Hector R. Villarraga

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncologic therapeutic armamentarium. Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction. Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ven- tricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and spe- cific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat ma- lignancies, the invasive nature of the procedure, and the remarkable progress made in noninvasive cardiac imaging. The noninvasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially car- diotoxic cancer treatment.

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

### A. Definition, classification, and mechanisms of toxicity Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncological therapeutic armamentarium.1 Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction.2 Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ventricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and specific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat malignancies, the invasive nature of the procedure, and the remarkable progress made in non-invasive cardiac imaging. The non-invasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially cardiotoxic cancer treatment.3–5 The timing of LV dysfunction can vary among agents. In the case of anthracyclines, the damage occurs immediately after the exposure;6 for others, the time frame between drug administration and detectable cardiac dysfunction appears to be more variable. Nevertheless, the heart has significant cardiac reserve, and the expression of damage in the form of alterations in systolic or diastolic parameters may not be overt until a substantial amount of cardiac reserve has been exhausted. Thus, cardiac damage may not become apparent until years or even decades after receiving the cardiotoxic treatment. This is particularly applicable to …

Right Ventricular Strain for Prediction of Survival in Patients With Pulmonary Arterial Hypertension

BACKGROUND Pulmonary arterial hypertension (PAH) is a devastating illness of pulmonary vascular remodeling, right-sided heart failure, and limited survival. Whether strain-based measures of right ventricular (RV) systolic function predict future right-sided heart failure and/or death is untested. METHODS RV longitudinal systolic strain and strain rate were evaluated by echocardiography in 80 patients with World Health Organization group 1 pulmonary hypertension (PH) (72% were functional class [FC] III or IV). Survival status was assessed over 4 years. RESULTS All patients had a depressed RV systolic strain (-15% ± 5%) and strain rate (-0.80 ± 0.29 s(-1)). Of the parameters assessed, average RV free wall systolic strain worse than -12.5% identified a cohort with greater severity of disease (82% were FC III/IV), greater RV systolic dysfunction (RV stroke volume index 26 ± 9 mL/m(2)), and higher right atrial pressure (12 ± 5 mm Hg). Patients with an RV free wall strain worse than -12.5% were associated with a greater degree of disease progression within 6 months, a greater requirement for loop diuretics, and/or a greater degree of lower extremity edema, and it also predicted 1-, 2-, 3-, and 4-year mortality (unadjusted 1-year hazard ratio, 6.2; 2.1-22.3). After adjusting for age, sex, PH cause, and FC, patients had a 2.9-fold higher rate of death per 5% absolute decline in RV free wall strain at 1 year. CONCLUSIONS Noninvasive assessment of RV longitudinal systolic strain and strain rate independently predicts future right-sided heart failure, clinical deterioration, and mortality in patients with PAH.

Dynamic Changes of Left Ventricular Performance and Left Atrial Volume Induced by the Mueller Maneuver in Healthy Young Adults and Implications for Obstructive Sleep Apnea, Atrial Fibrillation, and Heart Failure

Using the Mueller maneuver (MM) to simulate obstructive sleep apnea (OSA), our aim was to investigate acute changes in left-sided cardiac morphologic characteristics and function which might develop with apneas occurring during sleep. Strong evidence supports a relation between OSA and both atrial fibrillation and heart failure. However, acute effects of airway obstruction on cardiac structure and function have not been well defined. In addition, it is unclear how OSA might contribute to the development of atrial fibrillation and heart failure. Echocardiography was used in healthy young adults to measure various parameters of cardiac structure and function. Subjects were studied at baseline, during, and immediately after performance of the MM and after a 10-minute recovery. Continuous heart rate, blood pressure, and pulse oximetry measurements were made. During the MM, left atrial (LA) volume index markedly decreased. Left ventricular (LV) end-systolic dimension increased in association with a decrease in LV ejection fraction. On release of the maneuver, there was a compensatory increase in blood flow to the left side of the heart, with stroke volume, ejection fraction, and cardiac output exceeding baseline. After 10 minutes of recovery, all parameters returned to baseline. In conclusion, sudden imposition of severe negative intrathoracic pressure led to an abrupt decrease in LA volume and a decrease in LV systolic performance. These changes reflected an increase in LV afterload. Repeated swings in afterload burden and chamber volumes may have implications for the future development of atrial fibrillation and heart failure.

Evaluation and management of patients with heart disease and cancer: cardio-oncology.

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.

Role of Serial Quantitative Assessment of Right Ventricular Function by Strain in Pulmonary Arterial Hypertension

The aim of this study was to assess whether serial quantitative assessment of right ventricular (RV) function by speckle-based strain imaging is affected by pulmonary hypertension-specific therapies and whether there is a correlation between serial changes in RV strain and clinical status. RV longitudinal systolic function was assessed using speckle-tracking echocardiography in 50 patients with pulmonary arterial hypertension (PAH) before and after the initiation of therapy. The mean interval to follow-up was 6 ± 2 months. Subsequent survival was assessed over 4 years. Patients demonstrated a mean increase in RV systolic strain from -15 ± 5 before to -20 ± 7% (p = 0.0001) after PAH treatment. Persistence of or progression to a severe reduction in free wall systolic strain (<-12.5%) at 6 months was associated with greater disease severity (100% were in functional class III or IV vs 42%, p = 0.005), greater diuretic use (86% vs 40%, p = 0.02), higher mean pulmonary artery pressure (67 ± 20 vs 46 ± 17 mm Hg, p = 0.006), and poorer survival (4-year mortality 43% vs 23%, p = 0.002). After adjusting for age, functional class, and RV strain at baseline, patients with ≥ 5% improvement in RV free wall systolic strain had a greater than sevenfold lower mortality risk at 4 years (hazard ratio 0.13, 95% confidence interval 0.03 to 0.50, p = 0.003). In conclusion, serial echocardiographic assessment of RV longitudinal systolic function by quantitative strain imaging independently predicts clinical deterioration and mortality in patients with PAH after the institution of medical therapy.

Doppler Myocardial Imaging for Early Detection of Right Ventricular Dysfunction in Patients With Pulmonary Hypertension

BACKGROUND In pulmonary hypertension (PHT), right ventricular (RV) function affects treatment strategy and prognosis. Doppler myocardial imaging (DMI) has the potential to detect early RV dysfunction. METHODS Regional RV function was prospectively assessed in 110 patients without primary structural heart disease, including patients with known PHT (group I; n = 40; mean age, 59 +/- 16 years) and tricuspid regurgitation (TR) velocity >/= 3 m/s; group II (n = 30; mean age, 57 +/- 13 years), with TR velocity > 2.5 to < 3.0 m/s; and group III (n = 40; mean age, 56 +/- 9 years), with normal echocardiographic results and TR velocity </= 2.5 m/s. All underwent the assessment of RV function with the RV index of myocardial performance (RIMP), RV fractional area change, tricuspid annular plane systolic excursion, and DMI of the interventricular septum and RV free wall. RESULTS Basal RV peak systolic strain and strain rate (SR) were correlated with TR velocity (r = 0.59 and r = 0.49, respectively; P < .0001) and with RIMP (r = 0.53 and r = 0.45, respectively; P < .0001). Despite similar RV functional parameters in groups II and III, basal RV strain and SR and basal septal SR were significantly attenuated in group II (-27.8 +/- 5.1% vs -31.1 +/- 5.6%, P = .016; -1.6 +/- 0.4 vs -1.9 +/- 0.5 s(-1), P = .004; and -1.2 +/- 0.2 vs -1.4 +/- 0.1 s(-1), P < .001, respectively). Although 6 patients in group I had normal RIMP values, this subgroup had attenuated SR and strain compared with group III. CONCLUSIONS RV and septal systolic strain and SR may allow the recognition of early RV dysfunction in patients with PHT, even when conventional RV systolic parameters are normal.

Impaired Left Ventricular Mechanics in Pulmonary Arterial Hypertension: Identification of a Cohort at High Risk

Background— Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling and right heart failure. The right (RV) and left ventricles (LV) do not function in isolation, sharing a common pericardial sac and interventricular septum. We sought to define the clinical and prognostic significance of ventricular interdependence in PAH and its association with LV filling patterns through speckle-tracking strain echocardiography. Methods and Results— Echocardiography was performed in 71 adults with a new diagnosis of PAH. To analyze LV and RV function separately, we measured peak systolic longitudinal and circumferential strain of the LV and RV. Survival was assessed >2 years. Patients had dilated right-sided chambers (right atrial volume index, 44±19 mL/m2; RV end-diastolic area, 34±9 cm2), and reduced RV function (RV fractional area change, 28±12%). Speckle-tracking echocardiography revealed significant reductions in RV free wall peak systolic strain (−15±3%). Despite normal LV size and normal conventional measures of LV systolic function (end-diastolic dimension, 42±6 mm; ejection fraction, 65±8%; cardiac index, 2.6±0.8 L/min per m2), patients had reduced LV free wall systolic strain (−15±3%). Decreased LV free wall systolic strain was associated with a delayed relaxation mitral inflow Doppler pattern, P =0.0002. During 2-year follow-up, 19 patients (27%) died. LV strain was associated with increased mortality (unadjusted hazard ratio, 2.40 per 5% decrease in LV free wall strain, 1.22–4.68), which remained significant when adjusted for age, sex, World Health Organization functional class, and PAH pathogenesis (hazard ratio, 3.11, 1.38–7.20). Conclusions— The pressure loading in PAH results in geometric alterations and functional decline of the RV, with marked reduction in RV systolic strain. Despite preservation of LV ejection fraction, LV systolic strain was also reduced and associated with early mortality, highlighting the significance of ventricular interdependence in PAH.Background—Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling and right heart failure. The right (RV) and left ventricles (LV) do not function in isolation, sharing a common pericardial sac and interventricular septum. We sought to define the clinical and prognostic significance of ventricular interdependence in PAH and its association with LV filling patterns through speckle-tracking strain echocardiography. Methods and Results—Echocardiography was performed in 71 adults with a new diagnosis of PAH. To analyze LV and RV function separately, we measured peak systolic longitudinal and circumferential strain of the LV and RV. Survival was assessed >2 years. Patients had dilated right-sided chambers (right atrial volume index, 44±19 mL/m2; RV end-diastolic area, 34±9 cm2), and reduced RV function (RV fractional area change, 28±12%). Speckle-tracking echocardiography revealed significant reductions in RV free wall peak systolic strain (−15±3%). Despite normal LV size and normal conventional measures of LV systolic function (end-diastolic dimension, 42±6 mm; ejection fraction, 65±8%; cardiac index, 2.6±0.8 L/min per m2), patients had reduced LV free wall systolic strain (−15±3%). Decreased LV free wall systolic strain was associated with a delayed relaxation mitral inflow Doppler pattern, P=0.0002. During 2-year follow-up, 19 patients (27%) died. LV strain was associated with increased mortality (unadjusted hazard ratio, 2.40 per 5% decrease in LV free wall strain, 1.22–4.68), which remained significant when adjusted for age, sex, World Health Organization functional class, and PAH pathogenesis (hazard ratio, 3.11, 1.38–7.20). Conclusions—The pressure loading in PAH results in geometric alterations and functional decline of the RV, with marked reduction in RV systolic strain. Despite preservation of LV ejection fraction, LV systolic strain was also reduced and associated with early mortality, highlighting the significance of ventricular interdependence in PAH.

Ultrasound Assessment of the Displacement and Deformation of the Median Nerve in the Human Carpal Tunnel with Active Finger Motion

BACKGROUND Peripheral nerves are mobile structures, stretching and translating in response to changes in the position of adjuvant anatomic structures. The objective of this study was to develop a novel method to characterize the relative motion and deformation of the median nerve on cross-sectional ultrasound images of the carpal tunnel during active finger motion. METHODS Fifteen volunteers without a history of carpal tunnel syndrome or wrist trauma were recruited. An ultrasound scanner and a linear array transducer were used to evaluate the motion of the median nerve and the flexor tendons within the carpal tunnel during motion from full extension to full flexion by the four fingers (fist motion) and by the long finger alone. The displacement of the median nerve relative to the long-finger flexor digitorum superficialis tendon as well as the perimeter, cross-sectional area, circularity, and aspect ratio of a minimum enclosing rectangle of the median nerve were measured. The data were compared between single-digit motion and fist motion and between extension and flexion positions. RESULTS The distance between the long-finger flexor digitorum superficialis tendon and the median nerve with isolated long-finger flexion was decreased in the ulnar-radial direction and increased in the palmar-dorsal direction as compared with the distance with four-finger flexion (p < 0.01). Compared with the values with fist motion, the aspect ratio was decreased and the circularity was increased with long-finger motion (p < 0.01). CONCLUSIONS This report presents a method with which to assess displacement and deformation of the median nerve on a cross-sectional ultrasound image during different finger motions. This method may be useful to assess pathological changes within the carpal tunnel, and we plan to perform a similar study of patients with carpal tunnel syndrome on the basis of these preliminary data.

Normal left ventricular mechanical function and synchrony values by speckle-tracking echocardiography in the transplanted heart with normal ejection fraction.

BACKGROUND The purpose of this study was to describe the normal values for strain (S), systolic strain rate (SRs) and synchrony by speckle-tracking echocardiography (STE) in heart transplant (HTx) recipients who had normal left ventricular ejection fraction (LVEF) and no clinically significant complications. METHODS We evaluated S and SRs in 40 HTx patients at 1 year after transplant and 82 healthy controls with STE using velocity vector imaging. RESULTS Mean (SD) global longitudinal S and SRs, respectively, were lower in the transplant group compared with controls [-13.43% (2.39%) vs -17.28% (2.30%), p < 0.001; -0.83 (0.15) s(-1) vs -0.96 (0.13) s(-1), p < 0.001]. These variables were good for differentiating between groups: area under the curve was 0.88 for S and 0.73 for SRs. The differences remained significant after adjustment for other clinical variables. Global circumferential S and SRs were similar between groups. The standard deviation of the global longitudinal S time to peak of the 16 segments for HTx and control groups, respectively, was 41.67 (13.53) milliseconds vs 32.57 (12.81) milliseconds (p < 0.001). With 58.2 milliseconds as a cutoff value to define left ventricular synchrony, only 3 (8%) of the HTx patients and 4 (5%) of the control subjects were above that value (p = 0.6). CONCLUSION To our knowledge, this is the first study describing normal values for S and SRs and synchrony by STE in a HTx population with normal LVEF: longitudinal S and SRs were reduced; circumferential deformation indexes were normal; and left ventricular synchrony was preserved.