delay in onset of long-axis shortening was measured. ToF patients showed minor abnormalities of the RV cardiac cycle unrelated to QRSd. RV ejection time was prolonged and correspondingly filling time was reduced compared with control subjects (22.3±2.6 versus 20.0±2.9 s/min, P P P =NS). QRSd correlated with the delay in RV free wall motion ( r =0.55, P r =0.82, P r =−0.46, P =0.004; r =0.33, P =0.01). Conclusions— QRSd in postoperative ToF patients reflects mainly abnormalities of the RVOT rather than the RV body itself. Thus, prevention and treatment of mechanical asynchrony and malignant arrhythmia should focus on the RV infundibulum. Indications for cardiac resynchronization therapy after ToF repair warrant further investigation.

We thank Dr Guazzi for his interest in and insightful comments about our study of right ventricular (RV) dysfunction in heart failure (HF) with preserved ejection fraction.1 We agree that tricuspid annular plane systolic excursion (TAPSE), like any method of cardiac shortening (LV ejection fraction, RV ejection fraction, etc), is load dependent and influenced by RV afterload, a parameter related to but inadequately reflected by pulmonary artery systolic pressure (PASP). To address these limitations, we adjusted all analyses of the prognostic implications of RV dysfunction (by TAPSE …

I read with interest the article by Mohammed and coworkers1 on the prevalence and prognostic significance of right ventricular (RV) dysfunction in a large set of patients with heart failure with preserved ejection fraction. RV function was assessed by tricuspid annular systolic peak excursion (TAPSE) in 500 of 562 patients and by semiquantitative assessment in the whole population. Interestingly, patients with either mild or moderate to severe RV dysfunction by semiquantitative assessment compared with no RV dysfunction …

Background— The effect of a mutation in the bone morphogenetic protein receptor 2 ( BMPR2 ) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension is unknown. Therefore, we investigated RV function in patients who have pulmonary arterial hypertension with and without the BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular tissue. Methods and Results— In total, 95 patients with idiopathic or familial pulmonary arterial hypertension were genetically screened for the presence of a BMPR2 mutation: 28 patients had a BMPR2 mutation, and 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization and cardiac MRI. Despite a similar mean pulmonary artery pressure (noncarriers 54±15 versus mutation carriers 55±9 mm Hg) and pulmonary vascular resistance (755 [483–1043] versus 931 [624–1311] dynes·s −1 ·cm −5 ), mutation carriers presented with a more severely compromised RV function (RV ejection fraction: 37.6±12.8% versus 29.0±9%: P −1 ·m −2 ). Differences continued to exist after treatment. To investigate the role of transforming growth factor β and bone morphogenetic protein receptor II signaling, human RV and left ventricular tissue were studied in controls (n=6), mutation carriers (n=5), and noncarriers (n=11). However, transforming growth factor β and bone morphogenetic protein receptor II signaling, and hypertrophy, apoptosis, fibrosis, capillary density, inflammation, and cardiac metabolism, as well, were similar between mutation carriers and noncarriers. Conclusions— Despite a similar afterload, RV function is more severely affected in mutation carriers than in noncarriers. However, these differences cannot be explained by a differential transforming growth factor β, bone morphogenetic protein receptor II signaling, or cardiac adaptation.

Background: Decreased right ventricular (RV) ejection fraction (RVEF) portends poor prognosis in patients with ischemic cardiomyopathy, and previous studies have suggested an association between mitral regurgitation (MR) and RVEF. We sought to evaluate this association and whether mitral valve repair or replacement affects the relationship between RV function and mortality. Methods: We included 588 patients (mean age, 63±11 years; 75% male) with ischemic cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and 2008. Baseline characteristics, left ventricular ejection fraction, MR severity, treatment modality, scar burden, and RVEF were assessed. Multivariable linear regression and Cox proportional hazards models were used to assess the association between MR and RVEF and between RVEF and mortality, respectively. Results: After adjustment for age, sex, left ventricular ejection fraction, right bundle-branch block, and RV scar, MR severity was found to be associated independently with RVEF. There were a total of 240 deaths during a median follow-up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF was associated with a 17% increased risk of death ( P =0.008). Although decreasing RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio, 1.28; 95% confidence interval, 1.12–1.47; P P for interaction=0.046). ConclusionS: MR severity was found to be an independent predictor of RVEF, as were right bundle-branch block, left ventricular ejection fraction, and the presence of RV scar. Decreasing RVEF is associated with increased mortality in patients with ischemic cardiomyopathy; however, this association may be mitigated in patients who undergo mitral valve repair or replacement.

Background— Gaps of sufficient cross-sectional dimensions within linear radiofrequency (RF) lesions may allow conduction through the lesion. The purpose of this study was to examine the effects of different gap geometries on conduction through discontinuous RF lesions. Methods and Results— Radiofrequency lesions were created in isolated, perfused rabbit right ventricular (RV) free wall preparations to produce gaps with 3 different lesion geometries: straight, bifurcated, and angled (n=10 each group). Angled preparations contained 2 right angles within the conduction path. Optical mapping was used to assess bidirectional conduction through the myocardium before and after gap formation during pacing at 1000-, 400-, and 200-ms cycle lengths. Histological analysis was performed on each preparation after optical mapping. After lesion formation, 9 of 10 straight gap preparations and 1 of 10 angled gap preparations demonstrated bidirectional conduction ( P P Conclusions— Conduction through discontinuities in RF lesions is associated with gap geometry. Complex gap geometry may allow for unidirectional and/or rate-dependent block. Gaps within RF lesions are susceptible to pharmacological blockade.

Right heart size and function at baseline and follow-up are important predictors of outcome in pulmonary arterial hypertension (PAH). The traditional imaging indicators of right heart health include metrics of right ventricular (RV) systolic function under resting conditions. Transthoracic echocardiography is commonly used; RV size and function are often qualitatively described and may be quantifiable as well. Cardiac MRI is the "standard of reference" for RV morphology, whereas nuclear imaging techniques were used historically and have been employed more recently to measure RV metabolism. These techniques vary in technologic complexity, necessary equipment, and required expertise, yet all generally focus on systolic function of the RV at rest.

Background— Current evaluation of pulmonary hypertension (PH) in children involves measurement of pulmonary vascular resistance (PVR); however, PVR neglects important pulsatile components. Pulmonary artery (PA) input impedance and ventricular power (VP) include mean and pulsatile effects and have shown promise as alternative measures of vascular function. Here we report the utility of pulsed-wave (PW) Doppler-measured instantaneous flow and pressure measurements for estimation of input impedance and VP and use this method to develop a novel parameter: reactivity in compliance. Methods and Results— An in vitro model of the general pulmonary vasculature was used to obtain impedance and VP, measured by PW Doppler and a reference flow meter. The method was then tested in a preliminary clinical study in subjects with normal PA hemodynamics (n=4) and patients with PH undergoing reactivity evaluation (8 patients; 23 data points). In vitro results showed good agreement between the impedance spectra computed from both flow-measurement methods. Excellent correlation was seen in vitro between actual resistance and the zero-frequency (Z o ) impedance value ( r 2 =0.984). Excellent agreement was also found between Z o and PVR in the clinical measurements ( y =1.075 x +0.73; r =0.993). Furthermore, total VP and VP/cardiac output increased significantly with hypertension (128.73 to 365.91 mW and 2.42 to 6.69 mW · mL −1 · s −1 , respectively). The first-harmonic value of impedance (Z 1 ) was used as a measure of compliance reactivity; older patients exhibited markedly less compliance reactivity than did younger patients. Conclusions— Input impedance and VP calculated from Doppler measurements and a single-catheter pressure measurement provide comprehensive characterization of PH and reactivity.

Background— Phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil) are a novel, orally active approach to the treatment of pulmonary arterial hypertension. The role of natriuretic peptides in the response to sildenafil was examined in mice lacking NPR-A, a guanylyl cyclase-linked natriuretic peptide receptor, in which pulmonary hypertension was induced by hypoxia. Methods and Results— Mice homozygous for NPR-A ( NPR-A +/+ ) and null mutants ( NPR-A −/− ) were studied. Sildenafil inhibited the pressor response to acute hypoxia in the isolated perfused lungs of both genotypes. This effect was greater in the presence of atrial natriuretic peptide in the perfusate in NPR-A +/+ mice but not NPR-A −/− animals. In vivo, NPR-A mutants had higher basal right ventricular (RV) systolic pressures (RVSPs) than did NPR-A +/+ mice, and this was not affected by 3 weeks of treatment with sildenafil (25 mg · kg −1 · d −1 ). Both genotypes exhibited a rise in RVSP and RV weight with chronic hypoxia (10% O 2 for 21 days); RVSP and RV weight were reduced by continuous sildenafil administration in NPR-A +/+ mice, but only RVSP showed evidence of a response to the drug in NPR-A −/− mice. The effect of sildenafil on hypoxia-induced pulmonary vascular muscularization and cyclic GMP levels was also blunted in NPR-A −/− mice. Conclusions— The natriuretic peptide pathway influences the response to PDE5 inhibition in hypoxia-induced pulmonary hypertension, particularly its effects on RV hypertrophy and vascular remodeling.

Background This study investigated the effect of the phosphodiesterase 5 inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and mice. Methods and Results In a randomized, double-blind study, sildenafil 100 mg or placebo was given orally to 10 healthy volunteers 1 hour before breathing 11% O 2 for 30 minutes. Pulmonary artery pressure (PAP) was measured with an indwelling right heart catheter. The acute 56% increase in mean PAP produced by hypoxia during placebo treatment (mean PAP [mean±SD mm Hg]: normoxia 16.0±2.1 versus hypoxia 25.0±4.8) was almost abolished by sildenafil (normoxia 16.0±2.1 versus hypoxia 18.0±3.6), with no significant effect on systemic blood pressure. In the isolated perfused lung of wild-type and endothelial nitric oxide synthase (eNOS)-deficient mice, sildenafil markedly blunted acute hypoxic pulmonary vasoconstriction. Wild-type mice dosed orally with the drug (25 mg · kg −1 · d −1 ) throughout 3 weeks of exposure to hypoxia (10% O 2 ) exhibited a significant reduction in right ventricular systolic pressure (placebo versus sildenafil: 43.3±9.9 versus 29.9±9.7 mm Hg, P Conclusions Sildenafil attenuates hypoxia-induced pulmonary hypertension in humans and mice and offers a novel approach to the treatment of this condition. The eNOS-NO-cGMP pathway contributes to the response to sildenafil, but other biochemical sources of cGMP also play a role. Sildenafil has beneficial pulmonary hemodynamic effects even when eNOS activity is impaired.

Background —We previously reported that chronic endothelin (ET) receptor blockade ameliorated the survival rate and cardiac hemodynamics in rats with chronic heart failure (CHF) due to myocardial infarction. However, it remains unclear whether ET-1 is involved in the pathophysiology of cardiomyopathy, which is one of the major causes of CHF. Accordingly, we investigated the production of ET-1 in the heart and the effect of chronic ET A receptor blockade on survival rate and cardiac function in the Bio 14.6 hamster, which is an idiopathic model of CHF caused by cardiomyopathy. Methods and Results —We used 52-week-old Bio 14.6 cardiomyopathic hamsters and age-matched F1b normal hamsters. The expression of preproET-1 mRNA and the ET-1 level in the hearts were markedly higher in the cardiomyopathic hamsters than in the normal hamsters. The cardiomyopathic hamsters showed severe CHF, illustrated by lower left ventricular (LV) +dP/dt/P max and right ventricular (RV) +dP/dt/P max and by higher LV end-diastolic pressure (EDP), RVEDP, and central venous pressure compared with the normal hamsters. Long-term (9 weeks) treatment with an ET A antagonist (TA-0201, 1.3 mg · kg −1 · d −1 ) markedly increased survival of cardiomyopathic hamsters (untreated, 16%; TA-0201–treated, 65.2%; P max and RV +dP/dt/P max were significantly higher and LVEDP and RVEDP were lower in the TA-0201–treated group than in the untreated group, suggesting that chronic TA-0201 treatment effectively prevented deterioration of cardiac dysfunction. Conclusions —In the cardiomyopathic hamsters with CHF, the production of ET-1 in the heart was markedly increased, and chronic ET A receptor blockade greatly ameliorated survival and cardiac dysfunction. These results suggest that ET-1 plays an important role in the deterioration of CHF caused by cardiomyopathy, and ET A antagonists may exert therapeutic effects in CHF due to cardiomyopathy.

Background —Accurate quantitative evaluation of right ventricular (RV) function has been limited by its complex structural geometry. Although embryological and anatomic observations suggest that the RV is composed of 2 distinct components, the RV sinus and infundibulum, most studies on RV dimensions and function viewed it as a single chamber. This study was designed to determine the volumes, relative contribution to global systolic function, and temporal course of contraction and relaxation of the RV sinus and infundibulum. Methods and Results —Thirty-one individuals without heart disease (aged 1 month to 17 years, 16 boys and 15 girls) participated in this study. Instantaneous area over time, its derivatives, and the temporal course of contraction and relaxation were studied by acoustic quantification echocardiography and phonocardiography in 20 individuals. Global and regional RV volumes and ejection fraction were determined by cine MRI in 11 individuals. The RV sinus made up 81±6% of the combined RV end-diastolic volume and 87±4% of the combined stroke volume. The infundibulum accounted for the remaining 19±6% and 13±4%, respectively ( P P P P P ≤0.01), indicating a peristalsis-like pattern of contraction and relaxation. Conclusions —The results of this study demonstrate significant regional differences between the sinus and infundibulum components of the RV with regard to contribution to stroke volume, extent of fiber shortening, and sequence of mechanical activation. These data from normal individuals can be used in future research on RV function in pathological conditions.

Background —Left ventricular (LV) effects on right ventricular (RV) function are well known. Less is understood about the effect of the RV on systemic LV mechanics. To determine this interaction, we compared systemic LVs with and without an RV mechanically coupled to them. Methods and Results —MR myocardial tagging was used to examine 18 subjects with systemic LVs: 10 with functional single LVs (SLV) and 8 normal subjects (NL). Tracking the systolic motion of the intersecting stripes were used to determine regional twist and radial motion. Finite strain analysis was applied to derive principal strains at the atrioventricular valve (AVV) and apical short-axis levels and in 4 anatomic wall regions. Similar E 1 (circumferential shortening) strain and heterogeneity of strain were noted between SLV and NL except in the septal wall. At the septal wall, NL displayed greater absolute strain (AVV=−0.16±0.02, apex=−0.17±0.02) and less heterogeneity of strain than SLV (AVV=−0.12±0.02, apex=−0.13±0.02). Similar E 2 (wall thickening) strain and heterogeneity of strain were also noted between SLV and NL except again at the septal wall. At the septal wall, SLV displayed greater absolute E 2 strain (AVV=0.17±0.08, apex=0.19±0.09) and less heterogeneity of strain than NL (AVV=0.07±0.07, apex=0.05±0.05). SLV twisted significantly less counterclockwise than NL in 6 of 8 wall regions and actually twisted clockwise at the AVV lateral wall. Although there was no significant difference between groups in radial wall motion, the septal and inferior walls of SLV demonstrated significantly less radial motion compared with other SLV walls. Conclusions —A major influence of the RV on systemic LV strain and radial motion occurs in the septal wall, whereas absence of the RV causes marked differences in LV twist. These findings may yield clues to the long-term functioning of the SLV and be useful in determining strategies for RV augmentation of LV function.

Background Ventricular tachycardia originating in the right ventricle may arise in the presence or absence of structural heart disease. The two main causes of right ventricular tachycardia are arrhythmogenic right ventricular dysplasia (ARVD) and idiopathic right ventricular tachycardia (IRVT) originating from the outflow tract. This study was carried out to determine whether body-surface QRST integral mapping can differentiate patients with ARVD from patients with IRVT. Methods and Results Body-surface QRST integral maps were obtained during sinus rhythm in 8 patients with ARVD, 8 patients with IRVT, and 27 healthy control subjects. QRST integral maps were analyzed both visually and mathematically. All control subjects had a normal dipolar QRST integral map. In all patients with ARVD, a specific dipolar QRST integral map with an abnormally large negative area covering the entire inferior and right anterior thorax was recorded. In 6 of 8 patients with IRVT, a normal map pattern was found, whereas the remaining 2 patients showed an abnormally large negative area on the right anterior thorax. Conclusions Patients with ARVD display a specific abnormal QRST integral map that may be related to delayed repolarization in the structurally abnormal right ventricle. The majority of patients with IRVT demonstrate a normal QRST integral map. A slightly abnormal QRST integral map was noted in 2 of 8 patients with IRVT, which may be related to minor structural abnormalities, undetectable by the present routine diagnostic techniques. These preliminary results indicate that body-surface QRST integral mapping may become an important diagnostic tool to differentiate patients with ARVD from those with IRVT.

Background The contractile dysfunction observed in end-stage myocardial hypertrophy has at its base an abnormality in myocyte function. However, whether depressed contractile function is related to an alteration in contractile protein function is presently unknown. Methods and Results Contractile force, tension, and calcium responsiveness were measured in single-skinned myocytes isolated from rats with right ventricular hypertrophy (RVH) and control rats. RVH was induced by pulmonary artery constriction for 36 weeks and was associated with significant myocyte hypertrophy. Myocytes were attached to micropipettes that extended from a force transducer and motor. Isometric force was measured over a wide range of calcium concentrations at two sarcomere lengths (SLs). Maximal force was increased in the RVH group: 1.20±0.10 versus 1.62±0.13 mg at SL=2.0 μm and 1.33±0.10 versus 1.84±0.15 mg at SL=2.3 μm ( P 2 at SL=2.0 μm and 27.4±1.78 versus 41.8±3.19 mN/mm 2 at SL=2.3 μm ( P P P =.04) but not at SL=2.3 μm (3.8±0.2 versus 3.6±0.2, P =NS). Conclusions These results suggest that the depressed cardiac function of end-stage myocardial hypertrophy may be due, in part, to altered contractile protein function.

Background— Left ventricular assist devices (LVADs) provide better outcome than biventricular devices, but it is a challenge to predict the impact of LV mechanical unloading on postoperative right ventricular (RV) function preoperatively. We assessed the load dependency in RV performance before and after LVAD implantation aiming to improve preoperative decision making. Methods and Results— Laboratory, echocardiography, and right heart catheterization data collected from 205 patients before LVAD implantation were tested for relationship with postoperative RV function. Comparing patients with different time-course of RV function after LVAD implantation, we found significant differences ( P P RV−RA ), tricuspid regurgitation velocity-time integral, and pulmonary arterial pressure between patients with and without postoperative RV failure. High predictive values for postoperative RV failure were found for end-diastolic short-/long-axis ratio ≥0.6, tricuspid annulus peak systolic velocity P RV−RA 2 and pulmonary arterial pressure P RV−RA ≥35 mm Hg showed high predictive values for postoperative freedom from RV failure. The RV load adaptation index seemed particularly predictive for RV function after LVAD implantation. Conclusions— RV geometry and velocity of contraction before LVAD implantation become more predictive for postoperative RV function and can improve decision making before VAD implantation if preoperative RV pressure load and tricuspid regurgitation are also considered.

The heart of the athlete has intrigued cardiologists since the original description of increased cardiac dimensions in elite Nordic skiers more than a century ago.1 Athletes exhibit structural and electric cardiac abnormalities that mimic findings associated with cardiovascular disease.2 Some early observers regarded the heart of a conditioned athlete as weakened by strenuous training and thereby subject to progressive deterioration in function.3 Structural findings include chamber enlargement and ventricular hypertrophy.2,3 Electric abnormalities include increased QRS voltage, abnormal Q waves, and T-wave inversions.2,3 Currently, the athlete’s heart is regarded as a benign increase in cardiac mass with circulatory and morphological alterations in response to athletic training.2,3 Contemporary evidence supports the notion that this represents adaptive physiology, not preclinical disease.2,3 Despite considerable advances in diagnostic tests, significant challenges remain in differentiating the athlete’s heart from some types of cardiac disease.2–4 ECG and morphological changes found in athletes can mimic findings of hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC), and other cardiovascular diseases.2–4 The absence of a definitive diagnostic test or gold standard for many cardiovascular commonly results in diagnostic uncertainty.2–4 Article see p 1783 This overlap of normal and abnormal findings has represented a clinical challenge because diagnostic criteria lacked sufficient sensitivity and specificity to reliably distinguish physiological enlargement of the athlete’s RV from ARVC.5 The importance of this distinction is underscored by the fact that in the United States, ARVC is responsible for 4% of cases of athletic sudden deaths.2 Sudden deaths are attributed to ARVC in 22% of athletes in the Veneto region of Italy.2 Because of the recognized shortcomings of the 1994 International Task Force Criteria for the diagnosis …

Background— Regular, intensive exercise results in physiological biventricular cardiac adaptation. Ethnicity is an established determinant of left ventricular remodeling; black athletes (BAs) exhibit more profound LV hypertrophy than white athletes (WAs). Right ventricular (RV) remodeling has not been characterized in BAs, although the issue is pertinent because BAs commonly exhibit ECG anomalies that resemble arrhythmogenic RV cardiomyopathy. Methods and Results— Between 2006 and 2012, 300 consecutive BAs (n=243 males) from 25 sporting disciplines were evaluated by use of ECG and echocardiography. Results were compared with 375 WAs and 153 sedentary control subjects (n=69 blacks). There were no ethnic differences between RV parameters in control subjects. Both BAs and WAs exhibited greater RV dimensions than control subjects. RV dimensions were marginally smaller in BAs than in WAs (proximal outflow tract, 30.9±5.5 versus 32.8±5.3 mm, P P P P =0.005). Further investigation did not diagnose arrhythmogenic RV cardiomyopathy in any athlete. Conclusions— Physiological RV enlargement is commonly observed in both black and white athletes. The impact of ethnicity is minimal, which obviates the need for race-specific RV reference values. However, in the context of frequent ECG repolarization anomalies in BAs, the potential for erroneous diagnosis of arrhythmogenic RV cardiomyopathy is considerably greater in this ethnic group.

Background Right ventricular (RV) performance appears to be important in patients with severe heart failure. Although clinical assessments of RV function previously have been limited to load-dependent ejection phase indices, a new method has been developed using the relatively load-insensitive concepts of pressure-volume relations with automated echocardiographic measures of RV cross-sectional area as a surrogate for volume. Methods and Results Sixteen patients with New York Heart Association functional class IV heart failure and group mean left ventricular ejection fraction of 20±5% were studied. RV pressure-area loops were recorded on-line from echocardiographic measures of RV area and high-fidelity pressure during transient inferior vena caval balloon occlusions. RV contractile reserve was assessed as its functional response to an increase in dobutamine from 5.7±4.1 to 13.1±4.7 μg/kg per minute. Complete data sets were available in 13 patients. Group mean RV end-systolic elastance (E'es) and maximal elastance (E'max) increased with augmented dobutamine infusion (2.9±1.5 to 5.5±3.3 mm Hg/cm 2 and 3.3±1.6 to 6.4±3.9 mm Hg/cm 2 , respectively; P P Conclusions RV performance can be assessed by pressure-area relations in patients with heart failure. RV contractile reserve in response to increases in dobutamine was associated with a good short-term outcome and may be of prognostic value in patients with severe heart failure.

Background Ventricular arrhythmias after repair of congenital heart defects are a common finding and possibly contribute to sudden death in these patients. Optimal antiarrhythmic management has not yet been defined. Methods and Results The study population consisted of 16 patients in whom ventricular arrhythmias occurred 11 to 42 years after complete surgical repair of congenital heart defects. Fifteen patients had a history of symptomatic sustained or nonsustained ventricular tachycardia, and 1 had frequent nonsustained ventricular tachycardia. The diagnostic mapping procedure to identify the origin of the arrhythmia included pace mapping during sinus rhythm, activation mapping, and pacing interventions during ventricular tachycardia. Catheter ablation was carried out by means of radiofrequency energy in the temperature-controlled mode. The follow-up period was 6 to 33 months (mean, 16 months). A right ventricular origin of the tachycardia in the surgically corrected area could be determined in all patients. Catheter ablation was carried out without complications. Immediate noninducibility was achieved in 15 of the 16 patients. One patient in whom the tachycardia was again inducible at repeat stimulation 1 week later was successfully treated with amiodarone. Eleven patients were taken off antiarrhythmic drugs. During follow-up, none of them had a recurrence of the tachycardia that had been ablated. Conclusions In patients with symptomatic or frequent ventricular tachycardia late after complete surgical repair of congenital heart defects, catheter ablation by means of radiofrequency energy is feasible and safe and thus might be taken into consideration for these patients. Short-term follow-up results are promising.

Background Electron-beam computed tomography (CT) may be useful for detecting myocardial fat infiltration and diagnosing arrhythmogenic right ventricular dysplasia (ARVD). There are several characteristic electron-beam CT findings of ARVD. However, the incidence, their relation to electrophysiological abnormalities, and the usefulness of electron-beam CT for evaluating left ventricular involvement are unknown. This study aimed to clarify these issues. Methods and Results Electron-beam CT was performed in 14 patients with ARVD (ARVD group), 16 age- and sex-matched patients with right ventricular enlargement and/or dysfunction without ARVD (RV enlargement group), and 13 control subjects (control group). The incidences of abnormal electron-beam CT findings in the three groups were examined. Furthermore, we examined the endocardial fat–infiltrated areas detected by electron-beam CT (CT-A) and electrophysiologically abnormal areas detected in the mapping study (EPS-A) and compared the relationship between them in the ARVD group. (1) The frequencies of abundant epicardial adipose tissue, low-attenuation trabeculations, scalloping of the right ventricular free wall, and intramyocardial fat deposits were 86%, 71%, 79%, and 50%, respectively, in the ARVD group, whereas these findings were not observed in the RV enlargement and control groups. (2) Three ARVD patients (21%) had adipose tissue involvement of the left ventricle. (3) The relationship between CT-A and EPS-A was as follows: CT-A>EPS-A, 71%; CT-A=EPS-A, 14%; and EPS-A only, 14%. Conclusions Characteristic electron-beam CT findings are frequently observed only in patients with ARVD. Electron-beam CT is useful for evaluating for left ventricular involvement and can estimate EPS-A.