RESUMEN

BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive treatment of patients with refractory angina. The immediate hemodynamic effects of EECP are similar to intra-aortic balloon pump counterpulsation, but EECP's effects on standard blood pressure measurements during and after treatment are unknown. METHODS: We evaluated systolic blood pressure (SBP) and diastolic blood pressure (DBP) for 108 consecutive patients undergoing EECP. Baseline SBP, DBP, and heart rate were compared for each patient before and after each EECP session, at the end of the course of EECP, and 6 weeks after the final EECP session. RESULTS: One hundred eight patients (mean age 66.4 +/- 11.2 years, 81% male) completed 36.5 +/- 5.1 EECP sessions per patient. Overall, based on 3,586 individual readings, EECP resulted in a decrease in mean SBP of 1.1 +/- 15.3 mm Hg at the end of each EECP session (P < .001), 6.4 +/- 18.2 mm Hg at the end the course of EECP (P < .001), and 3.7 +/- 17.8 mm Hg 6 weeks after the final EECP session (P = .07), with no significant change in DBP or heart rate. Stratifying by baseline SBP, a differential response was demonstrated: SBP increased in the 2 lowest strata (<100 mm Hg and 101-110 mm Hg) and decreased in the remaining strata (P < .001). Stratified differences were sustained after individual EECP sessions, at the end of the course of EECP, and 6 weeks after the final EECP session and were independent of changes in cardiovascular medications. CONCLUSIONS: Enhanced external counterpulsation improved SBP in patients with refractory angina. On average, EECP decreased SBP during treatment and follow-up; but for patients with low baseline SBP (<110 mm Hg), EECP increased SBP. The improvements in SBP may contribute to the clinical benefit of EECP.

Asunto(s)

Angina de Pecho/terapia , Presión Sanguínea/fisiología , Enfermedad Coronaria/terapia , Contrapulsación/métodos , Anciano , Angina de Pecho/fisiopatología , Comorbilidad , Enfermedad Coronaria/fisiopatología , Diástole/fisiología , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Sistólico/fisiología , Sístole/fisiología

RESUMEN

As coronary artery disease (CAD) continues to be the primary cause of mortality, a more in-depth understanding of pathophysiology and novel treatments are being sought. The past two decades have established inflammation as a driving force behind CAD--from endothelial dysfunction to heart failure. Recent advances in stem/progenitor cell biology have led to initial applications of progenitor cells in CAD continuum and have revealed that atherosclerosis is, at least in part, a disease of failed endogenous vascular repair. Several key progenitor cell populations including endothelial progenitor cells (AC133+/CD34+ population), vascular progenitors (CD31+/CD45(low) population), KDR+ cells and other bone marrow subtypes are mobilized for vascular repair. However, age and risk factors negatively impact these cells even prior to clinical CAD. Sex-based differences in progenitor cell capacity for repair have emerged as a new research focus that may offer mechanistic insights into clinical CAD discrepancies between men and women. Quantifying injury and cell-based repair and better defining their interactions should enable us to halt or even prevent CAD by enhancing the repair side of the repair/injury equation.

Asunto(s)

Aterosclerosis/fisiopatología , Antígenos CD/fisiología , Aterosclerosis/complicaciones , Enfermedad Coronaria/epidemiología , Fertilidad , Humanos , Células Madre/fisiología , Accidente Cerebrovascular/epidemiología , Cicatrización de Heridas

RESUMEN

The recently discovered therapeutic potential of stem or progenitor cells has initiated development of novel treatments in a number of diseases-treatments that could not only improve patients' quality of life, but also halt or even prevent disease progression. Hypertension; fluctuations in glycemia, electrolytes, nutrient levels, and circulating volume; and frequent infections and the associated inflammation all greatly impair the endothelium in patients undergoing peritoneal dialysis. As our understanding of the regulatory function of the endothelium advances, focus is increasingly being placed on endothelial repair in acute and chronic renal failure and after renal transplantation. The potential of progenitor cells to repair damaged endothelium and to reduce inflammation in patients with renal failure remains unexamined; however, a successful cell therapy could reduce morbidity and mortality in kidney disease. Important contributions have been made in identifying progenitor cell populations in the kidney, and further investigations into the relationships of these cells with the pathophysiology of the disease are underway. As the kidney disease field prepares for the first human trials of progenitor cell therapies, we deemed it important to review representative original research, and to share our perspectives and lessons learned from clinical trials of progenitor cell-based therapies that have commenced in patients with cardiovascular disease.

Asunto(s)

Diálisis Peritoneal , Insuficiencia Renal/terapia , Trasplante de Células Madre/métodos , Células Madre/fisiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/terapia , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Células Epiteliales/fisiología , Humanos , Inflamación , Riñón/citología , Trasplante de Riñón , Calidad de Vida , Insuficiencia Renal/complicaciones

RESUMEN

There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells (BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout (apoE(-/-)) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched (males, n=11; females, n=13) or -mismatched (males, n=12; females, n=14) BMNCs obtained from C57BL6/J mice. The rest of the apoE(-/-) mice were vehicle treated (males, n=13; females, n=20) or were age-matched untreated controls (males, n=9; females, n=10). Aortic plaque burden, progenitor cell profiles in bone marrow (BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE(-/-) recipients significantly decreased plaque formation (P<0.001). This reparative response univariately correlated with increased CD34(+) (P=0.02), CD45(+) (P=0.0001), and AC133(+)/CD34(+) (P=0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31(+)/CD45(low) cells. In a multivariate analysis, BM-AC133(+)/CD34(+) and BM-CD45(+) percentage counts correlated with a lower plaque burden (P<0.05). Increased granulocyte colony-stimulating factor levels highly correlated with plaque attenuation (r=-0.86, P=0.0004). In untreated apoE(-/-) mice of either sex, BM-AC133(+)/CD34(+) cells rose initially and then fell as plaque accumulated; however, BM-AC133(+)/CD34(+) percentages were higher in females at all times (P

Asunto(s)

Trasplante de Médula Ósea , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Leucocitos Mononucleares/trasplante , Caracteres Sexuales , Animales , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Enfermedad de la Arteria Coronaria/patología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados

RESUMEN

The increasing longevity of patients with heart failure (HF) and the rise in the incidence of HF has created an urgent need to effectively treat and prevent left ventricular remodeling. Within the past 6 years, skeletal myoblast and bone marrow mononuclear cell transplantation have been undertaken in over 200 patients with HF, geared to the underlying injury, not just its mechanisms. Early safety/feasibility studies showed promising but somewhat conflicting secondary symptomatic and functional improvements, and safety concerns have arisen. However, the patient population, cell type, dose, time, mode of delivery, and outcome measures differed-making comparisons problematic. It is now time to: 1) create a central registry of all patients treated with cells; 2) perform side-by-side comparisons of different types of cells in patients with similar HF states; 3) agree on standardized trial designs; and 4) define acceptable and unacceptable outcomes (and measures) compared with both standard of care and to other emerging therapies. By doing so, we can avoid the pitfalls that previous biologics (eg, angiogenic gene therapy) have suffered, increase the likelihood of success, shorten the time-to-presentation of cell-based algorithms to clinicians, and deliver these therapies to patients who await new ways of reduction of symptoms and improvement of quality of life.

Asunto(s)

Trasplante de Médula Ósea , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Mioblastos Esqueléticos/trasplante , Remodelación Ventricular , Ensayos Clínicos como Asunto , Insuficiencia Cardíaca/cirugía , Humanos , Proyectos de Investigación , Volumen Sistólico

RESUMEN

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. METHODS AND RESULTS: We prospectively analyzed 320 consecutive HCM patients (age, 47+/-17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients > or = 50 mm Hg and were not exercised. Of the other 201 patients with gradients < 50 mm Hg at rest (average, 4+/-9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve-septal contact after exercise (80+/-43 mm Hg), including 76 with marked gradients > or = 50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (< 30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction. CONCLUSIONS: Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%). Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy. Assessment of subaortic gradients with exercise should be a routine component of the evaluation of HCM patients without outflow obstruction under resting conditions.

Asunto(s)

Cardiomiopatía Hipertrófica/complicaciones , Obstrucción del Flujo Ventricular Externo/epidemiología , Obstrucción del Flujo Ventricular Externo/fisiopatología , Adulto , Anciano de 80 o más Años , Gasto Cardíaco Bajo/diagnóstico , Gasto Cardíaco Bajo/etiología , Ecocardiografía de Estrés , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Maniobra de Valsalva , Obstrucción del Flujo Ventricular Externo/diagnóstico , Obstrucción del Flujo Ventricular Externo/etiología

RESUMEN

BACKGROUND: End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. METHODS AND RESULTS: Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients < or = 40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3+/-3 years. Duration from onset of HCM symptoms to ES identification was considerable (14+/-10 years), but ES onset to death/transplantation was brief (2.7+/-2 years). ES occurred with similar frequency in patients with or without prior myectomy (P=0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. CONCLUSIONS: ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.

Asunto(s)

Cardiomiopatía Hipertrófica/epidemiología , Cardiomiopatía Hipertrófica/fisiopatología , Remodelación Ventricular/fisiología , Adolescente , Adulto , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/patología , Niño , Estudios de Cohortes , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Prevalencia , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos/epidemiología

RESUMEN

OBJECTIVES: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. METHODS: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12-18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion.

Asunto(s)

Estenosis de la Válvula Aórtica/prevención & control , Braquiterapia , Cateterismo , Anciano de 80 o más Años , Aorta/efectos de la radiación , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/terapia , Terapia Combinada , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Radioterapia/métodos , Dosificación Radioterapéutica , Recurrencia

RESUMEN

BACKGROUND: Genetic mutations are the most common cause of hypertrophic cardiomyopathy (HCM) and an increasingly recognized cause of dilated cardiomyopathy. Autosomal dominant HCM is caused by mutations in sarcomere proteins; such mutations are not universally present, however, and fail to account for &40% of cases of phenotypic HCM. To add further complexity, other genetic origins can mimic the gross clinical phenotype of HCM, and mutations in sarcomere genes have been demonstrated to cause dilated cardiomyopathy. METHODS AND RESULTS: To explore novel genetic causes of inherited cardiomyopathies, genome-wide linkage analysis was used to study one kindred (4 generations, 32 individuals) with predominant clinical features of left ventricular hypertrophy in addition to cardiac dilation, end-stage heart failure, and sudden death. Of note, histopathology from 2 family members did not demonstrate myocyte disarray and fibrosis, indicating that this phenotype is not typical sarcomere mutation HCM. Direct DNA sequencing was performed on sarcomere genes known to cause HCM and dilated cardiomyopathy, and no mutations were identified. Linkage was then established to a novel locus on chromosome 7 (7p12.1-7q21). A maximum 2-point logarithm of odds score of 4.11 was obtained. Recombination events refine the disease interval between D7S506 and D7S3314, corresponding to a distance of 27.2 megabases. CONCLUSIONS: The discovery of a novel genetic locus in this family provides more evidence that molecular pathways leading to inherited cardiac hypertrophy extend beyond the sarcomere. Identification of the causal gene mutation and additional genotype-phenotype correlation studies will provide fundamental insight into mechanisms of cardiac remodeling.

Asunto(s)

Cardiomiopatía Dilatada/genética , Cardiomiopatía Hipertrófica/genética , Cromosomas Humanos Par 7/genética , Alelos , Cardiomiopatía Dilatada/patología , Cardiomiopatía Hipertrófica/patología , Mapeo Cromosómico , Proteínas Contráctiles/genética , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Haplotipos/genética , Humanos , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/patología , Escala de Lod , Masculino , Linaje , Sarcómeros/metabolismo , Análisis de Secuencia de ADN , Secuencias Repetidas en Tándem

RESUMEN

Left ventricular apical aneurysms, in absence of coronary artery disease, occur in approximately 1% of patients with hypertrophic cardiomyopathy (HC). Identical twins, age 44 years, are presented with HC and identical LV morphology, including apical aneurysms. These cases demonstrate a genetic predisposition to the development of apical aneurysm, as well as overall LV morphology, in patients with HC.

Asunto(s)

Cardiomiopatía Hipertrófica/complicaciones , Enfermedades en Gemelos , Aneurisma Cardíaco/complicaciones , Gemelos Monocigóticos , Adulto , Cardiomiopatía Hipertrófica/patología , Cardiomiopatía Hipertrófica/fisiopatología , Femenino , Aneurisma Cardíaco/patología , Aneurisma Cardíaco/fisiopatología , Ventrículos Cardíacos , Humanos

Asunto(s)

Traumatismos en Atletas/complicaciones , Reanimación Cardiopulmonar , Muerte Súbita Cardíaca/etiología , Desfibriladores , Fibrilación Ventricular/etiología , Fibrilación Ventricular/terapia , Adulto , Ecocardiografía , Electrocardiografía , Resultado Fatal , Humanos , Masculino , Traumatismos Torácicos/complicaciones , Insuficiencia del Tratamiento , Fibrilación Ventricular/diagnóstico

RESUMEN

BACKGROUND: Two-dimensional echocardiography is currently the standard test for the clinical diagnosis of hypertrophic cardiomyopathy (HCM). The present study was undertaken to determine whether cardiac MRI (CMR) affords greater accuracy than echocardiography in establishing the diagnosis and assessing the magnitude of left ventricular (LV) hypertrophy in HCM. METHODS AND RESULTS: Forty-eight patients (age 34+/-16 years) suspected of having HCM (or with a confirmed diagnosis) were imaged by both echocardiography and CMR to assess LV wall thickness in 8 anatomic segments (total n=384 segments) and compared in a blinded fashion. Maximum LV thickness was similar by echocardiography (21.7+/-9.1 mm) and CMR (22.5+/-9.6 mm; P=0.21). However, in 3 (6%) of the 48 patients, echocardiography did not demonstrate LV hypertrophy, and CMR identified otherwise undetected areas of wall thickening in the anterolateral LV free wall (17 to 20 mm), which resulted in a new diagnosis of HCM. In the overall study group, compared with CMR, echocardiography also underestimated the magnitude of hypertrophy in the basal anterolateral free wall (by 20+/-6%; P=0.001), as well as the presence of extreme LV wall thickness (> or =30 mm) in 10% of patients (P<0.05). CONCLUSIONS: CMR is capable of identifying regions of LV hypertrophy not readily recognized by echocardiography and was solely responsible for diagnosis of the HCM phenotype in an important minority of patients. CMR enhances the assessment of LV hypertrophy, particularly in the anterolateral LV free wall, and represents a powerful supplemental imaging test with distinct diagnostic advantages for selected HCM patients.

Asunto(s)

Cardiomiopatía Hipertrófica/diagnóstico , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Niño , Ecocardiografía , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Disfunción Ventricular Izquierda/patología

RESUMEN

Twelve-lead electrocardiography, a traditional component in evaluations of patients with hypertrophic cardiomyopathy (HC), is often regarded as a marker for the magnitude of left ventricular (LV) hypertrophy, which in turn has been linked to sudden death risk. To determine whether electrocardiographic (ECG) patterns have clinical utility by accurately reflecting phenotypic expression or predicting clinical outcome, voltages and patterns were compared with LV wall thicknesses assessed by echocardiography and with clinical outcomes in 448 consecutive patients with HC. Significant but relatively weak correlations were evident between maximum LV wall thickness and ECG voltage: r = 0.295 (p <0.01) for the sum of R- and S-wave voltages in all 12 leads, r = 0.254 (p <0.01) for the maximum R or S wave in any lead, and r = 0.210 (p <0.01) for the sum of SV(1) (or SV(2)) and RV(5) (or RV(6)). Of 55 patients with extreme LV hypertrophy (LV wall thickness > or =30 mm), only 24 (44%) showed greatly increased ECG voltage > or =30 mm in any lead. Of 102 patients with outflow gradients > or =30 mm Hg at rest, only 43 (42%) had ECG voltage > or =30 mm in any lead. Normal ECG results were uncommonly associated with HC-related death (1 of 40 patients, 2.5%) but had similar prevalence in surviving patients (17 of 376 patients, 4.5%; p = NS). In conclusion, in HC, 12-lead ECG voltages are not a reliable clinical marker for the magnitude of LV hypertrophy or outflow obstruction. Diverse ECG patterns, consistent with heterogeneous expression of this disease, did not predict HC-related death. Scalar electrocardiography has selective but limited power in routine clinical assessments of patients with HC.

Asunto(s)

Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Muerte Súbita Cardíaca , Electrocardiografía , Regulación de la Expresión Génica , Adulto , Anciano , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/mortalidad , Estudios de Cohortes , Ecocardiografía Doppler , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Probabilidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia

RESUMEN

In hypertrophic cardiomyopathy (HC), an important subgroup of patients develop progressive and disabling symptoms that are related to heart failure and death. Although a direct relation has been demonstrated between left ventricular (LV) wall thickness and likelihood of sudden and unexpected death (usually in patients who are asymptomatic or mildly symptomatic), it is unresolved whether magnitude of hypertrophy is similarly associated with severity of heart failure. To determine the relation of LV wall thickness to heart failure symptoms in HC, 700 consecutive patients who had HC were assessed by 2-dimensional echocardiography. The relation between maximum level of heart failure symptoms by New York Heart Association functional class and maximum LV wall thickness was not linear but rather parabolic. Therefore, marked symptoms were most commonly associated with moderate degrees of LV hypertrophy (wall thickness 16 to 24 mm; 27%) but less frequently with extreme hypertrophy (>/=30 mm 13%) or mild hypertrophy (

Asunto(s)

Cardiomiopatía Hipertrófica/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cardiomiopatía Hipertrófica/complicaciones , Niño , Preescolar , Ecocardiografía , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertrofia Ventricular Izquierda/complicaciones , Lactante , Masculino , Persona de Mediana Edad , Análisis de Regresión

RESUMEN

OBJECTIVES: The goal of this study was to assemble a profile and assess the significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy (HCM) cohort. BACKGROUND: Hypertrophic cardiomyopathy is associated with arrhythmia-related consequences, particularly sudden death. Ventricular tachyarrhythmias on Holter electrocardiograms (ECG) have been reported as markers for sudden death in highly selected HCM populations. METHODS: We assessed the profile of ventricular and supraventricular ectopy and bradyarrhythmia on ambulatory 24-h Holter ECG and also related these findings to clinical outcome in 178 HCM patients. RESULTS: Of the 178 study patients, 157 (88%) had premature ventricular complexes (PVCs), including 21 (12%) with >/=500 PVCs, 74 (42%) had couplets, 67 (37%) had supraventricular tachycardia (SVT), and 56 (31%) had nonsustained ventricular tachycardia (NSVT). Mean number of PVCs was 330 +/- 763 (range 1 to 5,435) and increased with age (p < 0.01); NSVT was associated with greater left ventricular hypertrophy (p = 0.01) and severe symptoms (New York Heart Association functional classes III and IV) (p = 0.04); SVT occurred more commonly in patients with outflow obstruction (p = 0.02). Over a follow-up of 5.5 +/- 3.4 years, 11 (6%) patients died suddenly (annual mortality rate, 1.1%) including 5 patients with NSVT. For sudden death, NSVT on Holter ECG had negative and positive predictive values of 95% and 9%, and sensitivity and specificity of 45% and 69%, respectively. CONCLUSIONS: In this nontertiary-based HCM cohort, ventricular and supraventricular tachyarrhythmias were particularly frequent and demonstrated a broad spectrum on ambulatory (Holter) ECG. Paradoxically, despite such a highly arrhythmogenic substrate, sudden death events proved to be relatively uncommon. Ventricular tachyarrhythmias had a low positive and relatively high negative predictive value for sudden death in this HCM population.

Asunto(s)

Bradicardia/epidemiología , Cardiomiopatía Hipertrófica/epidemiología , Electrocardiografía Ambulatoria , Taquicardia Supraventricular/epidemiología , Taquicardia Ventricular/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Complejos Atriales Prematuros/diagnóstico , Complejos Atriales Prematuros/epidemiología , Bradicardia/diagnóstico , Servicio de Cardiología en Hospital , Cardiomiopatía Hipertrófica/diagnóstico , Niño , Preescolar , Comorbilidad , Muerte Súbita Cardíaca/epidemiología , Femenino , Estudios de Seguimiento , Hospitales Comunitarios , Humanos , Masculino , Persona de Mediana Edad , Minnesota , Factores de Riesgo , Análisis de Supervivencia , Taquicardia Supraventricular/diagnóstico , Taquicardia Ventricular/diagnóstico , Complejos Prematuros Ventriculares/diagnóstico , Complejos Prematuros Ventriculares/epidemiología

RESUMEN

BACKGROUND: A clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction and triggered by psychological stress is emerging, with reports largely confined to Japan. METHODS AND RESULTS: Over a 32-month period, 22 consecutive patients with this novel cardiomyopathy were prospectively identified within a community-based practice in the Minneapolis-St. Paul, Minn, area. All patients were women aged 32 to 89 years old (mean 65+/-13 years); 21 (96%) were > or =50 years of age. The syndrome is characterized by (1) acute substernal chest pain with ST-segment elevation and/or T-wave inversion; (2) absence of significant coronary arterial narrowing by angiography; (3) systolic dysfunction (ejection fraction 29+/-9%), with abnormal wall motion of the mid and distal LV, ie, "apical ballooning"; and (4) profound psychological stress (eg, death of relatives, domestic abuse, arguments, catastrophic medical diagnoses, devastating financial or gambling losses) immediately preceding and triggering the cardiac events. A significant proportion of patients (37%) had hemodynamic compromise and required vasopressor agents and intra-aortic balloon counterpulsation. Each patient survived with normalized ejection fraction (63+/-6%; P<0.001) and rapid restoration to previous functional cardiovascular status within 6+/-3 days. In 95%, MRI identified diffusely distributed segmental wall-motion abnormalities that encompassed LV myocardium in multiple coronary arterial vascular territories. CONCLUSIONS: A reversible cardiomyopathy triggered by psychologically stressful events occurs in older women and may mimic evolving acute myocardial infarction or coronary syndrome. This condition is characterized by a distinctive form of systolic dysfunction that predominantly affects the distal LV chamber and a favorable outcome with appropriate medical therapy.

Asunto(s)

Cardiomiopatía Dilatada/epidemiología , Estrés Psicológico/complicaciones , Disfunción Ventricular Izquierda/epidemiología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/etiología , Dolor en el Pecho/etiología , Estudios de Cohortes , Angiografía Coronaria , Diagnóstico Diferencial , Electrocardiografía , Femenino , Ventrículos Cardíacos/patología , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Minnesota/epidemiología , Infarto del Miocardio/diagnóstico , Pronóstico , Estudios Prospectivos , Estrés Psicológico/fisiopatología , Volumen Sistólico , Síndrome , Troponina I/sangre , Troponina T/sangre , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiología

Asunto(s)

Cardiomiopatía Hipertrófica/complicaciones , Aneurisma Coronario/etiología , Anciano , Medios de Contraste , Gadolinio , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND: Hypertrophic cardiomyopathy (HCM) has a diverse clinical spectrum that often includes progressive heart failure symptoms and disability. Assessment of symptom severity may be highly subjective, encumbered by the heterogeneous clinical presentation. Plasma B-type natriuretic peptide (BNP) has been used widely as an objective marker for heart failure severity and outcome, predominantly in coronary heart disease with ventricular dilatation and systolic dysfunction. METHODS AND RESULTS: We prospectively assessed plasma BNP as a quantitative clinical marker of heart failure severity in 107 consecutive HCM patients. BNP showed a statistically significant relationship to magnitude of functional limitation, assessed by New York Heart Association (NYHA) functional class: I, 136+/-159 pg/mL; II, 338+/-439 pg/mL; and III/IV, 481+/-334 pg/mL (P<0.001). Multivariable analysis showed that BNP was independently related to NYHA class as well as age and left ventricular wall thickness (each with a value of P=0.0001). BNP > or =200 pg/mL was the most reliable predictor of heart failure symptoms, with positive and negative predictive values of 63% and 79%, respectively. BNP power in distinguishing patients with or without heart failure symptoms was less than that for differentiating between no (or only mild) and severe symptoms (area under receiver operating characteristic curve=0.75 and 0.83, respectively). CONCLUSIONS: Plasma BNP is independently related to the presence and magnitude of heart failure symptoms in patients with HCM. As a clinical marker for heart failure, BNP is limited by considerable overlap in values between categories of heart failure severity as well as confounding variables of left ventricular wall thickness and age.

Asunto(s)

Cardiomiopatía Hipertrófica/sangre , Péptido Natriurético Encefálico/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/patología , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Ultrasonografía

RESUMEN

Research in biology and applications of growth factors in coronary artery disease (CAD) has progressed considerably over recent years. Vascular endothelial growth factor and fibroblast growth factor-2 have been more successful in animal models of myocardial ischemia and Phase I studies than in placebo-controlled trials. However, cardiac magnetic resonance (CMR), with its higher sensitivity and specificity indices for identification of CAD, has not been extensively used in trials of angiogenic therapies. Data in animals and in patients suggest that CMR can reliably identify collateral vessels. Therefore, we hypothesize that CMR may depict collateralization induced by angiogenic therapy better than currently used nuclear perfusion imaging modalities. Versatility of the assessment of myocardial function and perfusion in one imaging session, combined with the noninvasive nature of the test, may considerably lower the cost of clinical trials. Use of CMR-derived surrogate end points may provide better risk stratification and assessment of efficacy in patients receiving growth factor therapy.