title: Cardiopulmonary responses and prognosis in hypertrophic cardiomyopathy: a potential role for comprehensive noninvasive hemodynamic assessment.
abstract: OBJECTIVE
  This study sought to discover the key determinants of exercise capacity, maximal oxygen consumption (oxygen uptake [Vo2]), and ventilatory efficiency (ventilation/carbon dioxide output [VE/Vco2] slope) and assess the prognostic potential of metabolic exercise testing in hypertrophic cardiomyopathy (HCM).
  
  
  BACKGROUND
  The intrinsic mechanisms leading to reduced functional tolerance in HCM are unclear.
  
  
  METHODS
  The study sample included 156 HCM patients consecutively enrolled from January 1, 2007 to January 1, 2012 with a complete clinical assessment, including rest and stress echocardiography and cardiopulmonary exercise test (CPET) with impedance cardiography. Patients were also followed for the composite outcome of cardiac-related death, heart transplant, and functional deterioration leading to septal reduction therapy (myectomy or septal alcohol ablation).
  
  
  RESULTS
  Abnormalities in CPET responses were frequent, with 39% (n = 61) of the sample showing a reduced exercise tolerance (Vo2 max <80% of predicted) and 19% (n = 30) characterized by impaired ventilatory efficiency (VE/Vco2 slope >34). The variables most strongly associated with exercise capacity (expressed in metabolic equivalents), were peak cardiac index (r = 0.51, p < 0.001), age (r = -0.25, p < 0.01), male sex (r = 0.24, p = 0.02), and indexed right ventricular end-diastolic area (r = 0.31, p = 0.002), resulting in an R(2) of 0.51, p < 0.001. Peak cardiac index was the main predictor of peak Vo2 (r = 0.61, p < 0.001). The variables most strongly related to VE/VCO2 slope were E/E' (r = 0.23, p = 0.021) and indexed left atrial volume index (LAVI) (r = 0.34, p = 0.005) (model R(2) = 0.15). The composite endpoint occurred in 21 (13%) patients. In an exploratory analysis, 3 variables were independently associated with the composite outcome (mean follow-up 27 ± 11 months): peak Vo2 <80% of predicted (hazard ratio: 4.11; 95% confidence interval [CI]: 1.46 to 11.59; p = 0.008), VE/Vco2 slope >34 (hazard ratio: 3.14; 95% CI: 1.26 to 7.87; p = 0.014), and LAVI >40 ml/m(2) (hazard ratio: 3.32; 95% CI: 1.08 to 10.16; p = 0.036).
  
  
  CONCLUSIONS
  In HCM, peak cardiac index is the main determinant of exercise capacity, but it is not significantly related to ventilatory efficiency. Peak Vo2, ventilatory inefficiency, and LAVI are associated with an increased risk of major events in the short-term follow-up.
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California; St. George's University of London, London, United Kingdom. Electronic address: gherardobis@yahoo.it.
authors: Gherardo
authors: G
authors: Finocchiaro
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford, California.
authors: Francois
authors: F
authors: Haddad
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford, California.
authors: Joshua W
authors: JW
authors: Knowles
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California.
authors: Colleen
authors: C
authors: Caleshu
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California.
authors: Aleksandra
authors: A
authors: Pavlovic
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California.
authors: Julian
authors: J
authors: Homburger
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California.
authors: Yael
authors: Y
authors: Shmargad
authors: Cardiovascular Department, Ospedali Riuniti and University of Trieste, Italy.
authors: Gianfranco
authors: G
authors: Sinagra
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California.
authors: Emma
authors: E
authors: Magavern
authors: Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors: Myo
authors: M
authors: Wong
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California.
authors: Marco
authors: M
authors: Perez
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford, California.
authors: Ingela
authors: I
authors: Schnittger
authors: Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors: Jonathan
authors: J
authors: Myers
authors: Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors: Victor
authors: V
authors: Froelicher
authors: Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford, California. Electronic address: euan@stanford.edu.
authors: Euan A
authors: EA
authors: Ashley
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000503:physiopathology*; D018450:Disease Progression; D015150:Echocardiography, Doppler; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology*; D011379:Prognosis
keywords: cardiopulmonary test; echocardiography; heart failure; hypertrophic cardiomyopathy